Thio-ether functionalized polymer and uses thereof

Abstract

Provided herein are thioether-functionalized cellulose polymers, compositions, films, fibers, particles, coatings, drug delivery articles, and methods of making and using the same. The polymers comprise a cellulose backbone of repeating anhydroglucose units and thioether substituents covalently attached to at least a portion of the hydroxyl groups of the repeating anhydroglucose units.

Description

Attorney Docket No. 701586-000154WOPTTHIO-ETHER FUNCTIONALIZED POLYMER AND USES THEREOFCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims benefit under 35 U. S. C. § 119(e) of U. S. Provisional Application 63 / 712,071 filed on October 25, 2024, the content of which is incorporated herein by reference in its entirety.TECHNICAL FIELD

[0002] The technology described herein relates to cellulose-based polymers and their use in medical, pharmaceutical, and industrial applications. More specifically, the technology described herein pertains to thioether-functionalized cellulose polymers and their oxidation-responsive properties, compositions, films, fibers, particles, coatings, drug delivery articles, and methods of preparation and use.GOVERNMENT SUPPORT

[0003] This invention was made with government support under Grant. No. F31NS135944 awarded by the National Institutes of Health (NIH). The government has certain rights in the invention.BACKGROUND

[0004] Cellulose-based materials have long been used in coatings, films, and industrial applications due to their natural abundance and renewable sourcing. Chemical modification of cellulose, particularly at the hydroxyl groups of the repeating anhydroglucose units, imparts new properties such as solubility in organic solvents, hydrophobicity, and processability. However, hydrophilic cellulose derivatives often suffer from swelling and delamination, limiting their use in medical device coatings and drug delivery systems. Thus, there remains a need for cellulose-based polymers with improved stability, biocompatibility, and responsive behavior to environmental stimuli, such as reactive oxygen species. The present disclosure addresses these needs.SUMMARY

[0005] In one aspect, provided herein are thioether-functionalized cellulose polymers comprising a cellulose backbone of repeating anhydroglucose units and thioether substituents covalently attached to at least a portion of the hydroxyl groups. The invention further provides compositions, films, fibers, particles, coatings, drug delivery articles, and methods of making and using the same. The polymers and articles described herein are oxidation-responsive, undergoing hydrophobic-to-hydrophilic transitions upon exposure to reactive oxygen species, and may be used in medical devices, drug delivery, antifouling surfaces, and controlled release systems.Attorney Docket No. 701586-000154WOPT

[0006] The cellulose polymer may be hydroxyethyl cellulose (HEC), methyl cellulose (MC), or hydroxy propyl methylcellulose (HPMC). In certain embodiments, the polymer is hydroxyethyl cellulose.

[0007] In some embodiments, the thioether-functionalized cellulose polymer is oxidation-responsive and undergoes a hydrophobic-to-hydrophilic transition upon exposure to a reactive oxygen species (ROS). At least a portion of the thioether substituents may be oxidized to sulfoxide or sulfone, alkylated to sulfonium ions, or converted to zwitterionic forms. The degree of modification may be at least 2.5 mol % of the hydroxyl groups, or from about 2.5 to about 95 mol%, or from about 5 to about 30 mol%. The polymer may comprise an average of about 0.5 to 2 thioether groups per anhydroglucose repeat unit, or about 0.63 thioether groups per repeat unit. The polymer may comprise from about 10 to about 100,000 anhydroglucose repeat units and have a molecular weight (MW) of from about 0.5 kDa to about 1,000 kDa, or from about 300 kDa to about 500 kDa. The polymer may have a polymer dispersion index (PDI) of from about 1 to about 5.

[0008] The polymer may be transparent or semi-transparent, thermally stable, hydrophobic or hydrophilic, and may have a water contact angle of about 50 degrees or higher, or about 40 degrees or lower. The polymer may be biocompatible, non-biodegradable or non-resorbable, biodegradable, non-immunogenic, antifouling, a copolymer, or a block polymer.

[0009] In another aspect, provided herein are compositions comprising a thioether-functionalized cellulose polymer described herein. The composition may further comprise a solvent, which may be a polar solvent, non-polar solvent, mixture of polar and non-polar solvents, protic solvent, aprotic solvent, organic solvent, aqueous solvent, green solvent, or halogenated solvent. The polymer may be present at a concentration of from about 0.01 to about 90% w / w or w / v, or from about 0.1 to about 50% w / w or w / v, or from about 0.5 to about 7.5% w / w or w / v. The composition may have a viscosity of from about 0.01 to about 250 Pa.s. The composition may further comprise a therapeutic agent.

[0010] In still another aspect, provided here are fdms comprising a thioether-functionalized cellulose polymer described herein. The film may have a thickness of from about 1 pm to about 150 pm, and an average surface roughness from about 5 nm to about 50 nm. The film may be antifouling, undergo a hydrophobic-to-hydrophilic transition at a surface region with minimal bulk swelling, and have a higher ultimate interfacial shear strength at failure relative to a film of a same cellulose polymer lacking the thioether substituents. The film may have an ultimate interfacial shear strength at failure of from 2000 kPa to 3500 kPa, an elastic modulus of from about 200 MPa to about 500 MPa in a dry state, an ultimate tensile strength of from about 20 MPa to about 50 MPa in a dry state, an elastic modulus of from about 500 MPa to about 750 MPa in a hydrated state, an ultimate tensile strength of from about 700 MPa to about 1,100 MPa in a hydratedAttorney Docket No. 701586-000154WOPTstate, and a surface elastic modulus of from about 200 kPa to about 700 kPa in an oxidized state. The fdm may be transparent or semi-transparent, have minimal fluorescent scattering, and further comprise a therapeutic agent. The therapeutic agent may be released from the fdm when the fdm undergoes a hydrophobic-to-hydrophilic transition or is exposed to a reactive oxygen species, and the release may be controlled or sustained. The fdm may be hydrophobic or hydrophilic, have a water contact angle of about 50 degrees or higher, or about 40 degrees or lower, be biocompatible, non-biodegradable or non-resorbable, biodegradable, non-immunogenic, antifouling, comprise two or more layers to form a multi-layered fdm, and be on a surface of a substrate, such as a medical device.

[0011] In yet another aspect, provided herein are fibers comprising a thioether-functionalized polymer described herein, wherein the fiber has a diameter between about 1 nm and 5 mm.

[0012] Also provided herein are particles comprising a thioether-functionalized cellulose polymer described herein, wherein the particle is a microparticle or a nanoparticle, and the polymer may be at a surface or in an interior of the particle. The particle may further comprise a therapeutic agent, which may be released from the particle when the particle undergoes a hydrophobic-to-hydrophilic transition or is exposed to a reactive oxygen species, and the release may be controlled or sustained. The particle may have a diameter of between about 1 nm and about 2 microns. The invention further provides polymeric meshes, foams, or hydrogels comprising a thioether-functionalized cellulose polymer described herein.

[0013] In yet still another aspect, provided herein is a substrate comprising a coating or film on at least a portion of a surface of the substrate, wherein the coating or film comprises a thioether-functionalized cellulose polymer described herein. The substrate may be a medical device, such as a catheter, pacemaker, drug infusion pump, implanted optical system, stent, vascular graft, neurostimulator, cochlear implant, orthopedic implant, cardiac lead, biosensor, artificial heart valve, implantable glucose monitor, or implantable drug depot. The coating or film may have a thickness from about 0.1 pm to about 150 pm, or from about 1 pm to about 75 pm, and an average surface roughness from about 5 nm to about 50 nm. The coating or film may comprise a therapeutic agent, be hydrophobic or hydrophilic, have a water contact angle of about 50 degrees or higher, or about 40 degrees or lower, be biocompatible, non-biodegradable or non-resorbable, non-immunogenic, and antifouling.

[0014] In still another aspect, provided herein is a drug-delivery article comprising a thioether-functionalized cellulose polymer described herein and a therapeutic agent. The drug delivery article may be in the form of a film, particle, mesh, fiber, gel, hydrogel, foam, mat, nonwoven mat, or any combinations thereof, and may be multilayered. The drug delivery article mayAttorney Docket No. 701586-000154WOPTcomprise a coating or film on a surface of a substrate, and the coating or film comprises the thioether-functionalized cellulose polymer. The thioether-functionalized cellulose polymer and the therapeutic agent may be in a mixture or present separately in the drug delivery article. The drugdelivery device may be cylindrical, circular, spherical, rectangular, cubic, polyhedron, prism, disc, or other geometric shape, or any combinations thereof, and may be in the form of an implant or an implantable device.

[0015] Also provided herein is a method for controlling the release of a therapeutic agent, comprising: (a) providing a drug-delivery article described herein; and (b) inducing a hydrophobic-to-hydrophilic transition in the thioether functionalized cellulose polymerYet, also provided herein is a method of forming a coating on a surface of a substrate, comprising applying a thioether-functionalized cellulose polymer described herein to at least a portion of a surface of the substrate. The coating step may comprise dip coating, spray coating, spin coating, drop casting, roll coating, or any combination thereof. The substrate may be a medical device. The polymer may be applied as a solution, and the method may further comprise removing a solvent from the solution after forming the coating or film, applying the solution to a mold and removing the solvent after applying to the mold, and removing the solvent by temperature and / or pressure-controlled vaporization. The method may further comprise drying the substrate after applying the polymer, under vacuum or at a temperature higher than room temperature. The coating or film may comprise a therapeutic agent. A method for preparing a thioether-functionalized cellulose polymer is also provided herein. The method comprises reacting a cellulose polymer with a thioether-functionalizing reagent, which may be an isothiocyanate-based thioether-functionalizing reagent, such as 3-(methylthio)propyl isothiocyanate. The cellulose polymer may be hydroxy ethyl cellulose (HEC), methyl cellulose (MC), or hydroxy propyl methylcellulose (HPMC), and the thioether-functionalized cellulose polymer may be described herein.BRIEF DESCRIPTION OF THE DRAWINGS

[0016] This patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.

[0017] FIGs. 1A-1H: Characterization of HECMTP polymers demonstrates control of physicochemical properties. FIG. 1A: Synthesis scheme for base-catalyzed, nucleophilic addition of MTPI to HEC to form HECMTP. FIG. IB: 'H NMR of HEC and HECMTP at 9, 16, and 21mol% functionality in dDMSO. FIG. 1C: FTIR of HEC and HECMTP at 9, 16, and 21mol% functionality highlighting MTP- associated peaks. FIG. ID: HEC and HECMTP at 9, 16, and 21mol% solubilized at 5wt% in PBS. FIG. IE: HECMTP can be oxidized to form HECso via the application of 1% H2O2Attorney Docket No. 701586-000154WOPTin water for 24hr. Resulting HECso solubilized at 5wt% in PBS. FIG. IF: 'H NMR in dTFA highlighting characteristic peaks associated with HEC, HECMTP and HECso. Labels in blue demarcate peak location. FIG. 1G: FTIR with characteristic absorption bands of chemical bonds in HEC, HECMTP and HECso. FIG. 1H: Contact angle data demonstrating a significant increase in hydrophobicity on the addition of the thioether moiety to HEC, and a subsequent, significant decrease in hydrophobicity upon oxidation of the thioether moiety (HECso). Inset: brightfield images from the goniometer demonstrating the deposition of deionized (DI) water on HEC, HECMTP and HECso films. Not significant (ns) and ***P< 0.0001 compared to HEC or as designated, one-way ANOVA with Tukey's multiple comparison test. Graph shows mean ± s.e.m. with individual data points showing n = 4 for HEC, n = 6 for HECMTP and HECso.

[0018] FIGs.2A-2J: HECMTP polymer can be formulated as coatings or films with tunable thickness. FIG.2A: Solubility table showing images of HECMTP polymer solubilized at lOmg / mL in DMSO and insoluble in MeOH, EtOH, IPA, acetone and water. FIG. 2B: Solubility table showing images of HECMTP polymer solubilized at lOmg / mL in a 50% / 50% solvent system of DMSO and MeOH, EtOH, IPA, or acetone, but precipitated in DMSO / water (50% / 50%). FIG.2C:Left: Dynamic rheological shear rate sweep measurements for HECMTP solubilized at 5wt% in a 100 / 0, 75 / 25, 50 / 50 DMSO / acetone solvent system showing viscosity (Pa.s) against increasing shear rate (s-1). Right: Box-and- whisker plot showing the increase in zero-shear viscosity (Pa.s), measured at a shear rate of 0.1 (s-1), with increasing concentration of acetone. Not significant (ns) and **P< 0.003 compared to 100 / 0 DMSO / Acetone or as designated. FIG. 2D: Left: Dynamic rheological shear rate sweep measurements for HECMTP at 1, 3, and 5wt% in DMSO showing viscosity (Pa.s) against increasing shear rate (s-1). Right: Box-and-whisker plot showing the increase in zero-shear viscosity (Pa.s), measured at a shear rate of 0.1 (s-1), with increasing concentration. ***P< 0.001 compared to lwt% or as designated. FIG. 2E: Brightfield image showing a HECMTP coating on a glass substrate. Black dashed lines outline the glass slide. White dashed lines outline the HECMTP-coated portion of the glass slide. FIG. 2F: Semi -log scatter plot showing the relationship between viscosity and coating thickness. Graph shows mean viscosity vs. mean coating thickness ± s.e.m. with individual data points showing n = 3 per group. The semi-log data line is fit with a linear line of best fit and the correlation is reported as Pearson’s Correlation Coefficient (r). FIG.2G: Bar graph showing effect of multiple dips of HECMTP solubilized at 5wt% in 100 / 0 DMSO / Acetone on coating thickness. *P<0.03, **P <0.003, and not significant (ns) compared to 1 dip or as designated. FIG.2H: Bar graph showing the effect of multiple dips on the average roughness of the coating. *P<0.04, and not significant (ns) compared to 1 dip or as designated. FIG. 21: Brightfield images showing the film-making process, including: the silicone mold, deposition of soluble HECMTP, and the resulting dried and punched HECMTP film. FIG. 2 J:Attorney Docket No. 701586-000154WOPTBar graph showing effect of multiple layers on film thickness using a 3wt% HECMTP solution in DMSO. *P < 0.02, ***p <0.0005 compared to 1 layer or as designated. All statistical comparisons were made using one-way ANOVAs with Tukey's multiple comparison tests. Graphs show mean ± s.e.m. with individual data points showing n = 3 per group.

[0019] FIGs 3A-3H: HECMTP coatings oxidize in response to H2O2 exposure but are impervious to dissolution in aqueous buffers. FIG. 3A: H2O2 remaining (pmol / cm2) following exposure of HEC, HECOCT, HECHEX, and HECMTP coatings to 4mM H2O2 for Id. **P <0.0015, ***P < 0.001, and not significant (ns) compared to HEC or as designated, one-way ANOVA with Tukey's multiple comparison test. Graph shows mean ± s.e.m. with individual data points showing n = 4 per group. FIG.3B: H2O2 remaining (pmol / cm2) after exposure of HECMTP coating to 4mM H2O2 for 1-168 hours (7d). ***P< 0.0007, each timepoint is compared with the previous timepoint, one-way ANOVA with Tukey's multiple comparison test. Graph shows mean ± s.e.m. with individual data points showing n = 8 for 24hrs, and n = 4 for all other groups. The line for t = 0 shows mean ± s.e.m., with s.e.m. represented as light shaded areas. FIG. 3C: pmol / cm2H2O2 consumed after exposure of HECMTP coatings to lOOpL of H2O2 at variable concentrations for Id. ***P< 0.0001 compared to 25 pmol / cm2H2O2 or as designated, one-way ANOVA with Tukey's multiple comparison test. Graph shows mean ± s.e.m. with individual data points showing n = 4 per group. FIG.3D: Exposure to increasing concentrations of H2O2 for 24 hrs leads to significant decreases in contact angle. *P<0.03, **P <0.004, ***P <0.001, and not significant (ns) with comparisons in pink being made to HECMTP (MTP) and comparisons in turquoise being made to HECso (SO), one-way ANOVA with Tukey's multiple comparison test. Graph shows mean ± s.e.m. with individual data points showing n = 6 for SO and n = 3 per group for all other conditions. Inset: brightfield images from the goniometer demonstrating the deposition of deionized water on HECMTP and HECMTP coatings treated with 40, 160, and 640pM of H2O2. FIG.3E: Contact angle measurements on HECMTP coatings over 7d exposed to either PBS or PBS + 80pM H2O2. ***P< 0.0001 comparisons between HECMTP and HECMTP + 80pM H2O2 at equivalent timepoints, two-way ANOVA with Tukey's multiple comparison test. Graph shows mean ± s.e.m., n = 3 per group. FIG.3F: Change in wet mass of HECHEX, HECOCT or HECMTP coatings over 7d exposed to either PBS or PBS + 80pM H2O2. *P<0.04, ***P <0.0005, and not significant (ns) comparisons are made between HECHEX or HECOCT with HECMTP at equivalent timepoints, two-way ANOVA with Tukey's multiple comparison test. Graph shows mean ± s.e.m., n = 4 for HECHEX and HECOCT and n = 3 for all other groups. FIG. 3G: %Change in dry mass of HECHEX, HECOCT or HECMTP coatings incubated in PBS or PBS + 80pM H2O2 over 7d. ***P< 0.0001, and not significant (ns) compared to HEC or as designated, one-way ANOVA with Tukey's multiple comparison test. Graph shows mean ± s.e.m. with individual data points showing n = 4 for HECHEX and HECOCT and n = 3Attorney Docket No. 701586-000154WOPTfor all other groups. FIG. 3H: FTIR and first derivative of FTIR of HEC, HECMTP and HECso films in -OH region showing increase in intermolecular H-bonds. First derivative was smoothed (Oth order, 200 neighbors) and inverted.

[0020] FIGs 4A-4E: HECMTP coatings are resistant to delamination and demonstrate softening on oxidation. FIG. 4A: Graph showing representative trace for lap shear test of HEC, HECMTP, and CEP coatings on glass. Inset: Detailed trace from 0.0 to 1.0 shear strain showing the CEP coating failure. FIG. 4B: Bar graph showing the ultimate shear stress (USS) for HEC, HECMTP, and CEP coatings on glass. *P<0.05, **P< 0.009, and not significant (ns), one-way ANOVA with Tukey's multiple comparison test. Graph shows mean±s.e.m. with individual data points showing n = 4 for HEC, and n = 3 per group. FIG.4C: Graph showing representative trace for tensile test of HECMTP films incubated for 7d in PBS, 7d in PBS + 80pM H2O2, or 4d in PBS + 800pM H2O2. FIG. 4D: Bar graph showing the elastic modulus for HECMTP films, incubated for 7d in PBS, 7d in PBS + 80pM H2O2, or 4d in PBS + 800pM H2O2. **P<0.002, ***P< 0.0004, and not significant (ns), one-way ANOVA with Tukey's multiple comparison test. Graph shows mean ± s.e.m. with individual data points showing n = 4 per group. FIG. 4E: Bar graph showing elastic modulus of HECMTP coatings incubated in PBS for Id, then measured by atomic force microscopy (AFM) before and after incubation in PBS + 80pM H2O2 for 7d. ***P< 0.0001, Student’s t-test (paired). Graph shows mean ± s.e.m. with individual data points showing n = 6.

[0021] FIGs. 5A-5G: HECMTP minimally scatters visible and fluorescent light, enabling optical applications. FIG.5A: Representative brightfield images of printed Glia Engineering logo covered by a glass coverslip with no coating, HECMTP, HECMTP + 1.28mM H2O2 for Id, or opaque tape. FIG. 5B: Graph showing the sharpness %change relative to ground truth (the logo without the coverslip). Not significant (ns) and ***P <0.0001 compared to glass or as designated, one-way ANOVA with Tukey's multiple comparison test. Graph shows mean ± s.e.m. with individual data points showing n = 3 for all groups. FIG. 5C: Graph showing UV-Vis trace from 300-900nm for glass coverslips that are: uncoated, or have black ink, tape, HECMTP or HECMTP + 1.28mM H2O2 for Id coatings applied. Each trace shows mean ± s.e.m., with s.e.m. represented as light shaded areas. FIG. 5D: Widefield fluorescence images showing DAPI-stained, coronal, murine brain sections with and without a HECMTP coating on the glass coverslip, or with a Gaussian Blur filter.FIG. 5E: Bar graph showing the sharpness scores for images of murine brain sections with uncoated or HECMTP coated glass coverslips. Not significant (ns), Student’s t-test. Graph shows mean ± s.e.m. with individual data points showing n = 12 images per group. Line plot showing the sharpness scores of images of brain sections with uncoated glass coverslips with Gaussian filters of increasing size applied. Trace shows mean ± s.e.m., with s.e.m. represented as light shaded areas, and n = 12 images per group. FIG. 5F: 2-photon fluorescent images of sub-resolution fluorescentAttorney Docket No. 701586-000154WOPTbeads, covered with a glass coverslip or a glass coverslip with a press fit film of either HECMTP or HECMTP + 80pM H2O2 for 7d. Overlaid traces are one-dimensional Gaussian fits characterizing the bead point spread function (PSF). FIG. 5G: Graph showing the average apparent size of subresolution fluorescent beads as a function of film thickness for an uncoated glass coverslip or a glass coverslip with a press fit film of either HECMTP or HECMTP + 80pM H2O2 for 7d. Apparent size was measured by the full width at half maximum (FWHM) of a ID Gaussian fit. Graph shows mean ± s.e.m. with n = 3 beads per group. Line shows linear regression of all data points, and the correlation is reported as Pearson’s Correlation Coefficient (r).

[0022] FIGs. 6A-6H: HECMTP coatings demonstrate controlled drug release. FIG. 6A:Graph showing 28d release profile for Coumarin 6 (C6), 7-Diethylamino-4-methylcoumarin (Cl), and 4-methylumbelliferone (4MU). Molecules were released into PBS (d0-dl4) or PBS + 0.1% Triton X-100 (dl5-d28). FIG. 6B: Graph showing 28d release profile for FITC-dextran polymers (lOkDa, 70kDa, and 150kDa). Polymers were released into PBS (d0-dl4), PBS + 80pMH2O2 (dl 5-d21), or PBS + 320pM H2O2 (d22-d28). FIG. 6C: Graph showing the average daily dextran for release from d8-dl4, dl5-d21, and d22-d28. All statistical comparisons are made with the previous duration (i.e. DIO d22-d28 is compared with dl5-d21) *P<0.05, ***P< 0.0007, and not significant (ns), two-way ANOVA with Tukey's multiple comparison test. Graph shows mean ± s.e.m. with individual data points showing n = 3 per group. FIG. 6D: Graph showing 20d release profile for 70kDa FITC-Dextran (D70) from HECMTP films into PBS, PBS + 80pM H2O2, or PBS + 800pM H2O2. *P<0.02, **P<0.003, ***P<0.0001 compared to PBS. Two-way ANOVA with Tukey's multiple comparison test for all 3 groups (800pM H2O2 comparisons). Two-way ANOVA with Sidak multiple comparison test between 80pM H2O2 and PBS groups (80pM H2O2 comparisons). Graph shows mean ± s.e.m. with individual data points showing n = 3 per group. FIG.6E: Graph showing the average daily D70 release from d6-dl0, dl 1 -dl 5, and dl6-d20. *P<0.03, **P<0.008, ***p<0.0002 as designated, two-way ANOVA with Tukey's multiple comparison test. Graph shows mean ± s.e.m. with individual data points showing n = 3 per group. FIG. 6F: Graph showing 12d daily D70 release profile into PBS with pulses of PBS + 800pM H2O2 at 2d intervals. FIG. 6G:Graph showing 12d daily D70 release profile into PBS with pulses of PBS + 80pM / 320pM H2O2 at 2d intervals. FIG. 6H: Graph showing relationship between D70 release and H2O2 pulse concentration. Data was corrected for baseline release using PBS daily release values and line of best fit was fit with a simple linear regression.

[0023] FIGs 7A-7I: HECMTP materials are non-fouling in vitro and in vivo. FIG. 7A:Cytotoxicity assay using Calcein AM demonstrates that coatings of HEC, HECMTP, and HECMTP treated with 320pM H2O2 are cytocompatible. Not significant (ns) and **P <0.008 compared to HEC, one-way ANOVA with Tukey's multiple comparison test. FIG. 7B: Oxidation of HECMTPAttorney Docket No. 701586-000154WOPTwith all concentrations of H2O2 leads to a significant decrease in astrocyte fouling relative to an untreated polystyrene (PS) surface. ***P <0.0001, one-way ANOVA with Tukey's multiple comparison test. FIG. 7C: Phase contrast images showing morphology of cells seeded on an untreated polystyrene (PS) surface, HECMTP, and HECMTP treated with either 320 or 20pM H2O2.FIG. 7D: Survey and detail images of histology sections stained with Masson’s Trichrome (MT) showing implant site and foreign body response (FBR) to subcutaneously implanted HECMTP, HECHEX, HECOCT, and regenerated cellulose (RC) films after 28d. Materials are marked with * and the panniculus camosus with PC. FIG. 7E: Detail images of histology sections stained with hematoxylin and eosin (H& E) showing FBR to subcutaneously implanted HECMTP, HECHEX, and HECOCT films after 28d. Materials are marked with *. FIG. 7F: Brightfield images of hydrated HECMTP films before and after 4wk subcutaneous (subq) implantation. FIG.7G: Quantification of remodeled tissue thickness for HECMTP, HECHEX, HECOCT, and RC films. Not significant (ns) and ***p <0.0003, one-way ANOVA with Tukey's multiple comparison test. Graph shows mean ± s.e.m. with individual data points showing n = 3 for HECOCT, n = 4 for HECHEX, and n = 5 for HECMTP and RC. FIG.7H: Quantification of deep capsule thickness for HECMTP and RC films. Graph shows mean ± s.e.m. with individual data points showing n = 5 per group. FIG. 71: FTIR of HECMTP films pre- and post-implantation. Dashed boxes highlight regions of interest from 1500-1750 cm’1and 3000-3750 cm’1. First derivative was smoothed (Oth order, 100 neighbors) and inverted.

[0024] FIGs. 8A-8D: Differences in HECMTP functionality yields either a gel-like or an insoluble material in PBS. FIG. 8A: HEC structure and size exclusion chromatography (SEC) trace with resulting molecular weight (Mw) and dispersity (D). FIG. 8B: HEC and HECMTP at 9, 16, and 21mol% functionality were solubilized at 5wt% in PBS and allowed to equilibrate for a week. Images are taken of the dry polymer (dry), after the addition of PBS (dO), and after 1 week of equilibration at room temperature (d7). FIG. 8C: 'H NMR of HEC and HECMTP at 9, 16, and 21mol% functionality in dDMSO with integration of MTP-associated peaks. FIG. 8D: FTIR of HEC and HECMTP at 9, 16, and 21mol% functionality highlighting MTP-associated peaks.

[0025] FIGs. 9A-9C: NMR characterization of HEC, HECMTP, and HECso. FIG. 9A:1H NMR of HEC in dTFA with integration. FIG. 9B: 'H NMR of HECMTP in dTFA with integration normalized to conserved HEC peaks and highlighting MTP-associated peaks. FIG. 9C: 'H NMR of HECso in dTFA with integration normalized to conserved HEC peaks and highlighting SO-associated peaks.

[0026] FIGs. 10A-10C: FTIR and NMR characterization of HEC, HECMTP, and HECso reveals maintenance of MTP functionality after oxidation. FIG. 10A: FTIR with characteristic absorption bands of chemical bonds in HEC, HECMTP and HECso. Spectra is normalized so thatAttorney Docket No. 701586-000154WOPTthe total area under the curve (AUC) for each condition is 1000. Highlights demonstrate MTP and SO -associated peaks. FIG. 10B: Detailed image showing FTIR spectra region from 1200- 1900cm'1with green integration showing the AUC for the thiocarbamoyl stretches, normalized such that the total AUC for both thiocarbamoyl stretches for HECMTP add to 100%. FIG. 10C: 'H NMR of HECMTP, HECSO, and HECMTP treated with either 80pM or 320pM H2O2 in dTFA highlighting MTP-associated and SO-associated peaks.

[0027] FIG. 11: XPS characterization of HEC, HECMTP and oxidized HECMTP. Survey scan of HEC, HECMTP and oxidized HECMTP (80pM H2O2 for 7d and 800pM H2O2 for Id) shows the presence of MTP-related peaks (Nls, S2s, S2p) in HECMTP and oxidized HECMTP materials and absence of these peaks in HEC. Inset plot shows a high-resolution scan of the characteristic sulfur 2p (S2p) peak.

[0028] FIG. 12: FTIR of HEC, HECMTP and oxidized HECMTP films shows minimal changes to thiocarbamoyl stretches. FTIR of HEC, HECMTP and oxidized HECMTP films (80pM H2O2 for 7d, 1% H2O2 and 800pMH202 for Id). Gray highlight shows -O-CO- stretch, associated with increased oxidation, which only begins to emerge at supraphysiological H2O2 concentrations.

[0029] FIGs. 13A-13C: FTIR characterization of HEC and HEC treated with 1% H2O2 for 24hrs. FIG. 13A: Full FTIR with highlights show key HEC-related peaks. FIG. 13B: Magnified plot from 1200-2000 cm'1demonstrating no detectable emergence of carbonyl stretch (aldehyde) that would suggest oxidation of the cellulose backbone or ethylene oxide side chains. FIG. 13C:Magnified plot from 2500-3800 cm'1demonstrating no detectable change in hydroxyl stretch.

[0030] FIGs. 14A-14C: DSC / TGA characterization of HEC and HECMTP. FIG. 14A:Differential scanning calorimetry (DSC) plots for HEC and HECMTP taken from 30°C to 400°C.FIG. 14B: Thermogravimetric analysis (TGA) of HEC and HECMTP between 30°C and 400°C demonstrating that HEC and HECMTP are thermally stable up to 215°C after which HECMTP loses approximately 20% of its total mass. FIG. 14C: dTGA plot derived from TGA for HEC and HECMTP-

[0031] FIGs. 15A-15D: HECMTP solution viscosity is temperature dependent and solution viscosity dictates coating thickness. FIG. 15A: Dynamic rheological shear rate sweep measurements for HECMTP solubilized at 5wt% in a 100 / 0 DMSO solvent system showing viscosity (Pa.s) against increasing temperature (°C). FIG. 15B: Box-and- whisker plot showing the decrease in measured viscosity (Pa.s) at fixed temperature values. **P<0.01 and ***P <0.0001 compared to 30°C or as designated. FIG. 15C: Bar graph showing effect of solvent system on coating thickness at a fixed concentration of 5wt%. Not significant (ns) compared to 100 / 0 DMSO / Acetone or as designated. FIG. 15D: Bar graph showing effect of concentration on coating thickness in a fixed solvent system (100 / 0 DMSO / Acetone). **P < 0.005, not significant (ns) compared to lwt%Attorney Docket No. 701586-000154WOPTor as designated. All statistical tests were one-way ANOVAs with Tukey's multiple comparison tests. Graphs show mean ± s.e.m. with individual data points showing n = 3 per group.

[0032] FIGs. 16A-16H: Solvent system, concentration, and number of dips can affect coating surface roughness. Profilometry data showing the measured surface roughness across 1 mm of coating for different solvent systems. FIG. 16A: (DMSO / Acetone) at 5wt% FIG. 16B: concentrations in 100 / 0 DMSO / Acetone and FIG. 16C: number of dips in 100 / 0 DMSO / Acetone at 5wt%. Roughness trace has been baseline corrected and the average displacement set as 0 nm. Gray dashed line shows the roughness of the glass without a coating. FIG. 16D: Bar graph showing the effect of solvent system on the average roughness of the coating. *P <0.03, not significant (ns) compared to 100 / 0 DMSO / Acetone or as designated. FIG. 16E: Bar graph showing the effect of concentration on the average roughness of the coating. **P< 0.01, not significant (ns) compared to lwt% or as designated. FIG. 16F: Bar graph showing the effect of multiple dips on the average roughness of the coating. *P<0.04, not significant (ns) compared to 1 dip or as designated. All statistical tests were one-way ANOVAs with Tukey's multiple comparison tests. Graphs show mean ± s.e.m. with individual data points showing n = 3 per group. FIG. 16G: Scanning electron microscopy (SEM) micrograph of HECMTP coated on an aluminum SEM stub at 3wt% imaged with 4-segmented backscattered electron (BSE) detector. Micrographs show regions of interest (ROI) imaged with three detector modes: Full, Topo A (x-bias), and Topo B (y-bias). FIG. 16H: SEM of HECMTP coated on an aluminum SEM stub at lwt% (3 layers) and 3wt% (1 layer). Micrographs were imaged on Full detector mode and arrows highlight small surface features on lwt% HECMTP coating.

[0033] FIGs. 17A-17G: HECHEX and HECOCT characterization. FIG. 17A: Synthesis scheme for base-catalyzed, nucleophilic addition of HEX-ITC to HEC to prepare HECHEX. FIG.17B: Synthesis scheme for base-catalyzed, nucleophilic addition of OCT-IC to HEC to prepare HECOCT. FIG. 17C:1H NMR of HEC, HECMTP, HECHEX, and HECOCT in dDMSO. FIG. 17D:FTIR characterization HEC, HECMTP, HECHEX, and HECOCT, highlights demonstrate MTP, HEX, and OCT -associated peaks. FIG. 17E: Contact angle data for HEC, HECMTP, HECHEX, and HECOCT. Not significant (ns), **P< 0.004, and ***P< 0.0008 compared to HECMTP or as designated, one-way ANOVA with Tukey's multiple comparison test. Graph shows mean ± s.e.m. with individual data points showing n = 6 for HECMTP and n = 4 for all other groups. FIG. 17F:Change in wet mass of HECMTP, HECHEX, and HECOCT coatings over 7d. Not significant (ns), *P < 0.04, **P < 0.0015, and ***P < 0.0001 compared to HECMTP, two-way ANOVA with Tukey's multiple comparison test. Graph shows mean ± s.e.m. with individual data points showing n = 3 for HECMTP and n = 4 for all other groups. FIG. 17G: %Change in dry mass of HEC, HECMTP, HECHEX, and HECOCT coatings after 7d. Not significant (ns), and ***P < 0.0001 compared to HECAttorney Docket No. 701586-000154WOPTor as designated, one-way ANOVA with Tukey's multiple comparison test. Graph shows mean ± s.e.m. with individual data points showing n = 3 for HEC and HECMTP and n = 4 for all other groups.

[0034] FIGs. 18A-18C: Detailed NMR characterization of HECHEX and HECOCT. FIG.18A:1H NMR of HEC in dDMSO. FIG. 18B:1H NMR of HECHEX in dDMSO with integration normalized to conserved HEC peaks and highlighting HEX-associated peaks. FIG. 18C:1H NMR of HECOCT in dDMSO with integration normalized to conserved HEC peaks and highlighting OCT-associated peaks.

[0035] FIG. 19: HECOCT DMSO solubility limits coating applications. Brightfield images show HECOCT with 8 mol%, 12 mol%, and 18 mol% functionality and HECMTP at 21 mol% functionality solubilized at 3wt% in DMSO. 12 mol% and 18 mol% HECOCT readily goes into solution at 50°C but quickly crystallizes out on returning to room temperature, while 8 mol% remains stable. Meanwhile, HECMTP is stable in solution at functionalities as high as 21 mol% at a concentration of 3wt% in DMSO.

[0036] FIG. 20: HECOCT is not readily soluble in common organic solvents. 18mol% HECOCT was solubilized at 3wt% in water, acetone, toluene, and 50 / 50 DMSO / toluene. This material forms a hydrogel in water, is insoluble in acetone and toluene, and is partially soluble in 50 / 50 DMSO / toluene as evidenced by the viscous / gel-like patterning seen above.

[0037] FIGs.21A-21D: Oxidation of HEC, HECMTP, HECHEX, and HECOCT with 1% H2O2demonstrates no significant loss of MTP, HEX, or OCT functional groups. FTIR comparing (A) HEC (FIG.21A) HECMTP (FIG.21B) HECHEX (FIG.21C) and HECOCT (FIG.21D) both untreated and treated with 1% H2O2for 24hrs. Highlights show either -CS-NH- and -O-CS- (thiocarbamoyl) or -CO-NH- and -O-CO- (carbamate) stretches.

[0038] FIGs. 22A-22C: H2O2scavenging displays second order kinetics. FIG. 22A:Graph of H2O2scavenging kinetics replotted such that the y-axis is 1 / concentration. This shows that the reaction demonstrates 2ndorder kinetics, k = 0.00059. FIG. 22B: %H2O2remaining after 1 d of H2O2reacting with HECMTP coating. Red and blue highlights show the varied or fixed variable in the reaction rate equation. ***P< 0.0001, Student’s t-test. Graph shows mean ± s.e.m. with individual data points showing n = 4 per group. FIG.22C: H2O2scavenged (pmol / cm2) by HECMTP coating exposed to varied concentration of H2O2on dl and then a fixed concentration of H2O2(4mM) on d2. Concentration of MTP moieties is fixed on dl, but following exposure to varied concentration of H2O2on dl, there is a varied molar quantity of unreacted MTP moieties between conditions, creating a varied MTP concentration on d2. Dashed lines indicate the slope of the line between dl and d2. Red and blue highlights show the varied or fixed variable in the reaction rateAttorney Docket No. 701586-000154WOPTequation across dl and d2. Slopes were compared using a two-way ANOVA with Tukey's multiple comparison test. Graph shows mean ± s.e.m. with individual data points showing n = 4 per group.

[0039] FIG. 23: Oxidized HECMTP coatings exhibit increased swelling. Change in wet mass of HECMTP coatings over 7d exposed to either PBS or PBS + 80μM H₂O₂. **P= 0.0016 comparisons between HECMTP and HECMTP + 80μM H₂O₂ at equivalent timepoints, two-way ANOVA with Tukey's multiple comparison test. Graph shows mean ± s.e.m., n = 3 per group.

[0040] FIGs. 24A-24B: HECMTP films exhibit strong hydrogen bonding. FIG. 24A:Brightfield images showing a dry HECMTP film that swells significantly in DMSO over 48 hrs, but completely dissolves in HFIP (a solvent that is excellent at disrupting hydrogen bonding). FIG.24B: %Mass change of HECMTP films swollen in DMSO relative to HECMTP films that were dissolved in HFIP. ***P=0.0002, Student’s t-test. Graph shows mean ± s.e.m., n = 3 per group.

[0041] FIGs.25A-25E: Coating delamination testing set-up and results. FIG.25A: Image and diagram demonstrating the assembly of lap shear slides. FIG. 25B: Comparison of HEC, HECMTP, and crosslinked ethoxylated polyol (CEP) shear modulus. ***P<0.001, not significant (ns) compared to HEC or as designated, one-way ANOVA with Tukey's multiple comparison test. Graph shows mean ± s.e.m. with individual data points showing n = 4 for HEC and n = 3 for all others. FIG.25C: Comparison of HEC, HECMTP, and CEP shear strain at the ultimate shear stress (USS). Not significant (ns) compared to HEC or as designated, one-way ANOVA with Tukey's multiple comparison test. Graph shows mean ± s.e.m. with individual data points showing n = 4 for HEC and n = 3 for all others. FIG. 25D: Comparison of HEC, HECMTP, and CEP toughness as determined by taking the area under the curve (AUC) of the shear stress-shear strain curve. Not significant (ns) compared to HEC or as designated, one-way ANOVA with Tukey's multiple comparison test. Graph shows mean ± s.e.m. with individual data points showing n = 4 for HEC and n = 3 for all others. FIG. 25E: Comparison of HEC, HECMTP, and CEP failure mechanisms demonstrating that HEC-based materials fail by both adhesive and cohesive failure, while CEP demonstrates pure adhesive failure.

[0042] FIGs. 26A-26D: Bulk material properties by tensile testing. FIG. 26A: Graph showing representative trace of tensile testing for dry HECMTP films and hydrated (7d in PBS) regenerated cellulose (RC). FIG.26D: Bar graph showing the elastic moduli of dry HECMTP films and hydrated (7d in PBS) RC. **P<0.007, Student’s t-test. Graph shows mean ± s.e.m. with individual data points showing n = 4. FIG. 26C: Bar graph showing the strain at failure for films of dry HECMTP, hydrated HECMTP (7d in PBS), HECMTP hydrated 7d in PBS + 80pM H2O2, HECMTP hydrated 4d in PBS + 800pM H2O2, and hydrated RC (7d in PBS). *P<0.03, **P<0.0049, and not significant (ns) compared to dry HECMTP or as designated, one-way ANOVA with Tukey's multiple comparison test. Graph shows mean ± s.e.m. with individual data points showing n = 4. FIG.26D:Attorney Docket No. 701586-000154WOPTBar graph showing the ultimate tensile strength (UTS) of films of dry HECMTP, hydrated HECMTP (7d in PBS), HECMTP hydrated 7d in PBS + 80pM H2O2, HECMTP hydrated 4d in PBS + 800pM H2O2, and hydrated RC (7d in PBS). ***P<0.0001 and not significant (ns) compared to dry HECMTP or as designated, one-way ANOVA with Tukey's multiple comparison test. Graph shows mean ± s.e.m. with individual data points showing n = 4.

[0043] FIGs. 27A-27D: HECMTP coatings exhibit minimal fluorescent scattering. FIG.27A: Representative widefield fluorescence images of stained mouse brain sections under HECMTP-coated and uncoated coverslips. FIG. 27B: Graph showing the change in sharpness score in the HECMTP-coated vs uncoated images. Not significant (ns) and ***P <0.0001 compared to 0, one sample t-test. Graph shows mean ± s.d. with individual data points showing the difference between n = 12 coated ROIs and the mean of n = 12 uncoated ROIs for all groups. FIG. 27C: Images showing a characteristic ROI from a DAPI-stained mouse brain section under an uncoated coverslip after application of Gaussian blurring filters of increasing size. FIG. 27D: Graph showing the average apparent size of sub-resolution fluorescent beads for an uncoated glass coverslip or a glass coverslip with a press fit film of either HECMTP or HECMTP + 80pM H2O2 for 7d. Data is binned by film thickness ranging from 25-50pm or 125-150pm. Apparent bead size was measured by the full width at half maximum (FWHM) of a 1D Gaussian fit. Not significant (ns), **P< 0.01, and ***p< 0.0002, compared to glass or as designated, two-way ANOVA with Tukey's multiple comparison test. Bar graph shows mean ± s.e.m. with individual data points showing n = 3 for all groups.

[0044] FIG. 28: HECMTP film daily release of D70. Graph showing 20d daily release for 70kDa FITC-Dextran (D70) from HECMTP films into PBS, PBS + 80pM H2O2, or PBS + 800pM H2O2. All statistical comparisons are made relative to the PBS control at a given time point (ie. PBS vs PBS + 80pM H2O2 at day 5) and color-coded for clarity. *P<0.04, **P<0.007, ***p<0.0001, two-way ANOVA with Tukey's multiple comparison test. Graph shows mean ± s.e.m. with individual data points showing n = 3 per group.

[0045] FIGs. 29A-29C: HECMTP coatings exhibit minimal protein adhesion. FIG. 29A:Plot showing the relative fluorescent intensity of albumin-fluorescein isothiocyanate conjugate (FITC-BSA) adsorbed to gelatin, HECMTP, and HECMTP + 800pM H2O2 (Id) materials. Not significant (ns) and ***P< 0.0001 compared to gelatin or as designated, one-way ANOVA with Tukey's multiple comparison test. Bar graph shows mean ± s.e.m. with individual data points showing n = 8 for all groups. FIG. 29B: Overview of gelatin, HECMTP, and HECMTP + 800pM H2O2 (Id) materials with adsorbed FITC-BSA. Dashed box indicates representative ROI from which intensity measurements were taken. FIG.29C: Detail images showing the specified ROI in (FIG. 29B)Attorney Docket No. 701586-000154WOPT

[0046] FIGs. 30A-30B: HECMTP coatings can be readily sterilized with minimal changes in mass loss and material properties. FIG. 30A: UV-Vis spectra of HECMTP coatings on glass coverslips with no treatment, IPA sterilization with a single dip, as well as soaking overnight, and autoclaved. Spectra are background subtracted from a blank glass coverslip spectra. Graphs show mean ± s.e.m., with s.e.m. represented as light shaded areas. FIG. 30B: %Mass loss for HECMTP coatings with IPA sterilization with a single dip, as well as soaking overnight, and autoclaved. Not significant (ns) and *P<0.03 compared to 70% IPA dip or as designated, one-way ANOVA with Tukey's multiple comparison test. Graph shows mean ± s.e.m. with individual data points showing n = 3 for all groups.

[0047] FIGs. 31A-31B: Characterization of swelling and dissolution of implanted biomaterials. FIG. 31A: Change in wet mass of HECMTP, HECHEX, and HECOCT and RC after Id in PBS. Not significant (ns), and ***P< 0.0006 compared to HECMTP or as designated, one-way ANOVA with Tukey's multiple comparison test. Graph shows mean ± s.e.m. with individual data points showing n = 3 for HECMTP and n = 4 for all other groups. FIG. 31B: %Dry mass loss of HECMTP, HECHEX, HECOCT, and RC after 7d in PBS. Not significant (ns), and ***P< 0.0001 compared to HECMTP or as designated, one-way ANOVA with Tukey's multiple comparison test. Graph shows mean ± s.e.m. with individual data points showing n = 3 for HECMTP and n = 4 for all other groups.

[0048] FIG. 32: Images of cellulose-based biomaterial explants after 4 weeks of subcutaneous implantation. Arrows and dashed outlines indicate either the implanted material (HECMTP, RC) or the foreign body response to the implanted material (HECHEX, HECOCT).

[0049] FIG. 33: H& E staining of subcutaneous implant tissue. Survey and detail images of histology sections stained with hematoxylin and eosin (H& E) showing implant site and foreign body response (FBR) to subcutaneously implanted HECMTP, HECHEX, HECOCT, and regenerated cellulose (RC) films after 28d.

[0050] FIGs. 34A-34C: Histological analysis of subcutaneous implant tissue reveals no significant difference in HECMTP and RC FBR. Plots comparing macrophage density (FIG. 34A) fibroblast density (FIG. 34B) and dense collagen thickness (FIG.34C) between HECMTP and RC materials. Not significant (ns), Student’s t-test. Graphs show mean ± s.e.m. with n = 5 per group.DETAILED DESCRIPTION

[0051] In one aspect, provided herein is a thioether-functionalized cellulose polymer. Generally, the thioether-functionalized cellulose polymer comprises a cellulose backbone of repeating anhydroglucose units and thioether substituents covalently attached to at least a portion of the hydroxyl groups of said repeating anhydroglucose units.Attorney Docket No. 701586-000154WOPT

[0052] As used herein, the term “anhydroglucose unit” refers to a glucose monomer in (co)polymerized form or as part of a polysaccharide. The anhydroglucose unit may contain from 1 to 3 hydroxyl groups.

[0053] As used herein, the term "thioether" refers to the group -S-, i.e., bonded to a sulfur atom of two other groups, typically in which the sulfur atom is bonded to two carbon atoms.

[0054] As used herein, a “thioether substituent” or “thioether group” refers to thioethers of the formula L — S — Rs, where Lis a linker connecting the sulfur atom to an anhydroglucose unit (e.g., to a hydroxyl of the anhydroglucose unit) in the cellulose backbone, and Rsis H, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl or heteroaryl, each of which can be optionally substituted with 1, 2, 3, 4, 5 or more independently selected substituents. In some embodiments of any one of the aspects, Rsis an optionally substituted alkyl group. For example, Rsis an optionally substituted Ci-Cealkyl group. In some embodiments of any one of the aspects, Rsis methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, t-butyl, n-pentyl or n-hexyl, each of which can be optionally substituted with 1, 2, 3, 4 or more independently selected substituents. In some preferred embodiments, Rsis methyl.

[0055] The term “linker” means an organic moiety that connects two parts of a compound. Linkers typically comprise a direct bond or an atom such as oxygen or sulfur, a unit such as NR1, C(O), C(O)O, C(O)NR1, SO, SO2, SO2NH or a chain of atoms, such as substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, arylalkyl, arylalkenyl, arylalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkylarylalkyl, alkylarylalkenyl, alkylarylalkynyl, alkenylarylalkyl, alkenylarylalkenyl, alkenylarylalkynyl, alkynylarylalkyl, alkynylarylalkenyl, alkynylarylalkynyl, alkylheteroarylalkyl, alkylheteroarylalkenyl, alkylheteroarylalkynyl, alkenylheteroarylalkyl, alkenylheteroarylalkenyl, alkenylheteroarylalkynyl, alkynylheteroarylalkyl, alkynylheteroarylalkenyl alkynylheteroarylalkynyl, alkylheterocyclylalkyl, alkylheterocyclylalkenyl alkylhererocyclylalkynyl, alkenylheterocyclylalkyl, alkenylheterocyclylalkenyl alkenylheterocyclylalkynyl, alkynylheterocyclylalkyl, alkynylheterocyclylalkenyl alkynylheterocyclylalkynyl, alkylaryl, alkenylaryl, alkynylaryl, alkylheteroaryl, alkenylheteroaryl, alkynylhereroaryl, where one or more methylenes can be interrupted or terminated by O, S, S(O), SO2, N(R')2, C(O), cleavable linking group, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclic; where R1is hydrogen, acyl, aliphatic or substituted aliphatic. In some embodiments, linker L is -C(O)NH-L1-, where L1is a substituted or unsubstituted alkylene, substituted or unsubstituted alkenylene, substituted orAttorney Docket No. 701586-000154WOPTunsubstituted alkynylene. For example, L1is a Ci-Cealkylene. In some embodiments, L1is methylene, ethylene, propylene, butylene, pentylene, or hexylene.

[0056] As used herein, “covalently attached”, “covalently linked” and “covalently bonded” all refer to chemical moieties that are bound via a covalent bond.

[0057] As used herein, “hydroxyl group” refers to an -OH moiety.

[0058] As used herein, the term “polymer” refers to a molecule having two or more units derived from the same monomer component. Thus, the term “polymer” is intended to include homopolymers, copolymers, interpolymers, terpolymers, multi-component polymers, graft-copolymers, block-co-polymers, and the like.

[0059] In some embodiments of any of the aspects, the polymer is hydroxyethyl cellulose (HEC) or methyl cellulose (MC) or hydroxy propyl methylcellulose (HPMC). For example, the polymer is hydroxyethyl cellulose.

[0060] As used herein, “hydroxyethyl cellulose” or “HEC” is a cellulose derivative wherein at least a portion of the hydrogens from the hydroxyl groups of the glucose monomers are replaced with hydroxyethyl (-CH2CH2OH) groups.

[0061] As used herein, “methyl cellulose” or “MC” is a cellulose derivative wherein at least a portion of the hydrogens from the hydroxyl groups of the glucose monomers are replaced with methyl (-CH3) groups.

[0062] As used herein, “hydroxy propyl methylcellulose” or “HPMC”, also known as “hypromellose”, is a cellulose derivative wherein at least a portion of the hydrogens from the hydroxyl groups of the glucose monomers are replaced with -CH₃ groups and -CH2CH(OH)CH3 groups.

[0063] In some embodiments of any of the aspects, the polymer is oxidation-responsive.

[0064] As used herein, “oxidation responsive” refers to a molecule, e.g., a polymer that undergoes a chemical or physical change when exposed to oxidative conditions, such as reactive oxygen species, peroxides, or molecular oxygen.. Potential responses include, but are not limited to, bond cleavage, crosslinking or degradation of polymer backbone, cleavage of polymer backbone, releasing a payload, and / or change in hydrophilicity, solubility, color, and / or fluorescence.

[0065] In some embodiments of any of the aspects, the polymer undergoes a hydrophobic-to-hydrophilic transition upon exposure to a reactive oxygen species (ROS).

[0066] As used herein, the term “hydrophobic-to-hydrophilic transition” refers to a change in a material’s or molecule’s surface or bulk properties in which it goes from repelling water (hydrophobic) to attracting or interacting favorably with water (hydrophilic).Attorney Docket No. 701586-000154WOPT

[0067] As used herein, “reactive oxygen species” or “ROS” refers to a group of unstable oxygen containing molecules. ROS are commonly produced by gaseous oxygen (O2), water, and hydrogen peroxide (H2O2). Some prominent ROS are hydroperoxides (ROOH), superoxides, hydroxyl radicals, and singlet oxygen.

[0068] In some embodiments of any of the aspects, at least a portion of the thioether substituents of the polymer are oxidized, e.g. to sulfoxide or sulfone.

[0069] As used herein, “sulfoxide” refers a molecule comprising a sulfinyl (S=O) functional group bound to two carbon atoms (e.g., R(SO)R). As used herein, “sulfone” refers to a molecule comprising a sulfur atom which is doubly bonded to two oxygen atoms and singly bonded to two carbon atoms (e.g., R(SO2)R).

[0070] In some embodiments of any of the aspects, at least a portion of the thioether substituents of the polymer are alkylated to sulfonium ions.

[0071] As used herein, “alkylated” refers to a molecule which has undergone a chemical process to add an alkyl group to it.

[0072] As used herein, “Sulfonium ion” refers to a molecule comprising a sulfur atom bonded to three organic groups (e.g., [SRs]+).

[0073] In some embodiments of any of the aspects, at least a portion of the thioether substituents of the polymer are zwitterionic.

[0074] As used herein, “zwitteronic” refers to a molecule which comprises both a positive charge and a negative charge.

[0075] In some embodiments of any of the aspects, at least 2.5 mol % of the hydroxyl groups in the polymer are modified with the thioether substituent. For example, about 2.5 to about 95 mol% of the hydroxyl groups in the polymer are modified with the thioether substituent. In some embodiments of any one of the aspects, the amount of hydroxyl groups in the polymer that are modified with the thioester substituent is about 2.5 mol%, about 5.0 mol%, about 7.5 mol%, about 10.0 mol%, about 12.5 mol%, about 15.0 mol%, about 17.5 mol%, about 20.0 mol%, about 22.5 mol%, about 25.0 mol%, about 27.5 mol%, about 30.0 mol%, about 32.5 mol%, about 35.0 mol%, about 37.5 mol%, about 40.0 mol%, about 42.5 mol%, about 45.0 mol%, about 47.5 mol%, about 50.0 mol%, about 52.5 mol%, about 55.0 mol%, about 57.5 mol%, about 60.0 mol%, about 62.5 mol%, about 65.0 mol%, about 67.5 mol%, about 70.0 mol%, about 72.5 mol%, about 75.0 mol%, about 77.5 mol%, about 80.0 mol%, about 82.5 mol%, about 85.0 mol%, about 87.5 mol%, about 90.0 mol%, about 92.5 mol%, or about 95.0 mol%.

[0076] In some embodiments of any of the aspects, 5-30 mol% of the hydroxyl groups in the polymer are modified with the thioether substituent. For example, the amount of hydroxyl groups in the polymer that are modified with the thioester substituent is about 5 mol%, about 5.25Attorney Docket No. 701586-000154WOPTmol%, about 5.5 mol%, about 5.75 mol%, about 6 mol%, about 6.25 mol%, about 6.5 mol%, about 6.75 mol%, about 7 mol%, about 7.25 mol%, about 7.5 mol%, about 7.75 mol%, about 8 mol%, about 8.25 mol%, about 8.5 mol%, about 8.75 mol%, about 9 mol%, about 9.25 mol%, about 9.5 mol%, about 9.75 mol%, about 10 mol%, about 10.25 mol%, about 10.5 mol%, about 10.75 mol%, about 11 mol%, about 11.25 mol%, about 11.5 mol%, about 11.75 mol%, about 12 mol%, about 12.25 mol%, about 12.5 mol%, about 12.75 mol%, about 13 mol%, about 13.25 mol%, about 13.5 mol%, about 13.75 mol%, about 14 mol%, about 14.25 mol%, about 14.5 mol%, about 14.75 mol%, about 15 mol%, about 15.25 mol%, about 15.5 mol%, about 15.75 mol%, about 16 mol%, about 16.25 mol%, about 16.5 mol%, about 16.75 mol%, about 17 mol%, about 17.25 mol%, about 17.5 mol%, about 17.75 mol%, about 18 mol%, about 18.25 mol%, about 18.5 mol%, about 18.75 mol%, about 19 mol%, about 19.25 mol%, about 19.5 mol%, about 19.75 mol%, about 20 mol%, about 20.25 mol%, about 20.5 mol%, about 20.75 mol%, about 21 mol%, about 21.25 mol%, about 21.5 mol%, about 21.75 mol%, about 22 mol%, about 22.25 mol%, about 22.5 mol%, about 22.75 mol%, about 23 mol%, about 23.25 mol%, about 23.5 mol%, about 23.75 mol%, about 24 mol%, about 24.25 mol%, about 24.5 mol%, about 24.75 mol%, about 25 mol%, about 25.25 mol%, about 25.5 mol%, about 25.75 mol%, about 26 mol%, about 26.25 mol%, about 26.5 mol%, about 26.75 mol%, about 27 mol%, about 27.25 mol%, about 27.5 mol%, about 27.75 mol%, about 28 mol%, about 28.25 mol%, about 28.5 mol%, about 28.75 mol%, about 29 mol%, about 29.25 mol%, about 29.5 mol%, about 29.75 mol%, or about 30 mol%.

[0077] In some embodiments of any of the aspects, the polymer comprises an average of about 0.5 to 2 thioether groups per anhydroglucose repeat unit. For example, the polymer comprises about 0.5 thioether groups per anhydroglucose repeat unit, about 0.51 thioether groups per anhydroglucose repeat unit, about 0.52 thioether groups per anhydroglucose repeat unit, about 0.53 thioether groups per anhydroglucose repeat unit, about 0.54 thioether groups per anhydroglucose repeat unit, about 0.55 thioether groups per anhydroglucose repeat unit, about 0.56 thioether groups per anhydroglucose repeat unit, about 0.57 thioether groups per anhydroglucose repeat unit, about 0.58 thioether groups per anhydroglucose repeat unit, about 0.59 thioether groups per anhydroglucose repeat unit, about 0.6 thioether groups per anhydroglucose repeat unit, about 0.61 thioether groups per anhydroglucose repeat unit, about 0.62 thioether groups per anhydroglucose repeat unit, about 0.63 thioether groups per anhydroglucose repeat unit, about 0.64 thioether groups per anhydroglucose repeat unit, about 0.65 thioether groups per anhydroglucose repeat unit, about 0.66 thioether groups per anhydroglucose repeat unit, about 0.67 thioether groups per anhydroglucose repeat unit, about 0.68 thioether groups per anhydroglucose repeat unit, about 0.69 thioether groups per anhydroglucose repeat unit, about 0.7 thioether groups per anhydroglucose repeat unit, about 0.71 thioether groups per anhydroglucose repeat unit, about 0.72 thioether groupsAttorney Docket No. 701586-000154WOPTper anhydroglucose repeat unit, about 0.73 thioether groups per anhydroglucose repeat unit, about 0.74 thioether groups per anhydroglucose repeat unit, about 0.75 thioether groups per anhydroglucose repeat unit, about 0.76 thioether groups per anhydroglucose repeat unit, about 0.77 thioether groups per anhydroglucose repeat unit, about 0.78 thioether groups per anhydroglucose repeat unit, about 0.79 thioether groups per anhydroglucose repeat unit, about 0.8 thioether groups per anhydroglucose repeat unit, about 0.81 thioether groups per anhydroglucose repeat unit, about 0.82 thioether groups per anhydroglucose repeat unit, about 0.83 thioether groups per anhydroglucose repeat unit, about 0.84 thioether groups per anhydroglucose repeat unit, about 0.85 thioether groups per anhydroglucose repeat unit, about 0.86 thioether groups per anhydroglucose repeat unit, about 0.87 thioether groups per anhydroglucose repeat unit, about 0.88 thioether groups per anhydroglucose repeat unit, about 0.89 thioether groups per anhydroglucose repeat unit, about 0.9 thioether groups per anhydroglucose repeat unit, about 0.91 thioether groups per anhydroglucose repeat unit, about 0.92 thioether groups per anhydroglucose repeat unit, about 0.93 thioether groups per anhydroglucose repeat unit, about 0.94 thioether groups per anhydroglucose repeat unit, about 0.95 thioether groups per anhydroglucose repeat unit, about 0.96 thioether groups per anhydroglucose repeat unit, about 0.97 thioether groups per anhydroglucose repeat unit, about 0.98 thioether groups per anhydroglucose repeat unit, about 0.99 thioether groups per anhydroglucose repeat unit, about 1 thioether groups per anhydroglucose repeat unit, about 1.01 thioether groups per anhydroglucose repeat unit, about 1.02 thioether groups per anhydroglucose repeat unit, about 1.03 thioether groups per anhydroglucose repeat unit, about 1.04 thioether groups per anhydroglucose repeat unit, about 1.05 thioether groups per anhydroglucose repeat unit, about 1.06 thioether groups per anhydroglucose repeat unit, about 1.07 thioether groups per anhydroglucose repeat unit, about 1.08 thioether groups per anhydroglucose repeat unit, about 1.09 thioether groups per anhydroglucose repeat unit, about 1.1 thioether groups per anhydroglucose repeat unit, about 1.11 thioether groups per anhydroglucose repeat unit, about 1.12 thioether groups per anhydroglucose repeat unit, about 1.13 thioether groups per anhydroglucose repeat unit, about 1.14 thioether groups per anhydroglucose repeat unit, about 1.15 thioether groups per anhydroglucose repeat unit, about 1.16 thioether groups per anhydroglucose repeat unit, about 1.17 thioether groups per anhydroglucose repeat unit, about 1.18 thioether groups per anhydroglucose repeat unit, about 1.19 thioether groups per anhydroglucose repeat unit, about 1.2 thioether groups per anhydroglucose repeat unit, about 1.21 thioether groups per anhydroglucose repeat unit, about 1.22 thioether groups per anhydroglucose repeat unit, about 1.23 thioether groups per anhydroglucose repeat unit, about 1.24 thioether groups per anhydroglucose repeat unit, about 1.25 thioether groups per anhydroglucose repeat unit, about 1.26 thioether groups per anhydroglucose repeat unit, about 1.27 thioether groups per anhydroglucose repeat unit, about 1.28 thioether groupsAttorney Docket No. 701586-000154WOPTper anhydroglucose repeat unit, about 1.29 thioether groups per anhydroglucose repeat unit, about 1.3 thioether groups per anhydroglucose repeat unit, about 1.31 thioether groups per anhydroglucose repeat unit, about 1.32 thioether groups per anhydroglucose repeat unit, about 1.33 thioether groups per anhydroglucose repeat unit, about 1.34 thioether groups per anhydroglucose repeat unit, about 1.35 thioether groups per anhydroglucose repeat unit, about 1.36 thioether groups per anhydroglucose repeat unit, about 1.37 thioether groups per anhydroglucose repeat unit, about 1.38 thioether groups per anhydroglucose repeat unit, about 1.39 thioether groups per anhydroglucose repeat unit, about 1.4 thioether groups per anhydroglucose repeat unit, about 1.41 thioether groups per anhydroglucose repeat unit, about 1.42 thioether groups per anhydroglucose repeat unit, about 1.43 thioether groups per anhydroglucose repeat unit, about 1.44 thioether groups per anhydroglucose repeat unit, about 1.45 thioether groups per anhydroglucose repeat unit, about 1.46 thioether groups per anhydroglucose repeat unit, about 1.47 thioether groups per anhydroglucose repeat unit, about 1.48 thioether groups per anhydroglucose repeat unit, about 1.49 thioether groups per anhydroglucose repeat unit, about 1.5 thioether groups per anhydroglucose repeat unit, about 1.51 thioether groups per anhydroglucose repeat unit, about 1.52 thioether groups per anhydroglucose repeat unit, about 1.53 thioether groups per anhydroglucose repeat unit, about 1.54 thioether groups per anhydroglucose repeat unit, about 1.55 thioether groups per anhydroglucose repeat unit, about 1.56 thioether groups per anhydroglucose repeat unit, about 1.57 thioether groups per anhydroglucose repeat unit, about 1.58 thioether groups per anhydroglucose repeat unit, about 1.59 thioether groups per anhydroglucose repeat unit, about 1.6 thioether groups per anhydroglucose repeat unit, about 1.61 thioether groups per anhydroglucose repeat unit, about 1.62 thioether groups per anhydroglucose repeat unit, about 1.63 thioether groups per anhydroglucose repeat unit, about 1.64 thioether groups per anhydroglucose repeat unit, about 1.65 thioether groups per anhydroglucose repeat unit, about 1.66 thioether groups per anhydroglucose repeat unit, about 1.67 thioether groups per anhydroglucose repeat unit, about 1.68 thioether groups per anhydroglucose repeat unit, about 1.69 thioether groups per anhydroglucose repeat unit, about 1.7 thioether groups per anhydroglucose repeat unit, about 1.71 thioether groups per anhydroglucose repeat unit, about 1.72 thioether groups per anhydroglucose repeat unit, about 1.73 thioether groups per anhydroglucose repeat unit, about 1.74 thioether groups per anhydroglucose repeat unit, about 1.75 thioether groups per anhydroglucose repeat unit, about 1.76 thioether groups per anhydroglucose repeat unit, about 1.77 thioether groups per anhydroglucose repeat unit, about 1.78 thioether groups per anhydroglucose repeat unit, about 1.79 thioether groups per anhydroglucose repeat unit, about 1.8 thioether groups per anhydroglucose repeat unit, about 1.81 thioether groups per anhydroglucose repeat unit, about 1.82 thioether groups per anhydroglucose repeat unit, about 1.83 thioether groups per anhydroglucose repeat unit, about 1.84 thioether groupsAttorney Docket No. 701586-000154WOPTper anhydroglucose repeat unit, about 1.85 thioether groups per anhydroglucose repeat unit, about 1.86 thioether groups per anhydroglucose repeat unit, about 1.87 thioether groups per anhydroglucose repeat unit, about 1.88 thioether groups per anhydroglucose repeat unit, about 1.89 thioether groups per anhydroglucose repeat unit, about 1.9 thioether groups per anhydroglucose repeat unit, about 1.91 thioether groups per anhydroglucose repeat unit, about 1.92 thioether groups per anhydroglucose repeat unit, about 1.93 thioether groups per anhydroglucose repeat unit, about 1.94 thioether groups per anhydroglucose repeat unit, about 1.95 thioether groups per anhydroglucose repeat unit, about 1.96 thioether groups per anhydroglucose repeat unit, about 1.97 thioether groups per anhydroglucose repeat unit, about 1.98 thioether groups per anhydroglucose repeat unit, about 1.99 thioether groups per anhydroglucose repeat unit, or about 2 thioether groups per anhydroglucose repeat unit.

[0078] In some embodiments of any of the aspects, each anhydroglucose repeat unit of the polymer comprises about 0.63 thioether groups.

[0079] Methods for determining the amount of thioether groups per anhydroglucose repeat unit include but are not limited to, Nuclear Magnetic Resonance (NMR) Spectroscopy, Fourier Transform Infrared Spectroscopy (FTIR), and X-Ray Photoelectron Spectroscopy (XPS).

[0080] In some embodiments of any of the aspects, the polymer comprises from about 10 to about 100,000 anhydroglucose repeat units. For example, the polymer comprises from about 10 to about 50,000 anhydroglucose units, from about 10 to about 25,000 anhydroglucose units, from about 10 to about 25,000 anhydroglucose units, from about 10 to about 10,000 anhydroglucose units, from about 10 to about 5,000 anhydrogluclose units, from about 10 to about 2,500 anhydroglucose units, from about 10 to about 1,000 anhydroglucose units, from about 100 to about 80,000 anhydroglucose units, from about 100 to about 60,000 anhydroglucose units, from about 100 to about 40,000 anhydroglucose units, from about 100 to about 20,000 anhydroglucose units, from about 100 to about 7,500 anhydroglucose units, from about 1,000 to about 90,000 anhydroglucose units, from about 1,000 to about 50,000 anhydroglucose units, from about 1,000 to about 30,000 anhydroglucose units, from about 1,000 to about 15,000 anhydroglucose units, from about 1,000 to about 7,000 anhydroglucose units, from about 10,000 to about 100,000 anhydroglucose units, from about 10,000 to about 80,000 anhydroglucose units, from about 10,000 to about 60,000 anhydroglucose units, from about 10,000 to about 40,000 anhydroglucose units, from about 10,000 to about 20,000 anhydroglucose units, from about 30,000 to about 100,000 anhydroglucose units, from about 30,000 to about 95,000 anhydroglucose units, from about 30,000 to about 90,000 anhydroglucose units, from about 30,000 to about 85,000 anhydroglucose units, from about 30,000 to about 80,000 anhydroglucose units, from about 30,000 to about 75,000 anhydroglucose units, from about 30,000 to about 70,000 anhydroglucose units, from about 30,000Attorney Docket No. 701586-000154WOPTto about 65,000 anhydroglucose units, from about 30,000 to about 60,000 anhydroglucose units, from about 30,000 to about 55,000 anhydroglucose units, from about 30,000 to about 50,000 anhydroglucose units, from about 30,000 to about 45,000 anhydroglucose units, from about 30,000 to about 40,000 anhydroglucose units, from about 30,000 to about 35,000 anhydroglucose units, from about 50,000 to about 100,000 anhydroglucose units, from about 50,000 to about 95,000 anhydroglucose units, from about 50,000 to about 90,000 anhydroglucose units, from about 50,000 to about 85,000 anhydroglucose units, from about 50,000 to about 80,000 anhydroglucose units, from about 50,000 to about 75,000 anhydroglucose units, from about 50,000 to about 70,000 anhydroglucose units, from about 50,000 to about 65,000 anhydroglucose units, from about 50,000 to about 60,000 anhydroglucose units, from about 50,000 to about 55,000 anhydroglucose units, from about 75,000 to about 100,000 anhydroglucose units, from about 75,000 to about 95,000 anhydroglucose units, from about 75,000 to about 90,000 anhydroglucose units, from about 75,000 to about 85,000 anhydroglucose units, from about 75,000 to about 80,000 anhydroglucose units, from about 80,000 to about 100,000 anhydroglucose units, from about 80,000 to about 97,500 anhydroglucose units, from about 80,000 to about 95,000 anhydroglucose units, from about 80,000 to about 92,500 anhydroglucose units, from about 80,000 to about 90,000 anhydroglucose units, from about 80,000 to about 87,500 anhydroglucose units, from about 80,000 to about 85,000 anhydroglucose units, or from about 80,000 to about 82,500 anhydroglucose units. In some embodiments, the polymer comprises about 10 anhydroglucose repeat units, about 500 anhydroglucose repeat units, about 1,000 anhydroglucose repeat units, about 1,500 anhydroglucose repeat units, about 2,000 anhydroglucose repeat units, about 2,500 anhydroglucose repeat units, about 3,000 anhydroglucose repeat units, about 3,500 anhydroglucose repeat units, about 4,000 anhydroglucose repeat units, about 4,500 anhydroglucose repeat units, about 5,000 anhydroglucose repeat units, about 5,500 anhydroglucose repeat units, about 6,000 anhydroglucose repeat units, about 6,500 anhydroglucose repeat units, about 7,000 anhydroglucose repeat units, about 7,500 anhydroglucose repeat units, about 8,000 anhydroglucose repeat units, about 8,500 anhydroglucose repeat units, about 9,000 anhydroglucose repeat units, about 9,500 anhydroglucose repeat units, about 10,000 anhydroglucose repeat units, about 10,500 anhydroglucose repeat units, about 11,000 anhydroglucose repeat units, about 11,500 anhydroglucose repeat units, about 12,000 anhydroglucose repeat units, about 12,500 anhydroglucose repeat units, about 13,000 anhydroglucose repeat units, about 13,500 anhydroglucose repeat units, about 14,000 anhydroglucose repeat units, about 14,500 anhydroglucose repeat units, about 15,000 anhydroglucose repeat units, about 15,500 anhydroglucose repeat units, about 16,000 anhydroglucose repeat units, about 16,500 anhydroglucose repeat units, about 17,000 anhydroglucose repeat units, about 17,500 anhydroglucose repeat units, about 18,000Attorney Docket No. 701586-000154WOPTanhydroglucose repeat units, about 18,500 anhydroglucose repeat units, about 19,000 anhydroglucose repeat units, about 19,500 anhydroglucose repeat units, about 20,000 anhydroglucose repeat units, about 20,500 anhydroglucose repeat units, about 21,000 anhydroglucose repeat units, about 21,500 anhydroglucose repeat units, about 22,000 anhydroglucose repeat units, about 22,500 anhydroglucose repeat units, about 23,000 anhydroglucose repeat units, about 23,500 anhydroglucose repeat units, about 24,000 anhydroglucose repeat units, about 24,500 anhydroglucose repeat units, about 25,000 anhydroglucose repeat units, about 25,500 anhydroglucose repeat units, about 26,000 anhydroglucose repeat units, about 26,500 anhydroglucose repeat units, about 27,000 anhydroglucose repeat units, about 27,500 anhydroglucose repeat units, about 28,000 anhydroglucose repeat units, about 28,500 anhydroglucose repeat units, about 29,000 anhydroglucose repeat units, about 29,500 anhydroglucose repeat units, about 30,000 anhydroglucose repeat units, about 30,500 anhydroglucose repeat units, about 31,000 anhydroglucose repeat units, about 31,500 anhydroglucose repeat units, about 32,000 anhydroglucose repeat units, about 32,500 anhydroglucose repeat units, about 33,000 anhydroglucose repeat units, about 33,500 anhydroglucose repeat units, about 34,000 anhydroglucose repeat units, about 34,500 anhydroglucose repeat units, about 35,000 anhydroglucose repeat units, about 35,500 anhydroglucose repeat units, about 36,000 anhydroglucose repeat units, about 36,500 anhydroglucose repeat units, about 37,000 anhydroglucose repeat units, about 37,500 anhydroglucose repeat units, about 38,000 anhydroglucose repeat units, about 38,500 anhydroglucose repeat units, about 39,000 anhydroglucose repeat units, about 39,500 anhydroglucose repeat units, about 40,000 anhydroglucose repeat units, about 40,500 anhydroglucose repeat units, about 41,000 anhydroglucose repeat units, about 41,500 anhydroglucose repeat units, about 42,000 anhydroglucose repeat units, about 42,500 anhydroglucose repeat units, about 43,000 anhydroglucose repeat units, about 43,500 anhydroglucose repeat units, about 44,000 anhydroglucose repeat units, about 44,500 anhydroglucose repeat units, about 45,000 anhydroglucose repeat units, about 45,500 anhydroglucose repeat units, about 46,000 anhydroglucose repeat units, about 46,500 anhydroglucose repeat units, about 47,000 anhydroglucose repeat units, about 47,500 anhydroglucose repeat units, about 48,000 anhydroglucose repeat units, about 48,500 anhydroglucose repeat units, about 49,000 anhydroglucose repeat units, about 49,500 anhydroglucose repeat units, about 50,000 anhydroglucose repeat units, about 50,500 anhydroglucose repeat units, about 51,000 anhydroglucose repeat units, about 51,500 anhydroglucose repeat units, about 52,000 anhydroglucose repeat units, about 52,500 anhydroglucose repeat units, about 53,000Attorney Docket No. 701586-000154WOPTanhydroglucose repeat units, about 53,500 anhydroglucose repeat units, about 54,000 anhydroglucose repeat units, about 54,500 anhydroglucose repeat units, about 55,000 anhydroglucose repeat units, about 55,500 anhydroglucose repeat units, about 56,000 anhydroglucose repeat units, about 56,500 anhydroglucose repeat units, about 57,000 anhydroglucose repeat units, about 57,500 anhydroglucose repeat units, about 58,000 anhydroglucose repeat units, about 58,500 anhydroglucose repeat units, about 59,000 anhydroglucose repeat units, about 59,500 anhydroglucose repeat units, about 60,000 anhydroglucose repeat units, about 60,500 anhydroglucose repeat units, about 61,000 anhydroglucose repeat units, about 61,500 anhydroglucose repeat units, about 62,000 anhydroglucose repeat units, about 62,500 anhydroglucose repeat units, about 63,000 anhydroglucose repeat units, about 63,500 anhydroglucose repeat units, about 64,000 anhydroglucose repeat units, about 64,500 anhydroglucose repeat units, about 65,000 anhydroglucose repeat units, about 65,500 anhydroglucose repeat units, about 66,000 anhydroglucose repeat units, about 66,500 anhydroglucose repeat units, about 67,000 anhydroglucose repeat units, about 67,500 anhydroglucose repeat units, about 68,000 anhydroglucose repeat units, about 68,500 anhydroglucose repeat units, about 69,000 anhydroglucose repeat units, about 69,500 anhydroglucose repeat units, about 70,000 anhydroglucose repeat units, about 70,500 anhydroglucose repeat units, about 71,000 anhydroglucose repeat units, about 71,500 anhydroglucose repeat units, about 72,000 anhydroglucose repeat units, about 72,500 anhydroglucose repeat units, about 73,000 anhydroglucose repeat units, about 73,500 anhydroglucose repeat units, about 74,000 anhydroglucose repeat units, about 74,500 anhydroglucose repeat units, about 75,000 anhydroglucose repeat units, about 75,500 anhydroglucose repeat units, about 76,000 anhydroglucose repeat units, about 76,500 anhydroglucose repeat units, about 77,000 anhydroglucose repeat units, about 77,500 anhydroglucose repeat units, about 78,000 anhydroglucose repeat units, about 78,500 anhydroglucose repeat units, about 79,000 anhydroglucose repeat units, about 79,500 anhydroglucose repeat units, about 80,000 anhydroglucose repeat units, about 80,500 anhydroglucose repeat units, about 81,000 anhydroglucose repeat units, about 81,500 anhydroglucose repeat units, about 82,000 anhydroglucose repeat units, about 82,500 anhydroglucose repeat units, about 83,000 anhydroglucose repeat units, about 83,500 anhydroglucose repeat units, about 84,000 anhydroglucose repeat units, about 84,500 anhydroglucose repeat units, about 85,000 anhydroglucose repeat units, about 85,500 anhydroglucose repeat units, about 86,000 anhydroglucose repeat units, about 86,500 anhydroglucose repeat units, about 87,000 anhydroglucose repeat units, about 87,500 anhydroglucose repeat units, about 88,000Attorney Docket No. 701586-000154WOPTanhydroglucose repeat units, about 88,500 anhydroglucose repeat units, about 89,000 anhydroglucose repeat units, about 89,500 anhydroglucose repeat units, about 90,000 anhydroglucose repeat units, about 90,500 anhydroglucose repeat units, about 91,000 anhydroglucose repeat units, about 91,500 anhydroglucose repeat units, about 92,000 anhydroglucose repeat units, about 92,500 anhydroglucose repeat units, about 93,000 anhydroglucose repeat units, about 93,500 anhydroglucose repeat units, about 94,000 anhydroglucose repeat units, about 94,500 anhydroglucose repeat units, about 95,000 anhydroglucose repeat units, about 95,500 anhydroglucose repeat units, about 96,000 anhydroglucose repeat units, about 96,500 anhydroglucose repeat units, about 97,000 anhydroglucose repeat units, about 97,500 anhydroglucose repeat units, about 98,000 anhydroglucose repeat units, about 98,500 anhydroglucose repeat units, about 99,000 anhydroglucose repeat units, about 99,500 anhydroglucose repeat units, or about 100,000 anhydroglucose repeat units.

[0081] In some embodiments of any of the aspects, the polymer has a molecular weight (MW) of from about 0.5kDa to about 1,000 kDa. For example, the polymer has a molecular weight from about 0.5 kDa to about 700 kDa, from about 0.5 kDa to about 500 kDa, from about 0.5 kDa to about 300 kDa, from about 0.5 kDa to about 100 kDa, from about 0.5 kDa to about 50 kDa, from about 0.5 kDa to about 10 kDa, from about 0.5 kDa to about 5 kDa, from about 0.5 kDa to about 1 kDa, from about 10 kDa to about 1,000 kDa, from about 10 kDa to about 700 kDa, from about 10 kDa to about 500 kDa, from about 10 kDa to about 300 kDa, from about 10 kDa to about 100 kDa, from about 100 kDa to about 1,000 kDa, from about 100 kDa to about 900 kDa, from about 100 kDa to about 800 kDa, from about 100 kDa to about 700 kDa, from about 100 kDa to about 600 kDa, from about 100 kDa to about 500 kDa, from about 100 kDa to about 400 kDa, from about 100 kDa to about 300 kDa, from about 100 kDa to about 200 kDa, from about 500 kDa to about 1,000 kDa, from about 500 kDa to about 950 kDa, from about 500 kDa to about 900 kDa, from about 500 kDa to about 850 kDa, from about 500 kDa to about 800 kDa, from about 500 kDa to about 750 kDa, from about 500 kDa to about700 kDa, from about 500 kDa to about 650 kDa, or from about 500 kDa to about 600 kDa.

[0082] In some embodiments of any of the aspects, the polymer has a molecular weight (MW) of about 10 kDa, about 20 kDa, about 30 kDa, about 40 kDa, about 50 kDa, about 60 kDa, about 70 kDa, about 80 kDa, about 90 kDa, about 100 kDa, about 110 kDa, about 120 kDa, about 130 kDa, about 140 kDa, about 150 kDa, about 160 kDa, about 170 kDa, about 180 kDa, about 190 kDa, about 200 kDa, about 210 kDa, about 220 kDa, about 230 kDa, about 240 kDa, about 250 kDa, about 260 kDa, about 270 kDa, about 280 kDa, about 290 kDa, about 300 kDa, about 310 kDa, about 320 kDa, about 330 kDa, about 340 kDa, about 350 kDa, about 360 kDa, about 370Attorney Docket No. 701586-000154WOPTkDa, about 380 kDa, about 390 kDa, about 400 kDa, about 410 kDa, about 420 kDa, about 430 kDa, about 440 kDa, about 450 kDa, about 460 kDa, about 470 kDa, about 480 kDa, about 490 kDa, about 500 kDa, about 510 kDa, about 520 kDa, about 530 kDa, about 540 kDa, about 550 kDa, about 560 kDa, about 570 kDa, about 580 kDa, about 590 kDa, about 600 kDa, about 610 kDa, about 620 kDa, about 630 kDa, about 640 kDa, about 650 kDa, about 660 kDa, about 670 kDa, about 680 kDa, about 690 kDa, about 700 kDa, about 710 kDa, about 720 kDa, about 730 kDa, about 740 kDa, about 750 kDa, about 760 kDa, about 770 kDa, about 780 kDa, about 790 kDa, about 800 kDa, about 810 kDa, about 820 kDa, about 830 kDa, about 840 kDa, about 850 kDa, about 860 kDa, about 870 kDa, about 880 kDa, about 890 kDa, about 900 kDa, about 910 kDa, about 920 kDa, about 930 kDa, about 940 kDa, about 950 kDa, about 960 kDa, about 970 kDa, about 980 kDa, about 990 kDa, or about 1,000 kDa.

[0083] In some embodiments of any of the aspects the polymer has a molecular weight (MW) of from about 300 kDa to about 500 kDa. For example, the polymer has a molecular weight of about 300 kDa, about 302.5 kDa, about 305 kDa, about 307.5 kDa, about 310 kDa, about 312.5 kDa, about 315 kDa, about 317.5 kDa, about 320 kDa, about 322.5 kDa, about 325 kDa, about 327.5 kDa, about 330 kDa, about 332.5 kDa, about 335 kDa, about 337.5 kDa, about 340 kDa, about 342.5 kDa, about 345 kDa, about 347.5 kDa, about 350 kDa, about 352.5 kDa, about 355 kDa, about 357.5 kDa, about 360 kDa, about 362.5 kDa, about 365 kDa, about 367.5 kDa, about 370 kDa, about 372.5 kDa, about 375 kDa, about 377.5 kDa, about 380 kDa, about 382.5 kDa, about 385 kDa, about 387.5 kDa, about 390 kDa, about 392.5 kDa, about 395 kDa, about 397.5 kDa, about 400 kDa, about 402.5 kDa, about 405 kDa, about 407.5 kDa, about 410 kDa, about 412.5 kDa, about 415 kDa, about 417.5 kDa, about 420 kDa, about 422.5 kDa, about 425 kDa, about 427.5 kDa, about 430 kDa, about 432.5 kDa, about 435 kDa, about 437.5 kDa, about 440 kDa, about 442.5 kDa, about 445 kDa, about 447.5 kDa, about 450 kDa, about 452.5 kDa, about 455 kDa, about 457.5 kDa, about 460 kDa, about 462.5 kDa, about 465 kDa, about 467.5 kDa, about 470 kDa, about 472.5 kDa, about 475 kDa, about 477.5 kDa, about 480 kDa, about 482.5 kDa, about 485 kDa, about 487.5 kDa, about 490 kDa, about 492.5 kDa, about 495 kDa, about 497.5 kDa, or about 500 kDa.

[0084] It is to be understood, the molecular weight can be the peak average molecular weight (A7p), the number average molecular weight (A7n), or the weight average molecular weight (A w). In some embodiments, molecular weight is number average molecular weight (Mn). Exemplary methods for determining the molecular weight of a polymer include, but are not limited to, Gel Permeation Chromatography (GPC) / Size Exclusion Chromatography (SEC), Mass Spectrometry, Dynamic Light Scattering (DLS), Static Light Scattering (SLS), Ultracentrifugation, End-Group Analysis (e.g., by NMR or titration), Membrane Osmometry, Vapor PressureAttorney Docket No. 701586-000154WOPTOsmometry, and Viscometry. In some embodiments, the molecular weight of the polymer is determined by Size-Exclusion Chromatography (SEC).

[0085] In some embodiments of any of the aspects, the polymer has a polymer dispersion Index (PDI) of from about 0.25 to about 5. For example, the polymer has a PDI of about 0.25, about 0.3, about 0.35, about 0.4, about 0.45, about 0.5, about 0.55, about 0.6, about 0.65, about 0.7, about 0.75, about 0.8, about 0.85, about 0.9, about 0.95, about 1, about 1.05, about 1.1, about 1.15, about 1.2, about 1.25, about 1.3, about 1.35, about 1.4, about 1.45, about 1.5, about 1.55, about 1.6, about 1.65, about 1.7, about 1.75, about 1.8, about 1.85, about 1.9, about 1.95, about 2, about 2.05, about 2.1, about 2.15, about 2.2, about 2.25, about 2.3, about 2.35, about 2.4, about 2.45, about 2.5, about 2.55, about 2.6, about 2.65, about 2.7, about 2.75, about 2.8, about 2.85, about 2.9, about 2.95, about 3, about 3.05, about 3.1, about 3.15, about 3.2, about 3.25, about 3.3, about 3.35, about 3.4, about 3.45, about 3.5, about 3.55, about 3.6, about 3.65, about 3.7, about 3.75, about 3.8, about 3.85, about 3.9, about 3.95, about 4, about 4.05, about 4.1, about 4.15, about 4.2, about 4.25, about 4.3, about 4.35, about 4.4, about 4.45, about 4.5, about 4.55, about 4.6, about 4.65, about 4.7, about 4.75, about 4.8, about 4.85, about 4.9, about 4.95, or about 5.

[0086] As used herein, “polymer dispersion index” or “polydispersity index” or “PDI” refers to a measure of the broadness of a polymer’s molecular weight distribution. The PDI is represented mathematically by the ratio PDI = Mw / Mn, wherein Mwis the weight-average molecular weight of the polymer and Mnis the number average molecular weight of the polymer. Exemplary methods for determining the PDI of a polymer include, but are not limited to, Dynamic Light Scattering (DLS), Static Light Scattering (SLS) (e.g., combined with Osmometry), MALDI-TOF Mass Spectrometry, Gel Permeation Chromatography (GPC) / Size Exclusion Chromatography (SEC), Ultracentrifugation, and End-Group Analysis (e.g., by NMR or titration). In some embodiments, the PDI is determined via Dynamic Light Scattering (DLS).

[0087] In some embodiments of any of the aspects, the polymer is substantially transparent or semi-transparent. As used herein, the term “transparent” or “substantially transparent” means a material that transmits more electromagnetic radiation within a specified wavelength range, e.g., ultraviolet (UV), visible (Vis), or infrared (IR) than is blocked by it. Stated in another way, “transparent” means electromagnetic radiation within a specified wavelength range, e.g., ultraviolet (UV), visible (Vis), or infrared (IR) can pass through the material (e.g., polymer) with losses of less than 50%, e.g., less than 45%, less than 40%, less than 35%, less than 30%, less than 25%, less than 20%, less than 15%, less than 10%, or less than 5%. Typically, a transparent material will have an average transmission of from about 90 to 100%, and an opaque material will have an average transmission of from 0 to about 5%.Attorney Docket No. 701586-000154WOPT

[0088] As used herein, “semi-transparent”, means a material which has a transmission intermediate between a transparent material and an opaque material.

[0089] In some embodiments of any one of the aspects, the polymer has a level of transmittance greater than 50%, at a wavelength from about 300 nm to about 900 nm. For example, the polymer has a level of transmittance between about 50% and 100% at a wavelength from about 300 nm to about 900 nm. In some embodiments of any one of the aspects, the polymer has a level of transmittance of about 55%, e.g., about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95% or higher at a wavelength from about 300 nm to about 900 nm. In some preferred embodiments, the polymer has a level of transmittance of about 90% or higher at a wavelength from about 300 nm to about 900 nm.

[0090] In some embodiments of any of the aspects, the polymer is thermally stable. As used herein, “thermally stable” refers to the ability of a material to maintain its properties when exposed to an increase in temperature. Thermal stability can be measured, for example, using Thermal Gravimetric Analysis (TGA) and Differential Scanning Calorimetry (DSC). In some embodiments, the polymer is thermally stable up to 215 °C.

[0091] In some embodiments of any of the aspects, the polymer is hydrophobic. As used herein, “hydrophobic” refers to a material that repels water. In some embodiments of any of the aspects, the polymer has a water contact angle of about 50 degrees or higher. For example, the water contact angle can be about 50 degrees, about 51 degrees, about 52 degrees, about 53 degrees, about 54 degrees, about 55 degrees, about 56 degrees, about 57 degrees, about 58 degrees, about 59 degrees, about 60 degrees, about 61 degrees, about 62 degrees, about 63 degrees, about 64 degrees, about 65 degrees, about 66 degrees, about 67 degrees, about 68 degrees, about 69 degrees, about 70 degrees, about 71 degrees, about 72 degrees, about 73 degrees, about 74 degrees, about 75 degrees, about 76 degrees, about 77 degrees, about 78 degrees, about 79 degrees, about 80 degrees, or higher than 80 degrees.

[0092] As used herein, “water contact angle” refers to the angle between a surface and a sessile droplet on that surface. Generally, the water contact angle can serve as a measure of the hydrophobicity or hydrophilicity of a surface. A low water contact angle indicates a hydrophilic surface, whereas a high water contact angle indicates a hydrophobic surface. One method of measuring water contact angle is through the use of a goniometer.

[0093] In some embodiments of any of the aspects, the polymer is hydrophilic. As used herein, “hydrophilic” refers to a material that attracts water. In some embodiments of any of the aspects, the polymer has a water contact angle of about 40 degrees or lower. For example, the water contact angle can be about 40 degrees, about 39 degrees, about 38 degrees, about 37 degrees, about 36 degrees, about 35 degrees, about 34 degrees, about 33 degrees, about 32 degrees, about 31Attorney Docket No. 701586-000154WOPTdegrees, about 30 degrees, about 29 degrees, about 28 degrees, about 27 degrees, about 26 degrees, about 25 degrees, about 24 degrees, about 23 degrees, about 22 degrees, about 21 degrees, about 20 degrees, about 19 degrees, about 18 degrees, about 17 degrees, about 16 degrees, about 15 degrees, or lower that 15 degrees.

[0094] In some embodiments of any of the aspects, the polymer is biocompatible. As used herein, “biocompatible” generally refers to a material and any metabolites or degradation products thereof that are generally non-toxic to the recipient and do not cause any significant adverse effects to the subject.

[0095] In some embodiments of any of the aspects, the polymer is non-biodegradable or non-resorbable. As used herein, “non-biodegradable” or “non-resorbable” refers to a material that will not degrade or erode under physiologic conditions, and is not absorbed by the recipient or subject.

[0096] In some embodiments of any of the aspects, the polymer is biodegradable. As used herein, “biodegradable” generally refers to a material that will degrade or erode by hydrolysis or enzymatic action under physiologic conditions to smaller units or chemical species that are capable of being metabolized, eliminated, or excreted by the subject. The degradation time is a function of material composition and morphology.

[0097] In some embodiments of any of the aspects, the polymer is non-immunogenic. As used herein, the term "non-immunogenic" means a material, e.g., polymer that does not induce a response by the immune system. In other words, the term “non-immunogenic” refers to a lack of or absence of an immune response above a detectable threshold to a material, e.g., polymer.

[0098] In some embodiments of any of the aspects, the polymer is antifouling. As used herein, the term antifouling refers to a property whereby the build up of inorganic and / or organic species on a surface is reduced or avoided all together. For example, when an antifouling material is applied to s surface, it prevents or minimizes growth of microorganisms on the surface.

[0099] In some embodiments of any one of the aspects, the polymer is a homopolymer. As used herein, the term “homopolymer” refers to a polymer resulting from the polymerization of a single monomer.

[0100] In some embodiments of any of the aspects, the polymer is a copolymer. As used herein, a copolymer is a type of polymer which comprises two or more types of monomer units.

[0101] In some embodiments of any of the aspects, the polymer is a block polymer. As used herein, a block polymer refers to a type of polymer which comprises two or more types of monomer subunits, wherein said monomer subunits are linked together in discrete segments or “blocks”.Attorney Docket No. 701586-000154WOPT

[0102] In another aspect, provided herein is a composition comprising a thioether-functionalized cellulose polymer of any of the embodiments.

[0103] In some embodiments of any of the aspects, the composition further comprises a solvent.

[0104] As used herein, “solvent” refers to any substance capable of dissolving another substance. When the term solvent is used it may refer to at least one solvent or two or more solvents unless specified. As used herein, “solution” refers to a uniformly dispersed mixture at the molecular level or ionic level, of one or more substances (solute) in one or more substances (solvent). A solvent may be polar, non-polar, protic, aprotic, organic, aqueous, green, halogenated, a mixture of multiple solvent types, or comprise more than one of these attributes. A polar solvent is one comprising molecules with an uneven distribution of electron density, whereas a non-polar solvent is one comprising molecules with an even distribution of electron density. A protic solvent is one which is able to donate a proton (H+) from a highly electronegative atom, whereas an aprotic solvent does not act as a hydrogen bond or proton donor. An organic solvent is a carbon-based liquid that can dissolve other organic substances such as oils or fats. An aqueous solvent comprises water. A green solvent is one that is considered an environmentally friendly alternative to a conventional solvent. A halogenated solvent is an organic solvent that contains halogen atoms such as fluorine, chlorine or bromine. In some embodiments of any of the aspects, the solvent is a polar solvent.

[0105] In some embodiments of any of the aspects, the solvent is a non-polar solvent.

[0106] In some embodiments of any of the aspects, the solvent is a mixture of a polar solvent and a non-polar solvent.

[0107] In some embodiments of any of the aspects, solvent is a protic solvent. In some embodiments of any of the aspects, the solvent is an aprotic solvent. In some embodiments of any of the aspects, the solvent is an organic solvent. In some embodiments of any of the aspects, the solvent is an aqueous solvent. In some embodiments of any of the aspects, the solvent is a green solvent. In some embodiments of any of the aspects, the solvent is a halogenated solvent.

[0108] Exemplary solvents include, but are not limited to, acetic acid, acetone, acetonitrile (MeCN), anisole (methoxybenzene), benzene, carbon tetrachloride (CCL), chloroform, chloroform (CHCh), cyclohexane, dichloromethane (CH2CI2), dichloromethane (DCM), diethyl ether, diisopropyl ether, dimethyl sulfoxide (DMSO), dimethyl acetamide (DMAc), dioxane, ethanol, ethyl acetate, formic acid, isopropanol (IP A), methanol, mineral oil, N, N-dimethylformamide (DMF), n-heptane, n-hexane, nitrobenzene, N-methyl-2-pyrrolidone (NMP), n-propanol, octane, pentane, petroleum ether, propylene carbonate, silicone oil (PDMS), styrene, sulfolane, tetrahydrofuran (THF), toluene, water, and xylene (o-, m-, p-). l,l,l,3,3,3-hexafluoro-2-propanol.Attorney Docket No. 701586-000154WOPT

[0109] In some embodiments, the solvent is a green solvent. The term “green solvent” as used here should be understood as an environmentally friendly solvent, e.g., a solvent that complies with at least one of the 12 principles of green chemistry. The term “green solvent” can include, for example oxygen-containing organic solvents. Typically, “green solvents” will be nonhalogenated solvents (e.g. will not contain chlorine and / or fluorine). Examples of green solvents include, but are not limited to, the following: carbonates (e.g. propylene carbonate, dimethyl carbonate, ethylene carbonate, glyceryl carbonate); esters (e.g. methyl acetate, ethylene acetate, glycerol triacetate, ethyl lactate, dimethyl glutarate, valerolactone); ethers (e.g. ethylene glycol methyl ether, 1,3- dioxoloane, cyclopentyl methyl ether, 2 -methyltetrahydrofuran, 2,5-dimethylfuran, 1,2, 3 -trimethoxypropane); alcohols (e.g. ethanol, butanol, 2-methylbutan-2-ol, glycerol, ethylene glycol, polyethylene glycol); limonene; or mixtures thereof.

[0110] In some embodiments of any of the aspects, the polymer is present at a concentration of from about 0.01 to about 90% w / w or w / v of the total composition. For example, the polymer can be present at a concentration of about 0.01% w / w, about 0.5% w / w, about 1% w / w, about 1.5% w / w, about 2% w / w, about 2.5% w / w, about 3% w / w, about 3.5% w / w, about 4% w / w, about 4.5% w / w, about 5% w / w, about 5.5% w / w, about 6% w / w, about 6.5% w / w, about 7% w / w, about 7.5% w / w, about 8% w / w, about 8.5% w / w, about 9% w / w, about 9.5% w / w, about 10% w / w, about 10.5% w / w, about 11% w / w, about 11.5% w / w, about 12% w / w, about 12.5% w / w, about 13% w / w, about 13.5% w / w, about 14% w / w, about 14.5% w / w, about 15% w / w, about 15.5% w / w, about 16% w / w, about 16.5% w / w, about 17% w / w, about 17.5% w / w, about 18% w / w, about 18.5% w / w, about 19% w / w, about 19.5% w / w, about 20% w / w, about 20.5% w / w, about 21% w / w, about 21.5% w / w, about 22% w / w, about 22.5% w / w, about 23% w / w, about 23.5% w / w, about 24% w / w, about 24.5% w / w, about 25% w / w, about 25.5% w / w, about 26% w / w, about 26.5% w / w, about 27% w / w, about 27.5% w / w, about 28% w / w, about 28.5% w / w, about 29% w / w, about 29.5% w / w, about 30% w / w, about 30.5% w / w, about 31% w / w, about 31.5% w / w, about 32% w / w, about 32.5% w / w, about 33% w / w, about 33.5% w / w, about 34% w / w, about 34.5% w / w, about 35% w / w, about 35.5% w / w, about 36% w / w, about 36.5% w / w, about 37% w / w, about 37.5% w / w, about 38% w / w, about 38.5% w / w, about 39% w / w, about 39.5% w / w, about 40% w / w, about 40.5% w / w, about 41% w / w, about 41.5% w / w, about 42% w / w, about 42.5% w / w, about 43% w / w, about 43.5% w / w, about 44% w / w, about 44.5% w / w, about 45% w / w, about 45.5% w / w, about 46% w / w, about 46.5% w / w, about 47% w / w, about 47.5% w / w, about 48% w / w, about 48.5% w / w, about 49% w / w, about 49.5% w / w, about 50% w / w, about 50.5% w / w, about 51% w / w, about 51.5% w / w, about 52% w / w, about 52.5% w / w, about 53% w / w, about 53.5% w / w, about 54% w / w, about 54.5% w / w, about 55% w / w, about 55.5% w / w, about 56% w / w, about 56.5% w / w, about 57% w / w, about 57.5% w / w, about 58% w / w, about 58.5% w / w, about 59% w / w, about 59.5% w / w, about 60% w / w, about 60.5%Attorney Docket No. 701586-000154WOPTw / w, about 61% w / w, about 61.5% w / w, about 62% w / w, about 62.5% w / w, about 63% w / w, about 63.5% w / w, about 64% w / w, about 64.5% w / w, about 65% w / w, about 65.5% w / w, about 66% w / w, about 66.5% w / w, about 67% w / w, about 67.5% w / w, about 68% w / w, about 68.5% w / w, about 69% w / w, about 69.5% w / w, about 70% w / w, about 70.5% w / w, about 71% w / w, about 71.5% w / w, about 72% w / w, about 72.5% w / w, about 73% w / w, about 73.5% w / w, about 74% w / w, about 74.5% w / w, about 75% w / w, about 75.5% w / w, about 76% w / w, about 76.5% w / w, about 77% w / w, about 77.5% w / w, about 78% w / w, about 78.5% w / w, about 79% w / w, about 79.5% w / w, about 80% w / w, about 80.5% w / w, about 81% w / w, about 81.5% w / w, about 82% w / w, about 82.5% w / w, about 83% w / w, about 83.5% w / w, about 84% w / w, about 84.5% w / w, about 85% w / w, about 85.5% w / w, about 86% w / w, about 86.5% w / w, about 87% w / w, about 87.5% w / w, about 88% w / w, about 88.5% w / w, about 89% w / w, about 89.5% w / w, or about 90% w / w.

[0111] In some embodiments, the polymer is present at a concentration of about 0.01% w / v, about 0.5% w / v, about 1% w / v, about 1.5% w / v, about 2% w / v, about 2.5% w / v, about 3% w / v, about 3.5% w / v, about 4% w / v, about 4.5% w / v, about 5% w / v, about 5.5% w / v, about 6% w / v, about 6.5% w / v, about 7% w / v, about 7.5% w / v, about 8% w / v, about 8.5% w / v, about 9% w / v, about 9.5% w / v, about 10% w / v, about 10.5% w / v, about 11% w / v, about 11.5% w / v, about 12% w / v, about 12.5% w / v, about 13% w / v, about 13.5% w / v, about 14% w / v, about 14.5% w / v, about 15% w / v, about 15.5% w / v, about 16% w / v, about 16.5% w / v, about 17% w / v, about 17.5% w / v, about 18% w / v, about 18.5% w / v, about 19% w / v, about 19.5% w / v, about 20% w / v, about 20.5% w / v, about 21% w / v, about 21.5% w / v, about 22% w / v, about 22.5% w / v, about 23% w / v, about 23.5% w / v, about 24% w / v, about 24.5% w / v, about 25% w / v, about 25.5% w / v, about 26% w / v, about 26.5% w / v, about 27% w / v, about 27.5% w / v, about 28% w / v, about 28.5% w / v, about 29% w / v, about 29.5% w / v, about 30% w / v, about 30.5% w / v, about 31% w / v, about 31.5% w / v, about 32% w / v, about 32.5% w / v, about 33% w / v, about 33.5% w / v, about 34% w / v, about 34.5% w / v, about 35% w / v, about 35.5% w / v, about 36% w / v, about 36.5% w / v, about 37% w / v, about 37.5% w / v, about 38% w / v, about 38.5% w / v, about 39% w / v, about 39.5% w / v, about 40% w / v, about 40.5% w / v, about 41% w / v, about 41.5% w / v, about 42% w / v, about 42.5% w / v, about 43% w / v, about 43.5% w / v, about 44% w / v, about 44.5% w / v, about 45% w / v, about 45.5% w / v, about 46% w / v, about 46.5% w / v, about 47% w / v, about 47.5% w / v, about 48% w / v, about 48.5% w / v, about 49% w / v, about 49.5% w / v, about 50% w / v, about 50.5% w / v, about 51% w / v, about 51.5% w / v, about 52% w / v, about 52.5% w / v, about 53% w / v, about 53.5% w / v, about 54% w / v, about 54.5% w / v, about 55% w / v, about 55.5% w / v, about 56% w / v, about 56.5% w / v, about 57% w / v, about 57.5% w / v, about 58% w / v, about 58.5% w / v, about 59% w / v, about 59.5% w / v, about 60% w / v, about 60.5% w / v, about 61% w / v, about 61.5% w / v, about 62% w / v, about 62.5% w / v, about 63% w / v, about 63.5% w / v, about 64% w / v, about 64.5% w / v, about 65% w / v, about 65.5% w / v, aboutAttorney Docket No. 701586-000154WOPT66% w / v, about 66.5% w / v, about 67% w / v, about 67.5% w / v, about 68% w / v, about 68.5% w / v, about 69% w / v, about 69.5% w / v, about 70% w / v, about 70.5% w / v, about 71% w / v, about 71.5% w / v, about 72% w / v, about 72.5% w / v, about 73% w / v, about 73.5% w / v, about 74% w / v, about 74.5% w / v, about 75% w / v, about 75.5% w / v, about 76% w / v, about 76.5% w / v, about 77% w / v, about 77.5% w / v, about 78% w / v, about 78.5% w / v, about 79% w / v, about 79.5% w / v, about 80% w / v, about 80.5% w / v, about 81% w / v, about 81.5% w / v, about 82% w / v, about 82.5% w / v, about 83% w / v, about 83.5% w / v, about 84% w / v, about 84.5% w / v, about 85% w / v, about 85.5% w / v, about 86% w / v, about 86.5% w / v, about 87% w / v, about 87.5% w / v, about 88% w / v, about 88.5% w / v, about 89% w / v, about 89.5% w / v, or about 90% w / v.

[0112] In some embodiments of any of the aspects the polymer is present at a concentration of from about 0.1 to about 50% w / w or w / v of the total composition. For example, the polymer can be present at a concentration of about 0.1% w / w, about 0.25% w / w, about 0.5% w / w, about 0.75% w / w, about 1% w / w, about 1.25% w / w, about 1.5% w / w, about 1.75% w / w, about 2% w / w, about 2.25% w / w, about 2.5% w / w, about 2.75% w / w, about 3% w / w, about 3.25% w / w, about 3.5% w / w, about 3.75% w / w, about 4% w / w, about 4.25% w / w, about 4.5% w / w, about 4.75% w / w, about 5% w / w, about 5.25% w / w, about 5.5% w / w, about 5.75% w / w, about 6% w / w, about 6.25% w / w, about 6.5% w / w, about 6.75% w / w, about 7% w / w, about 7.25% w / w, about 7.5% w / w, about 7.75% w / w, about 8% w / w, about 8.25% w / w, about 8.5% w / w, about 8.75% w / w, about 9% w / w, about 9.25% w / w, about 9.5% w / w, about 9.75% w / w, about 10% w / w, about 10.25% w / w, about 10.5% w / w, about 10.75% w / w, about 11% w / w, about 11.25% w / w, about 11.5% w / w, about 11.75% w / w, about 12% w / w, about 12.25% w / w, about 12.5% w / w, about 12.75% w / w, about 13% w / w, about 13.25% w / w, about 13.5% w / w, about 13.75% w / w, about 14% w / w, about 14.25% w / w, about 14.5% w / w, about 14.75% w / w, about 15% w / w, about 15.25% w / w, about 15.5% w / w, about 15.75% w / w, about 16% w / w, about 16.25% w / w, about 16.5% w / w, about 16.75% w / w, about 17% w / w, about 17.25% w / w, about 17.5% w / w, about 17.75% w / w, about 18% w / w, about 18.25% w / w, about 18.5% w / w, about 18.75% w / w, about 19% w / w, about 19.25% w / w, about 19.5% w / w, about 19.75% w / w, about 20% w / w, about 20.25% w / w, about 20.5% w / w, about 20.75% w / w, about 21% w / w, about 21.25% w / w, about 21.5% w / w, about 21.75% w / w, about 22% w / w, about 22.25% w / w, about 22.5% w / w, about 22.75% w / w, about 23% w / w, about 23.25% w / w, about 23.5% w / w, about 23.75% w / w, about 24% w / w, about 24.25% w / w, about 24.5% w / w, about 24.75% w / w, about 25% w / w, about 25.25% w / w, about 25.5% w / w, about 25.75% w / w, about 26% w / w, about 26.25% w / w, about 26.5% w / w, about 26.75% w / w, about 27% w / w, about 27.25% w / w, about 27.5% w / w, about 27.75% w / w, about 28% w / w, about 28.25% w / w, about 28.5% w / w, about 28.75% w / w, about 29% w / w, about 29.25% w / w, about 29.5% w / w, about 29.75% w / w, about 30% w / w, about 30.25% w / w, about 30.5% w / w, about 30.75% w / w, about 31% w / w, about 31.25% w / w, about 31.5% w / w, aboutAttorney Docket No. 701586-000154WOPT31.75% w / w, about32%w / w, about 32.25% w / w, about 32.5% w / w, about 32.75% w / w, about33% w / w, about 33.25% w / w, about 33.5% w / w, about 33.75% w / w, about 34% w / w, about 34.25% w / w, about 34.5% w / w, about 34.75% w / w, about 35% w / w, about 35.25% w / w, about 35.5% w / w, about 35.75% w / w, about 36% w / w, about 36.25% w / w, about 36.5% w / w, about 36.75% w / w, about 37% w / w, about 37.25% w / w, about 37.5% w / w, about 37.75% w / w, about 38% w / w, about 38.25% w / w, about 38.5% w / w, about 38.75% w / w, about 39% w / w, about 39.25% w / w, about 39.5% w / w, about 39.75% w / w, about 40% w / w, about 40.25% w / w, about 40.5% w / w, about 40.75% w / w, about 41% w / w, about 41.25% w / w, about 41.5% w / w, about 41.75% w / w, about 42% w / w, about 42.25% w / w, about 42.5% w / w, about 42.75% w / w, about 43% w / w, about 43.25% w / w, about 43.5% w / w, about 43.75% w / w, about 44% w / w, about 44.25% w / w, about 44.5% w / w, about 44.75% w / w, about 45% w / w, about 45.25% w / w, about 45.5% w / w, about 45.75% w / w, about 46% w / w, about 46.25% w / w, about 46.5% w / w, about 46.75% w / w, about 47% w / w, about 47.25% w / w, about 47.5% w / w, about 47.75% w / w, about 48% w / w, about 48.25% w / w, about 48.5% w / w, about 48.75% w / w, about 49% w / w, about 49.25% w / w, about 49.5% w / w, about 49.75% w / w, or about 50% w / w.

[0113] In some embodiments, the polymer is present at a concentration of about 0.1% w / v, about 0.25% w / v, about 0.5% w / v, about 0.75% w / v, about 1% w / v, about 1.25% w / v, about 1.5% w / v, about 1.75% w / v, about 2% w / v, about 2.25% w / v, about 2.5% w / v, about 2.75% w / v, about 3% w / v, about 3.25% w / v, about 3.5% w / v, about 3.75% w / v, about 4% w / v, about 4.25% w / v, about 4.5% w / v, about 4.75% w / v, about 5% w / v, about 5.25% w / v, about 5.5% w / v, about 5.75% w / v, about 6% w / v, about 6.25% w / v, about 6.5% w / v, about 6.75% w / v, about 7% w / v, about 7.25% w / v, about 7.5% w / v, about 7.75% w / v, about 8% w / v, about 8.25% w / v, about 8.5% w / v, about 8.75% w / v, about 9% w / v, about 9.25% w / v, about 9.5% w / v, about 9.75% w / v, about 10% w / v, about 10.25% w / v, about 10.5% w / v, about 10.75% w / v, about 11% w / v, about 11.25% w / v, about 11.5% w / v, about 11.75% w / v, about 12% w / v, about 12.25% w / v, about 12.5% w / v, about 12.75% w / v, about 13% w / v, about 13.25% w / v, about 13.5% w / v, about 13.75% w / v, about 14% w / v, about 14.25% w / v, about 14.5% w / v, about 14.75% w / v, about 15% w / v, about 15.25% w / v, about 15.5% w / v, about 15.75% w / v, about 16% w / v, about 16.25% w / v, about 16.5% w / v, about 16.75% w / v, about 17% w / v, about 17.25% w / v, about 17.5% w / v, about 17.75% w / v, about 18% w / v, about 18.25% w / v, about 18.5% w / v, about 18.75% w / v, about 19% w / v, about 19.25% w / v, about 19.5% w / v, about 19.75% w / v, about 20% w / v, about 20.25% w / v, about 20.5% w / v, about 20.75% w / v, about 21% w / v, about 21.25% w / v, about 21.5% w / v, about 21.75% w / v, about 22% w / v, about 22.25% w / v, about 22.5% w / v, about 22.75% w / v, about 23% w / v, about 23.25% w / v, about 23.5% w / v, about 23.75% w / v, about 24% w / v, about 24.25% w / v, about 24.5% w / v, about 24.75% w / v, about 25% w / v, about 25.25% w / v, about 25.5% w / v, about 25.75% w / v, about 26% w / v, about 26.25% w / v, about 26.5% w / v, about 26.75% w / v, about 27% w / v, about 27.25% w / v, about 27.5%Attorney Docket No. 701586-000154WOPTw / v, about 27.75% w / v, about 28% w / v, about 28.25% w / v, about 28.5% w / v, about 28.75% w / v, about 29% w / v, about 29.25% w / v, about 29.5% w / v, about 29.75% w / v, about 30% w / v, about 30.25% w / v, about 30.5% w / v, about 30.75% w / v, about 31% w / v, about 31.25% w / v, about 31.5% w / v, about 31.75% w / v, about 32% w / v, about 32.25% w / v, about 32.5% w / v, about 32.75% w / v, about 33% w / v, about 33.25% w / v, about 33.5% w / v, about 33.75% w / v, about 34% w / v, about 34.25% w / v, about 34.5% w / v, about 34.75% w / v, about 35% w / v, about 35.25% w / v, about 35.5% w / v, about 35.75% w / v, about 36% w / v, about 36.25% w / v, about 36.5% w / v, about 36.75% w / v, about 37% w / v, about 37.25% w / v, about 37.5% w / v, about 37.75% w / v, about 38% w / v, about 38.25% w / v, about 38.5% w / v, about 38.75% w / v, about 39% w / v, about 39.25% w / v, about 39.5% w / v, about 39.75% w / v, about 40% w / v, about 40.25% w / v, about 40.5% w / v, about 40.75% w / v, about 41% w / v, about 41.25% w / v, about 41.5% w / v, about 41.75% w / v, about 42% w / v, about 42.25% w / v, about 42.5% w / v, about 42.75% w / v, about 43% w / v, about 43.25% w / v, about 43.5% w / v, about 43.75% w / v, about 44% w / v, about 44.25% w / v, about 44.5% w / v, about 44.75% w / v, about 45% w / v, about 45.25% w / v, about 45.5% w / v, about 45.75% w / v, about 46% w / v, about 46.25% w / v, about 46.5% w / v, about 46.75% w / v, about 47% w / v, about 47.25% w / v, about 47.5% w / v, about 47.75% w / v, about 48% w / v, about 48.25% w / v, about 48.5% w / v, about 48.75% w / v, about 49% w / v, about 49.25% w / v, about 49.5% w / v, about 49.75% w / v, or about 50% w / v.

[0114] In some embodiments of any of the aspects the polymer is present at a concentration of from about 0.5 to about 7.5% w / w or w / v of the total composition. For example, the polymer can be present at a concentration of about 0.5% w / w, about 0.55% w / w, about 0.6% w / w, about 0.65% w / w, about 0.7% w / w, about 0.75% w / w, about 0.8% w / w, about 0.85% w / w, about 0.9% w / w, about 0.95% w / w, about 1% w / w, about 1.05% w / w, about 1.1% w / w, about 1.15% w / w, about 1.2% w / w, about 1.25% w / w, about 1.3% w / w, about 1.35% w / w, about 1.4% w / w, about 1.45% w / w, about 1.5% w / w, about 1.55% w / w, about 1.6% w / w, about 1.65% w / w, about 1.7% w / w, about 1.75% w / w, about 1.8% w / w, about 1.85% w / w, about 1.9% w / w, about 1.95% w / w, about 2% w / w, about 2.05% w / w, about 2.1% w / w, about 2.15% w / w, about 2.2% w / w, about 2.25% w / w, about 2.3% w / w, about 2.35% w / w, about 2.4% w / w, about 2.45% w / w, about 2.5% w / w, about 2.55% w / w, about 2.6% w / w, about 2.65% w / w, about 2.7% w / w, about 2.75% w / w, about 2.8% w / w, about 2.85% w / w, about 2.9% w / w, about 2.95% w / w, about 3% w / w, about 3.05% w / w, about 3.1% w / w, about 3.15% w / w, about 3.2% w / w, about 3.25% w / w, about 3.3% w / w, about 3.35% w / w, about 3.4% w / w, about 3.45% w / w, about 3.5% w / w, about 3.55% w / w, about 3.6% w / w, about 3.65% w / w, about 3.7% w / w, about 3.75% w / w, about 3.8% w / w, about 3.85% w / w, about 3.9% w / w, about 3.95% w / w, about 4% w / w, about 4.05% w / w, about 4.1 % w / w, about 4.15% w / w, about 4.2% w / w, about 4.25% w / w, about 4.3% w / w, about 4.35% w / w, about 4.4% w / w, about 4.45% w / w, about 4.5% w / w, about 4.55% w / w, about 4.6% w / w, about 4.65% w / w, about 4.7%Attorney Docket No. 701586-000154WOPTw / w, about 4.75% w / w, about 4.8% w / w, about 4.85% w / w, about 4.9% w / w, about 4.95% w / w, about 5% w / w, about 5.05% w / w, about 5.1% w / w, about 5.15% w / w, about 5.2% w / w, about 5.25% w / w, about 5.3% w / w, about 5.35% w / w, about 5.4% w / w, about 5.45% w / w, about 5.5% w / w, about 5.55% w / w, about 5.6% w / w, about 5.65% w / w, about 5.7% w / w, about 5.75% w / w, about 5.8% w / w, about 5.85% w / w, about 5.9% w / w, about 5.95% w / w, about 6% w / w, about 6.05% w / w, about 6.1% w / w, about 6.15% w / w, about 6.2% w / w, about 6.25% w / w, about 6.3% w / w, about 6.35% w / w, about 6.4% w / w, about 6.45% w / w, about 6.5% w / w, about 6.55% w / w, about 6.6% w / w, about 6.65% w / w, about 6.7% w / w, about 6.75% w / w, about 6.8% w / w, about 6.85% w / w, about 6.9% w / w, about 6.95% w / w, about 7% w / w, about 7.05% w / w, about 7.1% w / w, about 7.15% w / w, about 7.2% w / w, about 7.25% w / w, about 7.3% w / w, about 7.35% w / w, about 7.4% w / w, about 7.45% w / w, or about 7.5% w / w.

[0115] In some embodiments, the polymer is present at a concentration of about 0.5% w / v, about 0.55% w / v, about 0.6% w / v, about 0.65% w / v, about 0.7% w / v, about 0.75% w / v, about 0.8% w / v, about 0.85% w / v, about 0.9% w / v, about 0.95% w / v, about 1% w / v, about 1.05% w / v, about 1.1% w / v, about 1.15% w / v, about 1.2% w / v, about 1.25% w / v, about 1.3% w / v, about 1.35% w / v, about 1.4% w / v, about 1.45% w / v, about 1.5% w / v, about 1.55% w / v, about 1.6% w / v, about 1.65% w / v, about 1.7% w / v, about 1.75% w / v, about 1.8% w / v, about 1.85% w / v, about 1.9% w / v, about 1.95% w / v, about 2% w / v, about 2.05% w / v, about 2.1% w / v, about 2.15% w / v, about 2.2% w / v, about 2.25% w / v, about 2.3% w / v, about 2.35% w / v, about 2.4% w / v, about 2.45% w / v, about 2.5% w / v, about 2.55% w / v, about 2.6% w / v, about 2.65% w / v, about 2.7% w / v, about 2.75% w / v, about 2.8% w / v, about 2.85% w / v, about 2.9% w / v, about 2.95% w / v, about 3% w / v, about 3.05% w / v, about 3.1% w / v, about 3.15% w / v, about 3.2% w / v, about 3.25% w / v, about 3.3% w / v, about 3.35% w / v, about 3.4% w / v, about 3.45% w / v, about 3.5% w / v, about 3.55% w / v, about 3.6% w / v, about 3.65% w / v, about 3.7% w / v, about 3.75% w / v, about 3.8% w / v, about 3.85% w / v, about 3.9% w / v, about 3.95% w / v, about 4% w / v, about 4.05% w / v, about 4.1% w / v, about 4.15% w / v, about 4.2% w / v, about 4.25% w / v, about 4.3% w / v, about 4.35% w / v, about 4.4% w / v, about 4.45% w / v, about 4.5% w / v, about 4.55% w / v, about 4.6% w / v, about 4.65% w / v, about 4.7% w / v, about 4.75% w / v, about 4.8% w / v, about 4.85% w / v, about 4.9% w / v, about 4.95% w / v, about 5% w / v, about 5.05% w / v, about 5.1% w / v, about 5.15% w / v, about 5.2% w / v, about 5.25% w / v, about 5.3% w / v, about 5.35% w / v, about 5.4% w / v, about 5.45% w / v, about 5.5% w / v, about 5.55% w / v, about 5.6% w / v, about 5.65% w / v, about 5.7% w / v, about 5.75% w / v, about 5.8% w / v, about 5.85% w / v, about 5.9% w / v, about 5.95% w / v, about 6% w / v, about 6.05% w / v, about 6.1% w / v, about 6.15% w / v, about 6.2% w / v, about 6.25% w / v, about 6.3% w / v, about 6.35% w / v, about 6.4% w / v, about 6.45% w / v, about 6.5% w / v, about 6.55% w / v, about 6.6% w / v, about 6.65% w / v, about 6.7% w / v, about 6.75% w / v, about 6.8% w / v, about 6.85% w / v, about 6.9% w / v, about 6.95% w / v, about 7% w / v, aboutAttorney Docket No. 701586-000154WOPT7.05% w / v, about 7.1% w / v, about 7.15% w / v, about 7.2% w / v, about 7.25% w / v, about 7.3% w / v, about 7.35% w / v, about 7.4% w / v, about 7.45% w / v, or about 7.5% w / v.

[0116] The amount of the polymer in a composition, e.g., solution can affect the viscosity of the composition. Thus, the composition comprising the polymer can be viscous or non-viscous. As used herein, the term “viscous” means a liquid material, e.g. a solution comprising the polymer, with viscosity of several hundreds centipoises to several millions centipoises. For example, the composition can have a viscosity of from about 0.1 Pa s to about 500 Pa s. In some embodiments of any of the aspects, the composition has a viscosity of from about 0.01 to about 250 Pa s. For example, the composition can have a viscosity from about 0.01 Pa s to about 250 Pa s, from about 0.01 Pa s to about 230 Pa s, from about 0.01 Pa s to about 210 Pa s, from about 0.01 Pa s to about 190 Pa s, from about 0.01 Pa s to about 170 Pa s, from about 0.01 Pa s to about 150 Pa s, from about 0.01 Pa s to about 130 Pa s, from about 0.01 Pa s to about 110 Pa s, from about 0.01 Pa s to about 90 Pa s, from about 0.01 Pa s to about 70 Pa s, from about 0.01 Pas to about 50 Pa s, from about 0.01 Pa s to about 30 Pa s, from about 0.01 Pa s to about 10 Pa s, from about 0.05 Pa s to about 250 Pa s, from about 7.55 Pa s to about 250 Pa s, from about 15.05 Pa s to about 250 Pa s, from about 22.55 Pa s to about 250 Pa s, from about 30.05 Pa s to about 250 Pa s, from about 37.55 Pa s to about 250 Pa s, from about 45.05 Pa s to about 250 Pa s, from about 52.55 Pa s to about 250 Pa s, from about 60.05 Pa s to about 250 Pa s, from about 67.55 Pa s to about 250 Pa s, from about 75.05 Pa s to about 250 Pa s, from about 82.55 Pa s to about 250 Pa s, from about 90.05 Pa s to about 250 Pa s, from about 97.55 Pa s to about 250 Pa s, from about 105.05 Pa s to about 250 Pa s, from about 112.55 Pa s to about 250 Pa s, from about 120.05 Pa s to about 250 Pa s, from about 127.55 Pa s to about 250 Pa s, from about 135.05 Pa s to about 250 Pa s, from about 142.55 Pa s to about 250 Pa s, from about 150.05 Pa s to about 250 Pa s, from about 157.55 Pa s to about 250 Pa s, from about 165.05 Pa s to about 250 Pa s, from about 172.55 Pa s to about 250 Pa s, from about 180.05 Pa s to about 250 Pa s, from about 187.55 Pa s to about 250 Pa s, from about 195.05 Pa s to about 250 Pa s, from about 202.55 Pa s to about 250 Pa s, from about 210.05 Pa s to about 250 Pa s, from about 217.55 Pa s to about 250 Pa s, from about 225.05 Pa s to about 250 Pa s, from about 232.55 Pa s to about 250 Pa s, from about 240.05 Pa s to about 250 Pa s, from about 247.55 Pa s to about 250 Pa s, from about 10 Pa s to about 150 Pa s, from about 20 Pa s to about 150 Pa s, from about 30 Pa s to about 150 Pa s, from about 40 Pa s to about 150 Pa s, from about 50 Pa s to about 150 Pa s, from about 60 Pa s to about 150 Pa s, from about 70 Pa s to about 150 Pa s, from about 80 Pa s to about 150 Pa s, from about 90 Pa s to about 150 Pa s, from about 100 Pa s to about 150 Pa s, from about 110 Pa s to about 150 Pa s, from about 120 Pa s to about 150 Pa s, from about 130 Pa s to about 150 Pa s, from about 140 Pa s to about 150 Pa s, from about 100 Pa s to about 250 Pa s, from about 110 Pa s to about 250 Pa s, from about 120 Pa sAttorney Docket No. 701586-000154WOPTto about 250 Pa s, from about 130 Pa s to about 250 Pa s, from about 140 Pa s to about 250 Pa s, from about 150 Pa s to about 250 Pa s, from about 160 Pa s to about 250 Pa s, from about 170 Pa s to about 250 Pa s, from about 180 Pa s to about 250 Pa s, from about 190 Pa s to about 250 Pa s, from about 200 Pa s to about 250 Pa s, from about 210 Pa s to about 250 Pa s, from about 220 Pa s to about 250 Pa s, from about 230 Pa s to about 250 Pa s, or from about 240 Pa s to about 250 Pa s.

[0117] In some embodiments of any one of the aspects, a composition comprising the polymer descried herein can be viscoelastic. As used herein, the term "viscoelastic" refers to a material exhibiting both elastic and viscous characteristics. For example, a viscoelastic material can at least partially return to its original form when an applied stress is released, and the response is time-dependent. In dynamic mechanical characterization, the level of viscoelasticity is proportional to the damping coefficient measured by the tan (delta) of the material. The tan (delta) is generally the ratio of the viscous dissipative loss modulus to the elastic storage modulus. High tan (delta) values can indicate a high viscous component in the material behavior and hence a strong damping to any perturbation will be observed. The measurement of these moduli is described in An Introduction to Rheology, by Bames, H. A., Hutton, J. F., and Walters, K.; Elsevier, Amsterdam (1997).

[0118] In some embodiments of any of the aspects, the composition further comprises a therapeutic agent. As used herein, a “therapeutic agent” is a substance used to influence the outcome of a disease, whether it be to cure, reduce, eliminate (some of) its symptoms, or improve the quality of life.

[0119] Without limitations, the polymer disclosed herein can be formed into films, sheets, meshs, mats, non-woven mats, foams, fibers, gels, cross-linked gels, and / or particles. The polymer disclosed herein can also be included in melts, waxes, and / or viscous liquids. Further, the polymer can be combined with a second polymer, e.g., a polymer not disclosed herein, to form copolymers or mixtures.

[0120] Accordingly, in another aspect provided is a film comprising a thioether-functionalized cellulose polymer of any one of the embodiments.

[0121] As used herein, “film” refers to a thin sheet or layer of material. Film thickness can be determined, for example, using a digital thickness gauge meter, profilometry, ellipsometry, XPS, Scanning Electron Microscopy (SEM), or Atomic Force Microscopy (AFM).

[0122] In some embodiments of any of the aspects, the film has a thickness of from about 1 pm to about 150 pm. For example, the film thickness can be from about 1 pm to about 150 pm, from about 1 pm to about 140 pm, from about 1 pm to about 130 pm, from about 1 pm to about 120 pm, from about 1 pm to about 110 pm, from about 1 pm to about 100 pm, from about 1 pmAttorney Docket No. 701586-000154WOPTto about 90 μm, from about 1 μm to about 80 μm, from about 1 μm to about 70 μm, from about 1 μm to about 60 μm, from about 1 μm to about 50 μm, from about 1 μm to about 40 μm, from about 1 μm to about 30 μm, from about 1 μm to about 20 μm, from about 1 μm to about 10 μm, from about 10 μm to about 100 μm, from about 10 μm to about 95 μm, from about 10 μm to about 90 μm, from about 10 μm to about 85 μm, from about 10 μm to about 80 μm, from about 10 μm to about 75 μm, from about 10 μm to about 70 μm, from about 10 μm to about 65 μm, from about 10 μm to about 60 μm, from about 10 μm to about 55 μm, from about 10 μm to about 50 μm, from about 10 μm to about 45 μm, from about 10 μm to about 40 μm, from about 10 μm to about 35 μm, from about 10 μm to about 30 μm, from about 10 μm to about 25 μm, from about 10 μm to about 20 μm, from about 10 μm to about 15 μm, from about 50 μm to about 150 μm, from about 55 μm to about 150 μm, from about 60 μm to about 150 μm, from about 65 μm to about 150 μm, from about 70 μm to about 150 μm, from about 75 μm to about 150 μm, from about 80 μm to about 150 μm, from about 85 μm to about 150 μm, from about 90 μm to about 150 μm, from about 95 μm to about 150 μm, from about 100 μm to about 150 μm, from about 105 μm to about 150 μm, from about 110 μm to about 150 μm, from about 115 μm to about 150 μm, from about 120 μm to about 150 μm, from about 125 μm to about 150 μm, from about 130 μm to about 150 μm, from about 135 μm to about 150 μm, from about 140 μm to about 150 μm, or from about 145 μm to about 150 μm.

[0123] In some embodiments of any of the aspects, the film has a thickness of about 1 pm, about 2.5 pm, about 5 pm, about 7.5 pm, about 10 pm, about 12.5 pm, about 15 pm, about 17.5 pm, about 20 pm, about 22.5 pm, about 25 pm, about 27.5 pm, about 30 pm, about 32.5 pm, about 35 pm, about 37.5 pm, about 40 pm, about 42.5 pm, about 45 pm, about 47.5 pm, about 50 pm, about 52.5 pm, about 55 pm, about 57.5 pm, about 60 pm, about 62.5 pm, about 65 pm, about 67.5 pm, about 70 pm, about 72.5 pm, about 75 pm, about 77.5 pm, about 80 pm, about 82.5 pm, about 85 pm, about 87.5 pm, about 90 pm, about 92.5 pm, about 95 pm, about 97.5 pm, about 100 pm, about 102.5 pm, about 105 pm, about 107.5 pm, about 110 pm, about 112.5 pm, about 115 pm, about 117.5 pm, about 120 pm, about 122.5 pm, about 125 pm, about 127.5 pm, about 130 pm, about 132.5 pm, about 135 pm, about 137.5 pm, about 140 pm, about 142.5 pm, about 145 pm, about 147.5 pm, or about 150 pm.

[0001] A surface of the film can be smooth or rough. For example, a surface of the film is smooth.

[0002] The term “surface roughness” means unevenness or ruggedness present of the surface of an object at narrow spacing. Surface roughness, often shortened to roughness, is a component of surface texture. It is quantified by the vertical deviations of a real surface from its ideal form. If these deviations are large, the surface is rough; if they are small, the surface is smooth. There areAttorney Docket No. 701586-000154WOPTmany different roughness parameters in use, but Rais by far the most common. Other common parameters include Rz, Rqand Rsk. As used herein the term “smooth surface” is characterized by a surface roughness (Ra) less than or equal to 250 nm.

[0003] A surface of the film can have an average surface roughness (Ra), as measured on a 5 pm* 5 pm area, within a range having a lower limit and / or an upper limit. The range can include or exclude the lower limit and / or the upper limit. The lower limit and / or upper limit can be selected from about 5, about 10, about 15, about 20, about 25, about 30, about 35, about 40, about 45, about 50, about 55, about 60, about 65, about 70, about 75, about 80, about 85, about 90, about 95, about 100, about 105, about 110, about 115, about 120, about 125, about 130, about 135, about 140, about 145, about 150, about 155, about 160, about 165, about 170, about 175, about 180, about 185, about 190, about 195, about 200, about 205, about 210, about 215, about 220, about 225, about 230, about 235, about 240, about 245, and about 250 nm. For example, according to some embodiments, a surface of the fdm have an average surface roughness (Ra) of from about 5 nm to about 50 nm, as measured on a 5 pm x 5 pm area. In some embodiments, a surface of the film can have an average surface roughness of from about 50 nm to about 100 nm, from about 105 nm to about 200 nm, or from about 200 nm to about 250 nm.

[0004] There are known generally two different types of methods for measuring surface roughness: a direct tracer method in which surface roughness of the object is measured directly with a tracer, and an optical method in which light rays are applied to the object surface and its roughness is measured optically by way of reflection or interference of the light rays applied. For example, surface roughness can be determined, using AFM, digital thickness gauge meter, or profilometry.

[0124] In some embodiments of any of the aspects, a surface of the film has an average surface roughness from about 1 nm to about 75 nm. For example, a surface of the film has an average surface roughness of about 1 nm, about 2 nm, about 3 nm, about 4 nm, about 5 nm, about 6 nm, about 7 nm, about 8 nm, about 9 nm, about 10 nm, about 11 nm, about 12 nm, about 13 nm, about 14 nm, about 15 nm, about 16 nm, about 17 nm, about 18 nm, about 19 nm, about 20 nm, about 21 nm, about 22 nm, about 23 nm, about 24 nm, about 25 nm, about 26 nm, about 27 nm, about 28 nm, about 29 nm, about 30 nm, about 31 nm, about 32 nm, about 33 nm, about 34 nm, about 35 nm, about 36 nm, about 37 nm, about 38 nm, about 39 nm, about 40 nm, about 41 nm, about 42 nm, about 43 nm, about 44 nm, about 45 nm, about 46 nm, about 47 nm, about 48 nm, about 49 nm, about 50 nm, about 61 nm, about 62 nm, about 63 nm, about 64 nm, about 65 nm, about 66 nm, about 67 nm, about 68 nm, about 69 nm, about 70 nm, about 71 nm, about 72 nm, about 73 nm, about 74 nm, or about 75 nm.

[0125] In some embodiments of any of the aspects, wherein the film is antifouling.Attorney Docket No. 701586-000154WOPT

[0126] In some embodiments of any of the aspects, the film undergoes a hydrophobic-to-hydrophilic transition at a surface region with minimal bulk swelling, e.g., under physiological conditions. As used herein “bulk swelling” refers to the tendency for a polymer to absorb a compatible liquid (e.g., a solvent), which causes the polymer volume to increase as a result of the liquid penetrating the polymer matrix.

[0127] In some embodiments of any of the aspects, the film has a higher ultimate interfacial shear strength at failure relative to a film of a same cellulose polymer lacking the thioether substituents. As used herein, “interfacial shear strength at failure” refers to the maximum shear stress a material’s interface can withstand before breakage. Shear stress refers to stress applied parallel to a material’s surface. Methods of measuring interfacial shear strength at failure include, for instance, a tensile testing machine (e.g., an Instron Micro-tester).

[0128] In some embodiments of any of the aspects, the film has an ultimate interfacial shear strength at failure is from about 2000 kPa to about 3500 kPa. For example, the film has an ultimate interfacial shear strength at failure from about 2000 kPa to about 3500 kPa, from about 2000 kPa to about 3400 kPa, from about 2000 kPa to about 3300 kPa, from about 2000 kPa to about 3200 kPa, from about 2000 kPa to about 3100 kPa, from about 2000 kPa to about 3000 kPa, from about 2000 kPa to about 2900 kPa, from about 2000 kPa to about 2800 kPa, from about 2000 kPa to about 2700 kPa, from about 2000 kPa to about 2600 kPa, from about 2000 kPa to about 2500 kPa, from about 2000 kPa to about 2400 kPa, from about 2000 kPa to about 2300 kPa, from about 2000 kPa to about 2200 kPa, from about 2000 kPa to about 2100 kPa, from about 2200 kPa to about 3200 kPa, from about 2200 kPa to about 3150 kPa, from about 2200 kPa to about 3100 kPa, from about 2200 kPa to about 3050 kPa, from about 2200 kPa to about 3000 kPa, from about 2200 kPa to about 2950 kPa, from about 2200 kPa to about 2900 kPa, from about 2200 kPa to about 2850 kPa, from about 2200 kPa to about 2800 kPa, from about 2200 kPa to about 2750 kPa, from about 2200 kPa to about 2700 kPa, from about 2200 kPa to about 2650 kPa, from about 2200 kPa to about 2600 kPa, from about 2200 kPa to about 2550 kPa, from about 2200 kPa to about 2500 kPa, from about 2200 kPa to about 2450 kPa, from about 2200 kPa to about 2400 kPa, from about 2200 kPa to about 2350 kPa, from about 2200 kPa to about 2300 kPa, from about 2200 kPa to about 2250 kPa, from about 2000 kPa to about 3500 kPa, from about 2100 kPa to about 3500 kPa, from about 2200 kPa to about 3500 kPa, from about 2300 kPa to about 3500 kPa, from about 2400 kPa to about 3500 kPa, from about 2500 kPa to about 3500 kPa, from about 2600 kPa to about 3500 kPa, from about 2700 kPa to about 3500 kPa, from about 2800 kPa to about 3500 kPa, from about 2900 kPa to about 3500 kPa, from about 3000 kPa to about 3500 kPa, from about 3100 kPa to about 3500 kPa, from about 3200 kPa to about 3500 kPa, from about 3300 kPa to about 3500 kPa, or from about 3400 kPa to about 3500 kPa.Attorney Docket No. 701586-000154WOPT

[0129] In some embodiments of any of the aspects, the film has an ultimate interfacial shear strength at failure of about 2000 kPa, about 2025 kPa, about 2050 kPa, about 2075 kPa, about 2100 kPa, about 2125 kPa, about 2150 kPa, about 2175 kPa, about 2200 kPa, about 2225 kPa, about 2250 kPa, about 2275 kPa, about 2300 kPa, about 2325 kPa, about 2350 kPa, about 2375 kPa, about 2400 kPa, about 2425 kPa, about 2450 kPa, about 2475 kPa, about 2500 kPa, about 2525 kPa, about 2550 kPa, about 2575 kPa, about 2600 kPa, about 2625 kPa, about 2650 kPa, about 2675 kPa, about 2700 kPa, about 2725 kPa, about 2750 kPa, about 2775 kPa, about 2800 kPa, about 2825 kPa, about 2850 kPa, about 2875 kPa, about 2900 kPa, about 2925 kPa, about 2950 kPa, about 2975 kPa, about 3000 kPa, about 3025 kPa, about 3050 kPa, about 3075 kPa, about 3100 kPa, about 3125 kPa, about 3150 kPa, about 3175 kPa, about 3200 kPa, about 3225 kPa, about 3250 kPa, about 3275 kPa, about 3300 kPa, about 3325 kPa, about 3350 kPa, about 3375 kPa, about 3400 kPa, about 3425 kPa, about 3450 kPa, about 3475 kPa, or about 3500 kPa.

[0130] In some embodiments of any of the aspects, the film has an elastic modulus of from about 200 MPa to about 500 MPa in a dry state. As used herein, “elastic modulus” refers to a material’s ability to resist elastic deformation. The elastic modulus, also referred to herein as the Young’s modulus, is equivalent to stress over strain, and is represented by the slope of a material’s stress vs. strain curve. Elastic modulus can be measured, for instance, using a tensile testing machine (e.g., an Instron Micro-tester).

[0131] In some embodiments of any of the aspects, the film has an ultimate tensile strength of from about 20 MPa to about 50 MPa in a dry state. As used herein, “ultimate tensile strength” refers to the maximum stress a material can withstand while being stretched or pulled before breaking or fracture. Ultimate tensile strength can be measured, for instance, using a tensile testing machine (e.g., an Instron Micro-tester). For example, the ultimate tensile strength of the film in a dry state can be from about 20 MPa to about 50 MPa, from about 20 MPa to about 49 MPa, from about 20 MPa to about 48 MPa, from about 20 MPa to about 47 MPa, from about 20 MPa to about 46 MPa, from about 20 MPa to about 45 MPa, from about 20 MPa to about 44 MPa, from about 20 MPa to about 43 MPa, from about 20 MPa to about 42 MPa, from about 20 MPa to about 41 MPa, from about 20 MPa to about 40 MPa, from about 20 MPa to about 39 MPa, from about 20 MPa to about 38 MPa, from about 20 MPa to about 37 MPa, from about 20 MPa to about 36 MPa, from about 20 MPa to about 35 MPa, from about 20 MPa to about 34 MPa, from about 20 MPa to about 33 MPa, from about 20 MPa to about 32 MPa, from about 20 MPa to about 31 MPa, from about 20 MPa to about 30 MPa, from about 20 MPa to about 29 MPa, from about 20 MPa to about 28 MPa, from about 20 MPa to about 27 MPa, from about 20 MPa to about 26 MPa, from about 20 MPa to about 25 MPa, from about 20 MPa to about 24 MPa, from about 20 MPa to about 23 MPa, from about 20 MPa to about 22 MPa, from about 20 MPa to about 21 MPa, from about 30Attorney Docket No. 701586-000154WOPTMPa to about 40 MPa, from about 30 MPa to about 39.75 MPa, from about 30 MPa to about 39.5 MPa, from about 30 MPa to about 39.25 MPa, from about 30 MPa to about 39 MPa, from about 30 MPa to about 38.75 MPa, from about 30 MPa to about 38.5 MPa, from about 30 MPa to about 38.25 MPa, from about 30 MPa to about 38 MPa, from about 30 MPa to about 37.75 MPa, from about 30 MPa to about 37.5 MPa, from about 30 MPa to about 37.25 MPa, from about 30 MPa to about 37 MPa, from about 30 MPa to about 36.75 MPa, from about 30 MPa to about 36.5 MPa, from about 30 MPa to about 36.25 MPa, from about 30 MPa to about 36 MPa, from about 30 MPa to about 35.75 MPa, from about 30 MPa to about 35.5 MPa, from about 30 MPa to about 35.25 MPa, from about 30 MPa to about 35 MPa, from about 30 MPa to about 34.75 MPa, from about 30 MPa to about 34.5 MPa, from about 30 MPa to about 34.25 MPa, from about 30 MPa to about 34 MPa, from about 30 MPa to about 33.75 MPa, from about 30 MPa to about 33.5 MPa, from about 30 MPa to about 33.25 MPa, from about 30 MPa to about 33 MPa, from about 30 MPa to about 32.75 MPa, from about 30 MPa to about 32.5 MPa, from about 30 MPa to about 32.25 MPa, from about 30 MPa to about 32 MPa, from about 30 MPa to about 31.75 MPa, from about 30 MPa to about 31.5 MPa, from about 30 MPa to about 31.25 MPa, from about 30 MPa to about 31 MPa, from about 30 MPa to about 30.75 MPa, from about 30 MPa to about 30.5 MPa, from about 30 MPa to about 30.25 MPa, from about 20 MPa to about 50 MPa, from about 21 MPa to about 50 MPa, from about 22 MPa to about 50 MPa, from about 23 MPa to about 50 MPa, from about 24 MPa to about 50 MPa, from about 25 MPa to about 50 MPa, from about 26 MPa to about 50 MPa, from about 27 MPa to about 50 MPa, from about 28 MPa to about 50 MPa, from about 29 MPa to about 50 MPa, from about 30 MPa to about 50 MPa, from about 31 MPa to about 50 MPa, from about 32 MPa to about 50 MPa, from about 33 MPa to about 50 MPa, from about 34 MPa to about 50 MPa, from about 35 MPa to about 50 MPa, from about 36 MPa to about 50 MPa, from about 37 MPa to about 50 MPa, from about 38 MPa to about 50 MPa, from about 39 MPa to about 50 MPa, from about 40 MPa to about 50 MPa, from about 41 MPa to about 50 MPa, from about 42 MPa to about 50 MPa, from about 43 MPa to about 50 MPa, from about 44 MPa to about 50 MPa, from about 45 MPa to about 50 MPa, from about 46 MPa to about 50 MPa, from about 47 MPa to about 50 MPa, from about 48 MPa to about 50 MPa, or from about 49 MPa to about 50 MPa.

[0132] In some embodiments of any of the aspects, the film has an ultimate tensile strength of about 20 MPa, about 21 MPa, about 22 MPa, about 23 MPa, about 24 MPa, about 25 MPa, about 26 MPa, about 27 MPa, about 28 MPa, about 29 MPa, about 30 MPa, about 31 MPa, about 32 MPa, about 33 MPa, about 34 MPa, about 35 MPa, about 36 MPa, about 37 MPa, about 38 MPa, about 39 MPa, about 40 MPa, about 41 MPa, about 42 MPa, about 43 MPa, about 44 MPa, about 45 MPa, about 46 MPa, about 47 MPa, about 48 MPa, about 49 MPa, or about 50 MPa in a dry state.Attorney Docket No. 701586-000154WOPT

[0133] In some embodiments of any of the aspects, the film has an elastic modulus of from about 500 MPa to about 750 MPa in a hydrated state. For example, the film can have an elastic modulus of from about 500 MPa to about 750 MPa, from about 500 MPa to about 740 MPa, from about 500 MPa to about 730 MPa, from about 500 MPa to about 720 MPa, from about 500 MPa to about 710 MPa, from about 500 MPa to about 700 MPa, from about 500 MPa to about 690 MPa, from about 500 MPa to about 680 MPa, from about 500 MPa to about 670 MPa, from about 500 MPa to about 660 MPa, from about 500 MPa to about 650 MPa, from about 500 MPa to about 640 MPa, from about 500 MPa to about 630 MPa, from about 500 MPa to about 620 MPa, from about 500 MPa to about 610 MPa, from about 500 MPa to about 600 MPa, from about 500 MPa to about 590 MPa, from about 500 MPa to about 580 MPa, from about 500 MPa to about 570 MPa, from about 500 MPa to about 560 MPa, from about 500 MPa to about 550 MPa, from about 500 MPa to about 540 MPa, from about 500 MPa to about 530 MPa, from about 500 MPa to about 520 MPa, from about 500 MPa to about 510 MPa, from about 575 MPa to about 675 MPa, from about 575 MPa to about 670 MPa, from about 575 MPa to about 665 MPa, from about 575 MPa to about 660 MPa, from about 575 MPa to about 655 MPa, from about 575 MPa to about 650 MPa, from about 575 MPa to about 645 MPa, from about 575 MPa to about 640 MPa, from about 575 MPa to about 635 MPa, from about 575 MPa to about 630 MPa, from about 575 MPa to about 625 MPa, from about 575 MPa to about 620 MPa, from about 575 MPa to about 615 MPa, from about 575 MPa to about 610 MPa, from about 575 MPa to about 605 MPa, from about 575 MPa to about 600 MPa, from about 575 MPa to about 595 MPa, from about 575 MPa to about 590 MPa, from about 575 MPa to about 585 MPa, from about 575 MPa to about 580 MPa, from about 510 MPa to about 750 MPa, from about 520 MPa to about 750 MPa, from about 530 MPa to about 750 MPa, from about 540 MPa to about 750 MPa, from about 550 MPa to about 750 MPa, from about 560 MPa to about 750 MPa, from about 570 MPa to about 750 MPa, from about 580 MPa to about 750 MPa, from about 590 MPa to about 750 MPa, from about 600 MPa to about 750 MPa, from about 610 MPa to about 750 MPa, from about 620 MPa to about 750 MPa, from about 630 MPa to about 750 MPa, from about 640 MPa to about 750 MPa, from about 650 MPa to about 750 MPa, from about 660 MPa to about 750 MPa, from about 670 MPa to about 750 MPa, from about 680 MPa to about 750 MPa, from about 690 MPa to about 750 MPa, from about 700 MPa to about 750 MPa, from about 710 MPa to about 750 MPa, from about 720 MPa to about 750 MPa, from about 730 MPa to about 750 MPa, or from about 740 MPa to about 750 MPa.

[0134] In some embodiments of any of the aspects, the film has an elastic modulus of about 500 MPa, about 505 MPa, about 510 MPa, about 515 MPa, about 520 MPa, about 525 MPa, about 530 MPa, about 535 MPa, about 540 MPa, about 545 MPa, about 550 MPa, about 555 MPa, about 560 MPa, about 565 MPa, about 570 MPa, about 575 MPa, about 580 MPa, about 585 MPa, aboutAttorney Docket No. 701586-000154WOPT590 MPa, about 595 MPa, about 600 MPa, about 605 MPa, about 610 MPa, about 615 MPa, about 620 MPa, about 625 MPa, about 630 MPa, about 635 MPa, about 640 MPa, about 645 MPa, about 650 MPa, about 655 MPa, about 660 MPa, about 665 MPa, about 670 MPa, about 675 MPa, about 680 MPa, about 685 MPa, about 690 MPa, about 695 MPa, about 700 MPa, about 705 MPa, about 710 MPa, about 715 MPa, about 720 MPa, about 725 MPa, about 730 MPa, about 735 MPa, about 740 MPa, about 745 MPa, or about 750 MPa in a hydrated state.

[0135] In some embodiments of any of the aspects, the film has an ultimate tensile strength of from about 700 MPa to about 1,100 MPa in a hydrated state. For example, the film can have an ultimate tensile strength of from about 700 MPa to about 1100 MPa, from about 725 MPa to about 1100 MPa, from about 750 MPa to about 1100 MPa, from about 775 MPa to about 1100 MPa, from about 800 MPa to about 1100 MPa, from about 825 MPa to about 1100 MPa, from about 850 MPa to about 1100 MPa, from about 875 MPa to about 1100 MPa, from about 900 MPa to about 1100 MPa, from about 925 MPa to about 1100 MPa, from about 950 MPa to about 1100 MPa, from about 975 MPa to about 1100 MPa, from about 1000 MPa to about 1100 MPa, from about 1025 MPa to about 1100 MPa, from about 1050 MPa to about 1100 MPa, from about 1075 MPa to about 1100 MPa, from about 800 MPa to about 1000 MPa, from about 820 MPa to about 1000 MPa, from about 840 MPa to about 1000 MPa, from about 860 MPa to about 1000 MPa, from about 880 MPa to about 1000 MPa, from about 900 MPa to about 1000 MPa, from about 920 MPa to about 1000 MPa, from about 940 MPa to about 1000 MPa, from about 960 MPa to about 1000 MPa, from about 980 MPa to about 1000 MPa, from about 700 MPa to about 1075 MPa, from about 700 MPa to about 1050 MPa, from about 700 MPa to about 1025 MPa, from about 700 MPa to about 1000 MPa, from about 700 MPa to about 975 MPa, from about 700 MPa to about 950 MPa, from about 700 MPa to about 925 MPa, from about 700 MPa to about 900 MPa, from about 700 MPa to about 875 MPa, from about 700 MPa to about 850 MPa, from about 700 MPa to about 825 MPa, from about 700 MPa to about 800 MPa, from about 700 MPa to about 775 MPa, from about 700 MPa to about 750 MPa, or from about 700 MPa to about 725 MPa in a hydrated state.

[0136] In some embodiments of any of the aspects, the film has an ultimate tensile strength of about 700 MPa, about 705 MPa, about 710 MPa, about 715 MPa, about 720 MPa, about 725 MPa, about 730 MPa, about 735 MPa, about 740 MPa, about 745 MPa, about 750 MPa, about 755 MPa, about 760 MPa, about 765 MPa, about 770 MPa, about 775 MPa, about 780 MPa, about 785 MPa, about 790 MPa, about 795 MPa, about 800 MPa, about 805 MPa, about 810 MPa, about 815 MPa, about 820 MPa, about 825 MPa, about 830 MPa, about 835 MPa, about 840 MPa, about 845 MPa, about 850 MPa, about 855 MPa, about 860 MPa, about 865 MPa, about 870 MPa, about 875 MPa, about 880 MPa, about 885 MPa, about 890 MPa, about 895 MPa, about 900 MPa, about 905 MPa, about 910 MPa, about 915 MPa, about 920 MPa, about 925 MPa, about 930 MPa, about 935Attorney Docket No. 701586-000154WOPTMPa, about 940 MPa, about 945 MPa, about 950 MPa, about 955 MPa, about 960 MPa, about 965 MPa, about 970 MPa, about 975 MPa, about 980 MPa, about 985 MPa, about 990 MPa, about 995 MPa, about 1000 MPa, about 1005 MPa, about 1010 MPa, about 1015 MPa, about 1020 MPa, about 1025 MPa, about 1030 MPa, about 1035 MPa, about 1040 MPa, about 1045 MPa, about 1050 MPa, about 1055 MPa, about 1060 MPa, about 1065 MPa, about 1070 MPa, about 1075 MPa, about 1080 MPa, about 1085 MPa, about 1090 MPa, about 1095 MPa, or about 1100 MPa.

[0137] In some embodiments of any of the aspects, the film has a surface elastic modulus of from about 200 kPa to about 700 kPa in an oxidized state. For example, the film can have a surface elastic modulus of from about 200 kPa to about 700 kPa, from about 210 kPa to about 700 kPa, from about 220 kPa to about 700 kPa, from about 230 kPa to about 700 kPa, from about 240 kPa to about 700 kPa, from about 250 kPa to about 700 kPa, from about 260 kPa to about 700 kPa, from about 270 kPa to about 700 kPa, from about 280 kPa to about 700 kPa, from about 290 kPa to about 700 kPa, from about 300 kPa to about 700 kPa, from about 310 kPa to about 700 kPa, from about 320 kPa to about 700 kPa, from about 330 kPa to about 700 kPa, from about 340 kPa to about 700 kPa, from about 350 kPa to about 700 kPa, from about 360 kPa to about 700 kPa, from about 370 kPa to about 700 kPa, from about 380 kPa to about 700 kPa, from about 390 kPa to about 700 kPa, from about 400 kPa to about 700 kPa, from about 410 kPa to about 700 kPa, from about 420 kPa to about 700 kPa, from about 430 kPa to about 700 kPa, from about 440 kPa to about 700 kPa, from about 450 kPa to about 700 kPa, from about 460 kPa to about 700 kPa, from about 470 kPa to about 700 kPa, from about 480 kPa to about 700 kPa, from about 490 kPa to about 700 kPa, from about 500 kPa to about 700 kPa, from about 510 kPa to about 700 kPa, from about 520 kPa to about 700 kPa, from about 530 kPa to about 700 kPa, from about 540 kPa to about 700 kPa, from about 550 kPa to about 700 kPa, from about 560 kPa to about 700 kPa, from about 570 kPa to about 700 kPa, from about 580 kPa to about 700 kPa, from about 590 kPa to about 700 kPa, from about 600 kPa to about 700 kPa, from about 610 kPa to about 700 kPa, from about 620 kPa to about 700 kPa, from about 630 kPa to about 700 kPa, from about 640 kPa to about 700 kPa, from about 650 kPa to about 700 kPa, from about 660 kPa to about 700 kPa, from about 670 kPa to about 700 kPa, from about 680 kPa to about 700 kPa, from about 690 kPa to about 700 kPa, from about 300 kPa to about 600 kPa, from about 310 kPa to about 600 kPa, from about 320 kPa to about 600 kPa, from about 330 kPa to about 600 kPa, from about 340 kPa to about 600 kPa, from about 350 kPa to about 600 kPa, from about 360 kPa to about 600 kPa, from about 370 kPa to about 600 kPa, from about 380 kPa to about 600 kPa, from about 390 kPa to about 600 kPa, from about 400 kPa to about 600 kPa, from about 410 kPa to about 600 kPa, from about 420 kPa to about 600 kPa, from about 430 kPa to about 600 kPa, from about 440 kPa to about 600 kPa, from about 450 kPa to about 600 kPa, from about 460 kPa to about 600 kPa,Attorney Docket No. 701586-000154WOPTfrom about 470 kPa to about 600 kPa, from about 480 kPa to about 600 kPa, from about 490 kPa to about 600 kPa, from about 500 kPa to about 600 kPa, from about 510 kPa to about 600 kPa, from about 520 kPa to about 600 kPa, from about 530 kPa to about 600 kPa, from about 540 kPa to about 600 kPa, from about 550 kPa to about 600 kPa, from about 560 kPa to about 600 kPa, from about 570 kPa to about 600 kPa, from about 580 kPa to about 600 kPa, from about 590 kPa to about 600 kPa, from about 400 kPa to about 500 kPa, from about 400 kPa to about 498 kPa, from about 400 kPa to about 496 kPa, from about 400 kPa to about 494 kPa, from about 400 kPa to about 492 kPa, from about 400 kPa to about 490 kPa, from about 400 kPa to about 488 kPa, from about 400 kPa to about 486 kPa, from about 400 kPa to about 484 kPa, from about 400 kPa to about 482 kPa, from about 400 kPa to about 480 kPa, from about 400 kPa to about 478 kPa, from about 400 kPa to about 476 kPa, from about 400 kPa to about 474 kPa, from about 400 kPa to about 472 kPa, from about 400 kPa to about 470 kPa, from about 400 kPa to about 468 kPa, from about 400 kPa to about 466 kPa, from about 400 kPa to about 464 kPa, from about 400 kPa to about 462 kPa, from about 400 kPa to about 460 kPa, from about 400 kPa to about 458 kPa, from about 400 kPa to about 456 kPa, from about 400 kPa to about 454 kPa, from about 400 kPa to about 452 kPa, from about 400 kPa to about 450 kPa, from about 400 kPa to about 448 kPa, from about 400 kPa to about 446 kPa, from about 400 kPa to about 444 kPa, from about 400 kPa to about 442 kPa, from about 400 kPa to about 440 kPa, from about 400 kPa to about 438 kPa, from about 400 kPa to about 436 kPa, from about 400 kPa to about 434 kPa, from about 400 kPa to about 432 kPa, from about 400 kPa to about 430 kPa, from about 400 kPa to about 428 kPa, from about 400 kPa to about 426 kPa, from about 400 kPa to about 424 kPa, from about 400 kPa to about 422 kPa, from about 400 kPa to about 420 kPa, from about 400 kPa to about 418 kPa, from about 400 kPa to about 416 kPa, from about 400 kPa to about 414 kPa, from about 400 kPa to about 412 kPa, from about 400 kPa to about 410 kPa, from about 400 kPa to about 408 kPa, from about 400 kPa to about 406 kPa, from about 400 kPa to about 404 kPa, from about 400 kPa to about 402 kPa, from about 200 kPa to about 700 kPa, from about 200 kPa to about 680 kPa, from about 200 kPa to about 660 kPa, from about 200 kPa to about 640 kPa, from about 200 kPa to about 620 kPa, from about 200 kPa to about 600 kPa, from about 200 kPa to about 580 kPa, from about 200 kPa to about 560 kPa, from about 200 kPa to about 540 kPa, from about 200 kPa to about 520 kPa, from about 200 kPa to about 500 kPa, from about 200 kPa to about 480 kPa, from about 200 kPa to about 460 kPa, from about 200 kPa to about 440 kPa, from about 200 kPa to about 420 kPa, from about 200 kPa to about 400 kPa, from about 200 kPa to about 380 kPa, from about 200 kPa to about 360 kPa, from about 200 kPa to about 340 kPa, from about 200 kPa to about 320 kPa, from about 200 kPa to about 300 kPa, from about 200 kPa to about 280 kPa,Attorney Docket No. 701586-000154WOPTfrom about 200 kPa to about 260 kPa, from about 200 kPa to about 240 kPa, or from about 200 kPa to about 220 kPa in an oxidized state.

[0138] In some embodiments of any of the aspects, the fdm has a surface elastic modulus of about 200 kPa, about 202.5 kPa, about 205 kPa, about 207.5 kPa, about 210 kPa, about 212.5 kPa, about 215 kPa, about 217.5 kPa, about 220 kPa, about 222.5 kPa, about 225 kPa, about 227.5 kPa, about 230 kPa, about 232.5 kPa, about 235 kPa, about 237.5 kPa, about 240 kPa, about 242.5 kPa, about 245 kPa, about 247.5 kPa, about 250 kPa, about 252.5 kPa, about 255 kPa, about 257.5 kPa, about 260 kPa, about 262.5 kPa, about 265 kPa, about 267.5 kPa, about 270 kPa, about 272.5 kPa, about 275 kPa, about 277.5 kPa, about 280 kPa, about 282.5 kPa, about 285 kPa, about 287.5 kPa, about 290 kPa, about 292.5 kPa, about 295 kPa, about 297.5 kPa, about 300 kPa, about 302.5 kPa, about 305 kPa, about 307.5 kPa, about 310 kPa, about 312.5 kPa, about 315 kPa, about 317.5 kPa, about 320 kPa, about 322.5 kPa, about 325 kPa, about 327.5 kPa, about 330 kPa, about 332.5 kPa, about 335 kPa, about 337.5 kPa, about 340 kPa, about 342.5 kPa, about 345 kPa, about 347.5 kPa, about 350 kPa, about 352.5 kPa, about 355 kPa, about 357.5 kPa, about 360 kPa, about 362.5 kPa, about 365 kPa, about 367.5 kPa, about 370 kPa, about 372.5 kPa, about 375 kPa, about 377.5 kPa, about 380 kPa, about 382.5 kPa, about 385 kPa, about 387.5 kPa, about 390 kPa, about 392.5 kPa, about 395 kPa, about 397.5 kPa, about 400 kPa, about 402.5 kPa, about 405 kPa, about 407.5 kPa, about 410 kPa, about 412.5 kPa, about 415 kPa, about 417.5 kPa, about 420 kPa, about 422.5 kPa, about 425 kPa, about 427.5 kPa, about 430 kPa, about 432.5 kPa, about 435 kPa, about 437.5 kPa, about 440 kPa, about 442.5 kPa, about 445 kPa, about 447.5 kPa, about 450 kPa, about 452.5 kPa, about 455 kPa, about 457.5 kPa, about 460 kPa, about 462.5 kPa, about 465 kPa, about 467.5 kPa, about 470 kPa, about 472.5 kPa, about 475 kPa, about 477.5 kPa, about 480 kPa, about 482.5 kPa, about 485 kPa, about 487.5 kPa, about 490 kPa, about 492.5 kPa, about 495 kPa, about 497.5 kPa, about 500 kPa, about 502.5 kPa, about 505 kPa, about 507.5 kPa, about 510 kPa, about 512.5 kPa, about 515 kPa, about 517.5 kPa, about 520 kPa, about 522.5 kPa, about 525 kPa, about 527.5 kPa, about 530 kPa, about 532.5 kPa, about 535 kPa, about 537.5 kPa, about 540 kPa, about 542.5 kPa, about 545 kPa, about 547.5 kPa, about 550 kPa, about 552.5 kPa, about 555 kPa, about 557.5 kPa, about 560 kPa, about 562.5 kPa, about 565 kPa, about 567.5 kPa, about 570 kPa, about 572.5 kPa, about 575 kPa, about 577.5 kPa, about 580 kPa, about 582.5 kPa, about 585 kPa, about 587.5 kPa, about 590 kPa, about 592.5 kPa, about 595 kPa, about 597.5 kPa, about 600 kPa, about 602.5 kPa, about 605 kPa, about 607.5 kPa, about 610 kPa, about 612.5 kPa, about 615 kPa, about 617.5 kPa, about 620 kPa, about 622.5 kPa, about 625 kPa, about 627.5 kPa, about 630 kPa, about 632.5 kPa, about 635 kPa, about 637.5 kPa, about 640 kPa, about 642.5 kPa, about 645 kPa, about 647.5 kPa, about 650 kPa, about 652.5 kPa, about 655 kPa, about 657.5 kPa, about 660 kPa, about 662.5 kPa, about 665 kPa, about 667.5 kPa, about 670 kPa, about 672.5 kPa, about 675 kPa, about 677.5Attorney Docket No. 701586-000154WOPTkPa, about 680 kPa, about 682.5 kPa, about 685 kPa, about 687.5 kPa, about 690 kPa, about 692.5 kPa, about 695 kPa, about 697.5 kPa, or about 700 kPa in an oxidized state.

[0139] In some embodiments of any of the aspects, the film is substantially transparent or semi-transparent. For example, the film has a level of transmittance greater than 50%, such as a level of transmittance greater than 50% at a wavelength from about 300 nm to about 900 nm. In some embodiments, the film has a level of transmittance between about 50% and 100% at a wavelength from about 300 nm to about 900 nm. In some embodiments of any one of the aspects, the film has a level of transmittance of about 55%, e.g., about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95% or higher at a wavelength from about 300 nm to about 900 nm. In some preferred embodiments, the film has a level of transmittance of about 90% or higher at a wavelength from about 300 nm to about 900 nm.

[0140] In some embodiment of any of the aspects, wherein the film has minimal fluorescent scattering. As used herein, “fluorescent scattering” describes the process where a material absorbs light at a certain wavelength and re-emits the light at a longer wavelength.

[0141] In some embodiments of any of the aspects, the film further comprises a therapeutic agent.

[0142] In some embodiments of any of the aspects, the film further comprises a therapeutic agent, and wherein the therapeutic agent is released from the film when the film undergoes a hydrophobic-to-hydrophilic transition.

[0143] In some embodiments of any of the aspects, the film further comprises a therapeutic agent, wherein the therapeutic agent is released from the film when the film is exposed to a reactive oxygen species.

[0144] In some embodiments of any of the aspects, the film further comprises a therapeutic agent, wherein the release of the therapeutic agent from the film is a controlled release.

[0145] As used herein, “controlled release” refers to a pharmaceutical composition or compound release profile that conforms to a particular pattern of release to effect a therapeutic outcome. As used herein, “sustained release” refers to a pharmaceutical composition or compound that conforms to a release rate over a specific period of time. The period of time may include, but is not limited to, hours, days, weeks, months and years.

[0146] In some embodiments of any of the aspects, the film further comprises a therapeutic agent, wherein the release of the therapeutic agent from the film is a sustained release.

[0147] In some embodiments of any of the aspects, the film is hydrophobic. For example, the film has a water contact angle of about 50 degrees or higher. For example, the water contact angle can be about 50 degrees, about 51 degrees, about 52 degrees, about 53 degrees, about 54 degrees, about 55 degrees, about 56 degrees, about 57 degrees, about 58 degrees, about 59 degrees,Attorney Docket No. 701586-000154WOPTabout 60 degrees, about 61 degrees, about 62 degrees, about 63 degrees, about 64 degrees, about 65 degrees, about 66 degrees, about 67 degrees, about 68 degrees, about 69 degrees, about 70 degrees, about 71 degrees, about 72 degrees, about 73 degrees, about 74 degrees, about 75 degrees, about 76 degrees, about 77 degrees, about 78 degrees, about 79 degrees, about 80 degrees, or higher than 80 degrees.

[0148] In some embodiments of any of the aspects, the fdm is hydrophilic. For example, the film has a water contact angle of about 40 degrees or lower. For example, the water contact angle can be about 40 degrees, about 39 degrees, about 38 degrees, about 37 degrees, about 36 degrees, about 35 degrees, about 34 degrees, about 33 degrees, about 32 degrees, about 31 degrees, about 30 degrees, about 29 degrees, about 28 degrees, about 27 degrees, about 26 degrees, about 25 degrees, about 24 degrees, about 23 degrees, about 22 degrees, about 21 degrees, about 20 degrees, about 19 degrees, about 18 degrees, about 17 degrees, about 16 degrees, about 15 degrees, or lower that 15 degrees.

[0149] In some embodiments of any of the aspects, the film is biocompatible. In some embodiments of any of the aspects, the film is non-biodegradable or non-resorbable. In some embodiments of any of the aspects, the film is biodegradable. In some embodiments of any of the aspects, the film is non-immunogenic. In some embodiments of any of the aspects, the film is antifouling.

[0150] It is noted that the film can be a single layer or can comprise multiple layers. Thus, in some embodiments of any of the aspects, the film comprises two or more layers to form a multilayered film. Each layer in the multilayer film can be the same or different. For example, the layers can be of the same thickness, each is of different thickness, or some are of same thickness and others are of different thickness. Further, each layer can be made from the same material, different materials or some from same materials and some from different materials.

[0151] In some embodiments of any of the aspects, the film comprises at least two layers, wherein a first layer comprises a first polymer described herein and a second layer comprises a second polymer that is different from the first polymer. It is noted that the second polymer can be a polymer described herein or a polymer known in the art.

[0152] In some embodiments of any of the aspects, the film is on a surface of a substrate. As used herein, “substrate” refers to any surface upon which a film or coating is applied to the surface of. In some embodiments of any of the aspects, the substrate is a medical device. As used herein, “medical device” refers to a device that is introduced temporarily or permanently into a subject for the prophylaxis or therapy of a medical condition. These devices include any that are introduced subcutaneously, percutaneously or surgically to rest within an organ, tissue or lumen. Medical devices may include stents, covered stents such as those covered withAttorney Docket No. 701586-000154WOPTpolytetrafluoroethylene (PTFE), or expanded polytetrafluoroethylene (ePTFE), synthetic grafts, artificial heart valves, artificial hearts and fixtures to connect the prosthetic organ to the vascular circulation, venous valves, abdominal aortic aneurysm (AAA) grafts, inferior venal caval filters, permanent drug infusion catheters, embolic coils, embolic materials used in vascular embolization (e.g., PVA foams), and vascular sutures.

[0153] In another aspect described herein is a fiber comprising a thioether-functionalized polymer described herein.

[0154] As used herein, “fiber” refers to a solid composition wherein the length of the material is larger than the width and height of the material.

[0155] In some embodiments of any of the aspects, the fiber has a diameter between about 1 nm and 5 mm. For example, the fiber has a diameter of from about 1 nm to about 5 nm, from about 1.1 nm to about 5 nm, from about 1.2 nm to about 5 nm, from about 1.3 nm to about 5 nm, from about 1.4 nm to about 5 nm, from about 1.5 nm to about 5 nm, from about 1.6 nm to about 5 nm, from about 1.7 nm to about 5 nm, from about 1.8 nm to about 5 nm, from about 1.9 nm to about 5 nm, from about 2 nm to about 5 nm, from about 2.1 nm to about 5 nm, from about 2.2 nm to about 5 nm, from about 2.3 nm to about 5 nm, from about 2.4 nm to about 5 nm, from about 2.5 nm to about 5 nm, from about 2.6 nm to about 5 nm, from about 2.7 nm to about 5 nm, from about 2.8 nm to about 5 nm, from about 2.9 nm to about 5 nm, from about 3 nm to about 5 nm, from about 3.1 nm to about 5 nm, from about 3.2 nm to about 5 nm, from about 3.3 nm to about 5 nm, from about 3.4 nm to about 5 nm, from about 3.5 nm to about 5 nm, from about 3.6 nm to about 5 nm, from about 3.7 nm to about 5 nm, from about 3.8 nm to about 5 nm, from about 3.9 nm to about 5 nm, from about 4 nm to about 5 nm, from about 4.1 nm to about 5 nm, from about 4.2 nm to about 5 nm, from about 4.3 nm to about 5 nm, from about 4.4 nm to about 5 nm, from about 4.5 nm to about 5 nm, from about 4.6 nm to about 5 nm, from about 4.7 nm to about 5 nm, from about 4.8 nm to about 5 nm, from about 4.9 nm to about 5 nm, from about 2 nm to about 4 nm, from about 2 nm to about 3.9 nm, from about 2 nm to about 3.8 nm, from about 2 nm to about 3.7 nm, from about 2 nm to about 3.6 nm, from about 2 nm to about 3.5 nm, from about 2 nm to about 3.4 nm, from about 2 nm to about 3.3 nm, from about 2 nm to about 3.2 nm, from about 2 nm to about 3.1 nm, from about 2 nm to about 3 nm, from about 2 nm to about 2.9 nm, from about 2 nm to about 2.8 nm, from about 2 nm to about 2.7 nm, from about 2 nm to about 2.6 nm, from about 2 nm to about 2.5 nm, from about 2 nm to about 2.4 nm, from about 2 nm to about 2.3 nm, from about 2 nm to about 2.2 nm, from about 2 nm to about 2.1 nm, from about 1 nm to about 4.9 nm, from about 1 nm to about 4.8 nm, from about 1 nm to about 4.7 nm, from about 1 nm to about 4.6 nm, from about 1 nm to about 4.5 nm, from about 1 nm to about 4.4 nm, from about 1 nm to about 4.3 nm, from about 1 nm to about 4.2 nm, from about 1 nm to about 4.1 nm, from about 1 nm toAttorney Docket No. 701586-000154WOPTabout 4 nm, from about 1 nm to about 3.9 nm, from about 1 nm to about 3.8 nm, from about 1 nm to about 3.7 nm, from about 1 nm to about 3.6 nm, from about 1 nm to about 3.5 nm, from about 1 nm to about 3.4 nm, from about 1 nm to about 3.3 nm, from about 1 nm to about 3.2 nm, from about 1 nm to about 3.1 nm, from about 1 nm to about 3 nm, from about 1 nm to about 2.9 nm, from about 1 nm to about 2.8 nm, from about 1 nm to about 2.7 nm, from about 1 nm to about 2.6 nm, from about 1 nm to about 2.5 nm, from about 1 nm to about 2.4 nm, from about 1 nm to about 2.3 nm, from about 1 nm to about 2.2 nm, from about 1 nm to about 2.1 nm, from about 1 nm to about 2 nm, from about 1 nm to about 1.9 nm, from about 1 nm to about 1.8 nm, from about 1 nm to about 1.7 nm, from about 1 nm to about 1.6 nm, from about 1 nm to about 1.5 nm, from about 1 nm to about 1.4 nm, from about 1 nm to about 1.3 nm, from about 1 nm to about 1.2 nm, or from about 1 nm to about 1.1 nm.

[0156] In some embodiments of any of the aspects, the fiber has a diameter of about 1.0 nm, about 1.1 nm, about 1.2 nm, about 1.3 nm, about 1.4 nm, about 1.5 nm, about 1.6 nm, about 1.7 nm, about 1.8 nm, about 1.9 nm, about 2.0 nm, about 2.1 nm, about 2.2 nm, about 2.3 nm, about 2.4 nm, about 2.5 nm, about 2.6 nm, about 2.7 nm, about 2.8 nm, about 2.9 nm, about 3.0 nm, about 3.1 nm, about 3.2 nm, about 3.3 nm, about 3.4 nm, about 3.5 nm, about 3.6 nm, about 3.7 nm, about 3.8 nm, about 3.9 nm, about 4.0 nm, about 4.1 nm, about 4.2 nm, about 4.3 nm, about 4.4 nm, about 4.5 nm, about 4.6 nm, about 4.7 nm, about 4.8 nm, about 4.9 nm, or about 5.0 nm.

[0157] Fiber diameter can be measured, for example, using Scanning Electron Microscopy or Transmission Electron Microscopy.

[0158] In yet another aspect provided herein is a particle comprising a thioether-functionalized cellulose polymer of any one of the embodiments.

[0005] As used herein, “particle” refers to a small, localized portion of matter. The particle size can range from about 1 nm to about 15 pm, e.g., about 1 nm to about 2 pm. Fror example, the particle size can be about 5nm, about 10 nm, about 15 nm, about 20 nm, 25 nm, about 50 nm, about 75 nm, about 100 nm, about 125 nm, about 150 nm, about 175 nm, about 200 nm, about 225 nm, about 250 nm, about 275 nm, about 300 nm, about 325 nm, about 350 nm, about 375 nm, about 400 nm, about 425 nm, about 450 nm, about 475 nm, about 500 nm, about 525 nm, about 550 nm, about 575 nm, about 600 nm, about 625 nm, about 650 nm, about 675 nm, about 700 nm, about 725 nm, about 750 nm, about 775 nm, about 800 nm, about 825 nm, about 850 nm, about 875 nm, about 900 nm, about 925 nm, about 950 nm, about 975 nm, about 1000 nm, about 125 nm, about 150 nm, about 175 nm, about 1100 nm, about 1125 nm, about 1150 nm, about 1175 nm, about 1200 nm, about 1225 nm, about 1250 nm, about 1275 nm, about 1300 nm, about 1325 nm, about 1350 nm, about 1375 nm, about 1400 nm, about 1425 nm, about 1450 nm, about 1475 nm, about 1500 nm, about 1525 nm, about 1550 nm, about 1575 nm, about 1600 nm, about 1625 nm, about 1650Attorney Docket No. 701586-000154WOPTnm, about 1675 nm, about 1700 nm, about 1725 nm, about 1750 nm, about 1775 nm, about 1800 nm, about 1825 nm, about 1850 nm, about 1875 nm, about 1900 nm, about 1925 nm, about 1950 nm, about 1975 nm, or about 2000 nm.

[0006] In some embodiments of any of the aspects, the particle has a diameter of between about 1 nm and about 2 microns. For example, the particle can have a diameter of between from about 0 nm to about 2 pm, from about 0 nm to about 1.9 pm, from about 0 nm to about 1.8 pm, from about 0 nm to about 1.7 pm, from about 0 nm to about 1.6 pm, from about 0 nm to about 1.5 pm, from about 0 nm to about 1.4 pm, from about 0 nm to about 1.3 pm, from about 0 nm to about 1.2 pm, from about 0 nm to about 1.1 pm, from about 0 nm to about 1.0 pm, from about 0 nm to about 900 nm, from about 0 nm to about 800 nm, from about 0 nm to about 700 nm, from about 0 nm to about 600 nm, from about 0 nm to about 500 nm, from about 0 nm to about 400 nm, from about 0 nm to about 300 nm, from about 0 nm to about 200 nm, from about 0 nm to about 100 nm, from about 100 nm to about 1.5 pm, from about 100 nm to about 1.45 pm, from about 100 nm to about 1.4 pm, from about 100 nm to about 1.35 pm, from about 100 nm to about 1.3 pm, from about 100 nm to about 1.25 pm, from about 100 nm to about 1.2 pm, from about 100 nm to about 1.15 pm, from about 100 nm to about 1.1 pm, from about 100 nm to about 1.05 pm, from about 100 nm to about 1 pm, from about 100 nm to about 950 nm, from about 100 nm to about 900 nm, from about 100 nm to about 850 nm, from about 100 nm to about 800 nm, from about 100 nm to about 750 nm, from about 100 nm to about 700 nm, from about 100 nm to about 650 nm, from about 100 nm to about 600 nm, from about 100 nm to about 550 nm, from about 100 nm to about 500 nm, from about 100 nm to about 450 nm, from about 100 nm to about 400 nm, from about 100 nm to about 350 nm, from about 100 nm to about 300 nm, from about 100 nm to about 250 nm, from about 100 nm to about 200 nm, from about 100 nm to about 150 nm, from about 1 nm to about 2 pm, from about 100 nm to about 2 pm, from about 200 nm to about 2 pm, from about 300 nm to about 2 pm, from about 400 nm to about 2 pm, from about 500 nm to about 2 pm, from about 600 nm to about 2 pm, from about 700 nm to about 2 pm, from about 800 nm to about 2 pm, from about 900 nm to about 2 pm, from about 1.0 pm to about 2 pm, from about 1.1 pm to about 2 pm, from about 1.2 pm to about 2 pm, from about 1.3 pm to about 2 pm, from about 1.4 pm to about 2 pm, from about 1.5 pm to about 2 pm, from about 1.6 pm to about 2 pm, from about 1.7 pm to about 2 pm, from about 1.8 pm to about 2 pm, or from about 1.9 pm to about 2 pm.

[0007] In some embodiments of any of the aspects, the particle has a diameter of about 1 nm, about 50 nm, about 100 nm, about 150 nm, about 200 nm, about 250 nm, about 300 nm, about 350 nm, about 400 nm, about 450 nm, about 500 nm, about 550 nm, about 600 nm, about 650 nm, about 700 nm, about 750 nm, about 800 nm, about 850 nm, about 900 nm, about 950 nm, about 1 pm, about 1.05 pm, about 1.1 pm, about 1.15 pm, about 1.2 pm, about 1.25 pm, about 1.3 pm, aboutAttorney Docket No. 701586-000154WOPT1.35 pm, about 1.4 jam, about 1.45 jam, about 1.5 jam, about 1.55 jam, about 1.6 jam, about 1.65 jam, about 1.7 jam, about 1.75 jam, about 1.8 jam, about 1.85 jam, about 1.9 jam, about 1.95 jam, or about 2 jam.

[0008] It will be understood by one of ordinary skill in the art that particles usually exhibit a distribution of particle sizes around the indicated “size.” Unless otherwise stated, the term “particle size” as used herein refers to the mode of a size distribution of particles, i.e., the value that occurs most frequently in the size distribution. Methods for measuring the particle size are known to a skilled artisan, e.g., by dynamic light scattering (such as photo-correlation spectroscopy, laser diffraction, low-angle laser light scattering (LALLS), and medium-angle laser light scattering (MALLS)), light obscuration methods (such as Coulter analysis method), or other techniques (such as rheology, and light or electron microscopy).

[0009] In some embodiments, the particles can be substantially spherical. What is meant by “substantially spherical” is that the ratio of the lengths of the longest to the shortest perpendicular axes of the particle cross section is less than or equal to about 1.5. Substantially spherical does not require a line of symmetry. Further, the particles can have surface texturing, such as lines or indentations or protuberances that are small in scale when compared to the overall size of the particle and still be substantially spherical. In some embodiments, the ratio of lengths between the longest and shortest axes of the particle is less than or equal to about 1.5, less than or equal to about 1.45, less than or equal to about 1.4, less than or equal to about 1.35, less than or equal to about 1.30, less than or equal to about 1.25, less than or equal to about 1.20, less than or equal to about 1.15 less than or equal to about 1.1. Without wishing to be bound by a theory, surface contact is minimized in particles that are substantially spherical, which minimizes the undesirable agglomeration of the particles upon storage. Many crystals or flakes have flat surfaces that can allow large surface contact areas where agglomeration can occur by ionic or non-ionic interactions. A sphere permits contact over a much smaller area.

[0010] In some embodiments, the particles have substantially the same particle size. Particles having a broad size distribution where there are both relatively big and small particles allow for the smaller particles to fdl in the gaps between the larger particles, thereby creating new contact surfaces. A broad size distribution can result in larger spheres by creating many contact opportunities for binding agglomeration. The particles described herein are within a narrow size distribution, thereby minimizing opportunities for contact agglomeration. What is meant by a “narrow size distribution” is a particle size distribution that has a ratio of the volume diameter of the 90th percentile of the small spherical particles to the volume diameter of the 10th percentile less than or equal to 5. In some embodiments, the volume diameter of the 90th percentile of the small spherical particles to the volume diameter of the 10th percentile is less than or equal to 4.5,Attorney Docket No. 701586-000154WOPTless than or equal to 4, less than or equal to 3.5, less than or equal to 3, less than or equal to 2.5, less than or equal to 2, less than or equal to 1.5, less than or equal to 1.45, less than or equal to 1.40, less than or equal to 1.35, less than or equal to 1.3, less than or equal to 1.25, less than or equal to 1.20, less than or equal to 1.15, or less than or equal to 1.1.

[0011] Geometric Standard Deviation (GSD) can also be used to indicate the narrow size distribution. GSD calculations involved determining the effective cutoff diameter (ECD) at the cumulative less than percentages of 15.9% and 84.1%. GSD is equal to the square root of the ratio of the ECD less than 84.17% to ECD less than 15.9%. The GSD has a narrow size distribution when GSD<2.5. In some embodiments, GSD is less than 2, less than 1.75, or less than 1.5. In one embodiment, GSD is less than 1.8.

[0159] In some embodiments of any of the aspects, the particle is a microparticle or a nanoparticle. As used herein, "nanoparticle" refers to any particle having at least one major dimension in the nanometer range. Typically, nanoparticles have at least one major dimension ranging from about 1 nm to about 1000 nm. As used herein, “microparticle” refers to any particle having at least one major dimension in the micrometer range. Typically, microparticles have at least one major dimension ranging from about 1 pm to about 10 pm.

[0160] In some embodiments of any of the aspects, the thioether-functionalized cellulose polymer is at a surface of the particle. For example, the particle comprises a core and a layer comprising a polymer descried herein and coating the core.

[0161] In some embodiments of any of the aspects, the thioether-functionalized cellulose polymer is in an interior of the particle. For example, the particle comprises a core comprising a polymer described herein and a coating layer on the core.

[0162] In some embodiments of any of the aspects, the particle further comprises a therapeutic agent. In some embodiments of any of the aspects, the therapeutic agent is released from the particle when the particle undergoes a hydrophobic-to-hydrophilic transition. In some embodiments of any of the aspects, therapeutic agent is released from the particle when the particle is exposed to a reactive oxygen species. In some embodiments of any of the aspects, the release of the therapeutic agent from the particle is a controlled release. In some embodiments of any of the aspects, the release of the therapeutic agent from the particle is a sustained release.

[0163] In still another aspect, provided herein is a substrate comprising a coating or fdm on at least a portion of a surface of the substrate, wherein the coating or film comprises a thioether-functionalized cellulose polymer described herein. In some embodiments of any of the aspects, the substrate is a medical device. In some embodiments of any of the aspects, the medical device is a catheter, a pacemaker, a drug infusion pump, an implanted optical system, a stent, a vascular graft,Attorney Docket No. 701586-000154WOPTa neurostimulator, a cochlear implant, an orthopedic implant, a cardiac lead, a biosensor, an artificial heart valve, an implantable glucose monitor, or an implantable drug depot.

[0164] In some embodiments of any of the aspects, the coating or film has a thickness from about 0.1 pm to about 150 pm. For example, the coating or film thickness can be from about 1 pm to about 150 pm, from about 1 pm to about 140 pm, from about 1 pm to about 130 pm, from about 1 pm to about 120 pm, from about 1 pm to about 110 pm, from about 1 pm to about 100 pm, from about 1 pm to about 90 pm, from about 1 pm to about 80 pm, from about 1 pm to about 70 pm, from about 1 pm to about 60 pm, from about 1 pm to about 50 pm, from about 1 pm to about 40 pm, from about 1 pm to about 30 pm, from about 1 pm to about 20 pm, from about 1 pm to about 10 pm, from about 10 pm to about 100 pm, from about 10 pm to about 95 pm, from about 10 pm to about 90 pm, from about 10 pm to about 85 pm, from about 10 pm to about 80 pm, from about 10 pm to about 75 pm, from about 10 pm to about 70 pm, from about 10 pm to about 65 pm, from about 10 pm to about 60 pm, from about 10 pm to about 55 pm, from about 10 pm to about 50 pm, from about 10 pm to about 45 pm, from about 10 pm to about 40 pm, from about 10 pm to about 35 pm, from about 10 pm to about 30 pm, from about 10 pm to about 25 pm, from about 10 pm to about 20 pm, from about 10 pm to about 15 pm, from about 50 pm to about 150 pm, from about 55 pm to about 150 pm, from about 60 pm to about 150 pm, from about 65 pm to about 150 pm, from about 70 pm to about 150 pm, from about 75 pm to about 150 pm, from about 80 pm to about 150 pm, from about 85 pm to about 150 pm, from about 90 pm to about 150 pm, from about 95 pm to about 150 pm, from about 100 pm to about 150 pm, from about 105 pm to about 150 pm, from about 110 pm to about 150 pm, from about 115 pm to about 150 pm, from about 120 pm to about 150 pm, from about 125 pm to about 150 pm, from about 130 pm to about 150 pm, from about 135 pm to about 150 pm, from about 140 pm to about 150 pm, or from about 145 pm to about 150 pm.

[0165] In some embodiments of any of the aspects, the coating or film has a thickness of about 1 pm, about 2.5 pm, about 5 pm, about 7.5 pm, about 10 pm, about 12.5 pm, about 15 pm, about 17.5 pm, about 20 pm, about 22.5 pm, about 25 pm, about 27.5 pm, about 30 pm, about 32.5 pm, about 35 pm, about 37.5 pm, about 40 pm, about 42.5 pm, about 45 pm, about 47.5 pm, about 50 pm, about 52.5 pm, about 55 pm, about 57.5 pm, about 60 pm, about 62.5 pm, about 65 pm, about 67.5 pm, about 70 pm, about 72.5 pm, about 75 pm, about 77.5 pm, about 80 pm, about 82.5 pm, about 85 pm, about 87.5 pm, about 90 pm, about 92.5 pm, about 95 pm, about 97.5 pm, about 100 pm, about 102.5 pm, about 105 pm, about 107.5 pm, about 110 pm, about 112.5 pm, about 115 pm, about 117.5 pm, about 120 pm, about 122.5 pm, about 125 pm, about 127.5 pm, about 130 pm, about 132.5 pm, about 135 pm, about 137.5 pm, about 140 pm, about 142.5 pm, about 145 pm, about 147.5 pm, or about 150 pm.Attorney Docket No. 701586-000154WOPT

[0166] In some embodiments of any of the aspects, the coating or film has a thickness from about 1 pm to about 75 pm. For example, the coating or film can have a thickness of about 1 pm, about 1.5 pm, about 2 pm, about 2.5 pm, about 3 pm, about 3.5 pm, about 4 pm, about 4.5 pm, about 5 pm, about 5.5 pm, about 6 pm, about 6.5 pm, about 7 pm, about 7.5 pm, about 8 pm, about 8.5 pm, about 9 pm, about 9.5 pm, about 10 pm, about 10.5 pm, about 11 pm, about 11.5 pm, about 12 pm, about 12.5 pm, about 13 pm, about 13.5 pm, about 14 pm, about 14.5 pm, about 15 pm, about 15.5 pm, about 16 pm, about 16.5 pm, about 17 pm, about 17.5 pm, about 18 pm, about 18.5 pm, about 19 pm, about 19.5 pm, about 20 pm, about 20.5 pm, about 21 pm, about 21.5 pm, about 22 pm, about 22.5 pm, about 23 pm, about 23.5 pm, about 24 pm, about 24.5 pm, about 25 pm, about 25.5 pm, about 26 pm, about 26.5 pm, about 27 pm, about 27.5 pm, about 28 pm, about 28.5 pm, about 29 pm, about 29.5 pm, about 30 pm, about 30.5 pm, about 31 pm, about 31.5 pm, about 32 pm, about 32.5 pm, about 33 pm, about 33.5 pm, about 34 pm, about 34.5 pm, about 35 pm, about 35.5 pm, about 36 pm, about 36.5 pm, about 37 pm, about 37.5 pm, about 38 pm, about 38.5 pm, about 39 pm, about 39.5 pm, about 40 pm, about 40.5 pm, about 41 pm, about 41.5 pm, about 42 pm, about 42.5 pm, about 43 pm, about 43.5 pm, about 44 pm, about 44.5 pm, about 45 pm, about 45.5 pm, about 46 pm, about 46.5 pm, about 47 pm, about 47.5 pm, about 48 pm, about 48.5 pm, about 49 pm, about 49.5 pm, about 50 pm, about 50.5 pm, about 51 pm, about 51.5 pm, about 52 pm, about 52.5 pm, about 53 pm, about 53.5 pm, about 54 pm, about 54.5 pm, about 55 pm, about 55.5 pm, about 56 pm, about 56.5 pm, about 57 pm, about 57.5 pm, about 58 pm, about 58.5 pm, about 59 pm, about 59.5 pm, about 60 pm, about 60.5 pm, about 61 pm, about 61.5 pm, about 62 pm, about 62.5 pm, about 63 pm, about 63.5 pm, about 64 pm, about 64.5 pm, about 65 pm, about 65.5 pm, about 66 pm, about 66.5 pm, about 67 pm, about 67.5 pm, about 68 pm, about 68.5 pm, about 69 pm, about 69.5 pm, about 70 pm, about 70.5 pm, about 71 pm, about 71.5 pm, about 72 pm, about 72.5 pm, about 73 pm, about 73.5 pm, about 74 pm, about 74.5 pm, or about 75 pm.

[0167] The coating can have an average surface roughness (Ra), as measured on a 5 pm *5 pm area, within a range having a lower limit and / or an upper limit. The range can include or exclude the lower limit and / or the upper limit. The lower limit and / or upper limit can be selected from about 5 nm, about 10 nm, about 15, about 20 nm, about 25 nm, about 30 nm, about 35 nm, about 40 nm, about 45 nm, about 50 nm, about 55 nm, about 60 nm, about 65 nm, about 70 nm, about 75 nm, about 80, about 85 nm, about 90 nm, about 95 nm, about 100 nm, about 105 nm, about 110 nm, about 115 nm, about 120 nm, about 125 nm, about 130 nm, about 135 nm, about 140 nm, about 145 nm, about 150 nm, about 155 nm, about 160 nm, about 165 nm, about 170 nm, about 175 nm, about 180 nm, about 185 nm, about 190 nm, about 195 nm, about 200 nm, about 205 nm, about 210 nm, about 215 nm, about 220 nm, about 225 nm, about 230 nm, about 235 nm, about 240 nm,Attorney Docket No. 701586-000154WOPTabout 245 nm, and about 250 nm. For example, according to some embodiments, the coating has an average surface roughness (Ra) of from about 5 nm to about 50 nm, as measured on a 5 pm x 5 pm area. In some embodiments, the coating can have an average surface roughness of from about 50 nm to about 100 nm, from about 105 nm to about 200 nm, or from about 200 nm to about 250 nm.

[0168] In some embodiments of any of the aspects, the coating or fdm has an average surface roughness from about 5 nm to about 50 nm. For example, the film has an average surface roughness of about 5 nm, about 6 nm, about 7 nm, about 8 nm, about 9 nm, about 10 nm, about 11 nm, about 12 nm, about 13 nm, about 14 nm, about 15 nm, about 16 nm, about 17 nm, about 18 nm, about 19 nm, about 20 nm, about 21 nm, about 22 nm, about 23 nm, about 24 nm, about 25 nm, about 26 nm, about 27 nm, about 28 nm, about 29 nm, about 30 nm, about 31 nm, about 32 nm, about 33 nm, about 34 nm, about 35 nm, about 36 nm, about 37 nm, about 38 nm, about 39 nm, about 40 nm, about 41 nm, about 42 nm, about 43 nm, about 44 nm, about 45 nm, about 46 nm, about 47 nm, about 48 nm, about 49 nm, or about 50 nm.

[0169] In some embodiments of any of the aspects, the coating or film comprises a therapeutic agent.

[0170] In some embodiments of any of the aspects, the coating or film is hydrophobic. For example, the coating or film has a water contact angle of about 50 degrees or higher. For example, the water contact angle can be about 50 degrees, about 51 degrees, about 52 degrees, about 53 degrees, about 54 degrees, about 55 degrees, about 56 degrees, about 57 degrees, about 58 degrees, about 59 degrees, about 60 degrees, about 61 degrees, about 62 degrees, about 63 degrees, about 64 degrees, about 65 degrees, about 66 degrees, about 67 degrees, about 68 degrees, about 69 degrees, about 70 degrees, about 71 degrees, about 72 degrees, about 73 degrees, about 74 degrees, about 75 degrees, about 76 degrees, about 77 degrees, about 78 degrees, about 79 degrees, about 80 degrees, or higher than 80 degrees.

[0171] In some embodiments of any of the aspects, the coating or film is hydrophilic. For example, the film has a water contact angle of about 40 degrees or lower. For example, the water contact angle can be about 40 degrees, about 39 degrees, about 38 degrees, about 37 degrees, about 36 degrees, about 35 degrees, about 34 degrees, about 33 degrees, about 32 degrees, about 31 degrees, about 30 degrees, about 29 degrees, about 28 degrees, about 27 degrees, about 26 degrees, about 25 degrees, about 24 degrees, about 23 degrees, about 22 degrees, about 21 degrees, about 20 degrees, about 19 degrees, about 18 degrees, about 17 degrees, about 16 degrees, about 15 degrees, or lower that 15 degrees.

[0172] In some embodiments of any of the aspects, the coating or film is biocompatible. In some embodiments of any of the aspects, the coating or film is non-biodegradable or nonAttorney Docket No. 701586-000154WOPTresorbable. In some embodiments of any of the aspects, wherein the coating or film is non-immunogenic. In some embodiments of any of the aspects, the coating or film is antifouling.

[0173] In some embodiments, the coating is multilayer coating. For example, the coating can comprise two or more layers. Each layer in the multilayer structure can be the same or different. For example, the layers can be of the same thickness, each is of different thickness, or some are of same thickness and others are of different thickness. Further, each layer can be made from the same material, different materials or some from same materials and some from different materials.

[0174] One aspect of the technology disclosed herein is a drug-delivery article comprising a thioether-functionalized cellulose polymer of any one of the embodiments and a therapeutic agent. As used herein, “drug-delivery article” refers to a vehicle for delivering a pharmacological agent to a subject.

[0175] In some embodiments of any of the aspects, the drug delivery article is in the form of a fdm, a particle, a mesh, a fiber, a gel, a hydrogel, a foam, a mesh, a mat, a non-woven mat, or any combinations thereof.

[0176] In some embodiments of any of the aspects, the drug delivery article is multilayered.

[0177] In some embodiments of any of the aspects, the drug delivery article comprises a coating or film on a surface of substrate, and wherein the coating or film comprises the thioether-functionalized cellulose polymer.

[0178] In some embodiments of any of the aspects, the thioether-functionalized cellulose polymer and the therapeutic agent are in a mixture, e.g., homogenous mixture.

[0179] As used herein, “mixture” refers to a physical combination of two or more substances that are not chemically bonded. A mixture can be homogenous, meaning having uniform composition throughout, or heterogenous, meaning it does not have a uniform composition

[0180] In some embodiments of any of the aspects, the thioether-functionalized cellulose polymer and the therapeutic agent are present separately in the drug delivery article.

[0181] In some embodiments of any of the aspects, the drug-delivery device is cylindrical, circular or spherical, rectangular, cubic, polyhedron, prism, disc, other geometric shape, or any combinations thereof.

[0182] In some embodiments of any of the aspects, drug delivery article is in form of an implant or an implantable device.

[0183] As used herein “implant” or “implantable device” refers to an article that is fully or partially placed in a subject, e.g., by surgery.

[0184] In yest still another aspect, provided herein is a method for controlling the release of a therapeutic agent. The method comprises: (a) providing a drug-delivery article or a film,Attorney Docket No. 701586-000154WOPTcoating, particle or fiber comprising a therapeutic agent described herein,; and (b) inducing a hydrophobic-to-hydrophilic transition in the thioether functionalized cellulose polymer.

[0185] Also provided herein is a method of forming a coating on a surface of a substrate. The method comprising applying a thioether-functionalized cellulose polymer described herein to at least a portion of a surface of the substrate.

[0186] A surface can be coated by any suitable technique known in the art. Exemplary coating methods include, but are not limited to, spin coating, nozzle-assisted printing (e.g., inkjet printing), drop-casting, blade coating, 3D printing, zone-casting, roll coating, roll-to-roll (R2R) coating, spray coating, dip coating, die coating, slot die coating, roll coating, comma coating gravure coating, bar coating, vapor coating, knife coating, or combinations thereof.

[0187] In some embodiments, the surface is coated by spin-coating. Spin coating is a surface coating method in which the coating material, e.g., a composition described herein is deposited on the surface to be coated. The surface is attached to a spinner, which causes the spinner to rotate the surface at a controlled speed, thereby spreading the coating material onto the surface and wetting the surface entirely with the coating material. Generally, the surface to be coated is spun at from about 250 rpm to about 5000 rpm. For example, the surface to be coated is spun at from about 500 rpm to about 4000 rpm, from about 1000 rpm to about 3000 rpm, from about 750 rpm to about 2500 rpm or from about 1000 rpm to about 2000 rpm. Inventors have discovered inter alia spinning the surface at about 1500 rpm unexpectedly provides a highly uniform coating layer. Accordingly, in some embodiments of any one of the aspects described herein, the surface to be coated is spun at from about 1250 rpm to about 1750 rpm. In some preferred embodiments, the surface to be coated is spun at about 1500 rpm

[0188] In some embodiments of any one of the aspects described herein, the surface is coated by nozzle-assisted printing (e.g., inkjet printing). Nozzle-assisted printing is a surface coating method in which ink jet technology is used to deposit coating materials on surfaces. Generally, the coating material is injected under pressure (e.g., from about 5 kPa to about 20 kPa). The printing speed can be adjusted as needed to make a uniform coating layer on the surface. For example, the printing speed can be from about 5 mm / s to about 20 mm / s. The temperature of printer bed can be an elevated temperature, e.g., a temperature of about 37°C or higher. In some embodiments, the temperature of the printer bed can be from about 37°C to about 70°C, from about 40°C to about 60°C, or from about 45°C to about 55°C. In some embodiments, the temperature of the printer bed is about 50°C.

[0189] In some embodiments of any one of the aspects described herein, the surface is coated by dip coating. Dip coating is a surface coating method in which the surface to be treated is immersed and then withdrawn from the coating material, e.g., a composition described herein atAttorney Docket No. 701586-000154WOPTa defined rate. The dip coating process can be, generally, separated into 3 stages: (i) immersion: the surface is immersed in the solution of the coating material at a constant speed; (ii) dwell time: the surface remains fully immersed and motionless to allow for the coating material to apply itself to the surface; and (lii) withdrawal: the surface is withdrawn, again at a constant speed. Without wishing to be bound by a theory, the faster the substrate is withdrawn the thicker the coating material that will be applied to the surface In some embodiments, dip coating comprises at least two or more rounds of immersion, dwell time, and withdrawal.

[0190] As used herein, “drop casting” refers to a method for creating a thin film by depositing a drop of liquid onto a surface and allowing the solvent to evaporate. As used herein “roll coating” refers to a process of applying a thin film or layer to a substrate by passing the substrate between applicator rollers, wherein the rollers are in contact with a liquid solution for transfer to the substrate.

[0191] In some embodiments of any of the aspects, the substrate is a medical device.

[0192] In some embodiments of any of the aspects, the polymer is applied as a solution.

[0193] In some embodiments of any of the aspects, the method further comprises a step of removing a solvent from the solution comprising the polymer after forming the coating or film.

[0194] In some embodiments of any of the aspects, the method comprises applying a solution comprising the polymer to a mold and removing a solvent from the solution after applying to the mold.

[0195] In some embodiments of any of the aspects, the step of removing the solvent comprises temperature and / or pressure-controlled vaporization of the solvent.

[0196] In some embodiments of any of the aspects, the method further comprises a step of drying the substrate after the step of applying the polymer.

[0197] In some embodiments of any of the aspects said drying step is under vacuum.

[0198] In some embodiments of any of the aspects, said drying step is at a temperature higher than room temperature.

[0199] In some embodiments, composition used for coating the surface comprises a therapeutic agent.

[0200] In still yet another aspect, provided herein is a method for preparing a thioether-functionalized cellulose polymer. The method comprises reacting a cellulose polymer with a thioether-functionalizing reagent.

[0201] As used herein, “thioether-functionalizing reagent” refers to a chemical capable of converting a hydroxyl group to a thioether group. Examples include, but are not limited to, isothiocyanate-based thioether-functionalizing reagents, e.g. 3-(methylthio)propyl isothiocyanate.Attorney Docket No. 701586-000154WOPT

[0202] In some embodiments of any of the aspects, thioether-functionalizing reagent is an isothiocyanate-based thioether-functionalizing reagent.

[0203] In some embodiments of any of the aspects, the thioether-functionalizing reagent is 3 -(methylthio)propyl isothiocyanate.

[0204] In some embodiments of any of the aspects, the polymer is hydroxyethyl cellulose (HEC) or methyl cellulose (MC) or Hydroxy propyl methylcellulose (HPMC).

[0205] In some embodiments of any of the aspects, the polymer is hydroxyethyl cellulose.

[0206] In some embodiments of any of the aspects, the cellulose polymer is hydroxyethyl cellulose.

[0207] In some embodiments of any of the aspects, the thioether-functionalized cellulose polymer is a polymer of any one of the embodiments described herein.

[0208] Some aspects of any of the embodiments are a polymeric mesh, foam, or hydrogel comprising a thioether-functionalized cellulose polymer of any one of the embodiments described herein.

[0209] Embodiments of the various aspects described herein include a therapeutic agent. As used herein, the term “therapeutic agent” refers to any biologically, physiologically or pharmacologically active substance that acts locally or systemically in or / and on a subject and is administered to a subject for purposes of diagnosis, treatment, mitigation, cure or prevention of a medical condition or enhancement of a desired physical or mental development or condition.

[0210] Exemplary therapeutic agents include, but are not limited to, antiplatelets, antithrombins, anti-adhesion agents, cytostatic agents, antiproliferative agents, vasodilators, alkylating agents, antimicrobials, antibiotics, antimitotics, anti -infective agents, antisecretory agents, anti-inflammatory agents, immunosuppressive agents, antimetabolite agents, growth factor antagonists, free radical scavengers, antioxidants, radiotherapeutic agents, anesthetic agents, radiopaque agents, radiolabeled agents, nucleotides, cells, proteins, glycoproteins, hormones, protein receptor agonists or antagonists, anti-stenosis agents, isolates, enzymes, monoclonal antibodies, ribonucleases, nutraceutical agents (e.g. vitamins, minerals, etc.), labeling agents (e.g., contrast agents, radionuclides, fluorescent agents, luminescent agents, magnetic agents), and any combinations thereof. Further, other vasoreactive agents such as nitric oxide releasing agents could also be used.

[0211] Exemplary antiplatelets include, e.g., irreversible cyclooxygenase inhibitors, Aspirin, Adenosine diphosphate (ADP) receptor inhibitors, Clopidogrel (Plavix), Prasugrel (Effient), Ticagrelor (Brilinta), Elinogrel, Ticlopidine (Ticlid), Phosphodiesterase inhibitors, Cilostazol (Pletal), Glycoprotein IIB / IIIA inhibitors (intravenous use only), Abciximab (ReoPro), Eptifibatide (Integrilin), Tirofiban (Aggrastat), Adenosine reuptake inhibitors, PAR-1 or PAR-4Attorney Docket No. 701586-000154WOPTantagonists, GPVI antagonists, Dipyridamole (Persantine), Thromboxane inhibitors, Thromboxane synthase inhibitors, Thromboxane receptor antagonists, Terutroban, and mixtures thereof.

[0212] Exemplary antithrombins include, e.g., heparin, aspirin, hirudin, dabigatran, Enoxaparin, anti-Xa, anti-XIIa, anti-IXa agents, GPIIb / IIIa receptor inhibitor as tirofiban, eptifibatide, cilostazol, plavix, Ticlid, urokinase, and PPack (dextrophenylalanine proline arginine chloromethylketone. Suitable anti-cancer agents include methotrexate, purine, pyridine, and botanical (e.g. paclitaxel, colchicines and triptolide), epothilone, antibiotics, and antibodies.

[0213] Anti-adhesion agents can include any agent that blocks and / or inhibits an adhesion molecule such as, e.g., cell adhesion molecules (CAM), intercellular adhesion molecules (ICAM), vascular cell adhesion molecules (VCAM), and others. Agents that block such adhesion molecules can include, e.g., antibodies, RNAi agents. Exemplary anti-adhesion agents include, by way of example only, ocriplasmin.

[0214] Cytostatic agents (e.g., alkylating agents and other agents) are described herein. Exemplary vasodilators include, e.g., Hydralazine, Minoxidil. Exemplary antimicrobials include, e.g., chlorhexidine diacetate, silver carbonate, and antimicrobial peptides (AMPs).

[0215] Exemplary anti-inflammatory agents include, e.g., steroids, non-steroidal antiinflammatory drugs (NSAIDs), and Immune Selective Anti-Inflammatory Derivatives (ImSAIDs). Exemplary steroids include glucocorticoids and corticosteroids, such as, e.g., hydrocortisone, hydrocortisone acetate, cortisone acetate, tixocortol pivalate, prednisolone, methylprednisolone, and prednisone, meprednisone, triamcinolone, paramethasone, fluprednisolone, betamethasone, dexamethasone, fludrocortisone, desoxycorticosterone, Triamcinolone acetonide, triamcinolone alcohol, mometasone, amcinonide, budesonide, desonide, fluocinonide, fluocinolone acetonide, and halcinonide, betamethasone, betamethasone sodium phosphate, dexamethasone sodium phosphate, and fluocortolone, Hydrocortisone- 17-val erate, halometasone, alclometasone dipropionate, betamethasone valerate, betamethasone dipropionate, prednicarbate, clobetasone-17-butyrate, clobetasol-17-propionate, fluocortolone caproate, fluocortolone pivalate, and fluprednidene acetate, Hydrocortisone- 17-butyrate, hydrocortisone- 17-aceponate, hydrocortisone- 17-buteprate, and prednicarbate. Exemplary NSAIDs include, e.g., Aspirin (acetylsalicylic acid), Diflunisal, Salsalate, Ibuprofen, Dexibuprofen, Naproxen, Fenoprofen, Ketoprofen, Dexketoprofen, Flurbiprofen, Oxaprozin, Loxoprofen, Indomethacin, Tolmetin, Sulindac, Etodolac, Ketorolac, Diclofenac, Nabumetone, Piroxicam, Meloxicam, Tenoxicam, Droxicam, Lomoxicam, Isoxicam, Mefenamic acid, Meclofenamic acid, Flufenamic acid, Tolfenamic acid, Celecoxib, Rofecoxib, Valdecoxib, Parecoxib, Lumiracoxib, Etoricoxib, Firocoxib, Paracetamol, Nimesulide, Licofelone acts, H-harpagide, Lysine clonixinate, and mixtures thereof. Exemplary ImSAIDs include, e.g., submandibular gland peptide-T, tripeptideAttorney Docket No. 701586-000154WOPTFEG (Phe-Glu-Gly) and its D-isomer feG. Illustrative anti-inflammatory agents also include COX-2 inhibitors, such as nimesulide, NS-398, flosulid, L-745337, celecoxib, rofecoxib, SC-57666, DuP-697, parecoxib sodium, JTE-522, valdecoxib, SC-58125, etoricoxib, RS-57067, L-748780, L-761066, APHS, etodolac, meloxicam, S-2474, and mixtures thereof; glucocorticoids, such as and mixtures thereof; the anti-inflammatory agent rapamycin; and mixtures thereof.

[0216] Exemplary immunosuppressive agents include, e.g., Azathioprine, cyclosporine, interferon, opioids, TNF-binding proteins, infliximab (Remicade), etanercept (Enbrel), or adalimumab, Mycophenolic acid, Fingolimod, Myriocin.

[0217] Anti-infective agents include, e.g., pyrimidine analogs. A “pyrimidine analog”, as used herein, generally refers to a compound with a pyrimidine ring structure (1,3-diazine) substituted with one or more atoms or chemical groups or oxidized at one or more carbons in the pyrimidine ring structure.

[0218] In some embodiments, the therapeutic agent can be an antibiotic. As used herein, the term “antibiotic” is art recognized and includes antimicrobial agents naturally produced by microorganisms such as bacteria (including Bacillus species), actinomycetes (including Streptomyces) or fungi that inhibit growth of or destroy other microbes, or genetically engineered thereof and isolated from such natural source. Substances of similar structure and mode of action can be synthesized chemically, or natural compounds can be modified to produce semi-synthetic antibiotics. Exemplary classes of antibiotics include, but are not limited to, (1) -lactams, including the penicillins, cephalosporins monobactams, methicillin, and carbapenems; (2) aminoglycosides, e.g., gentamicin, kanamycin, neomycin, tobramycin, netilmycin, paromomycin, and amikacin; (3) tetracyclines, e.g., doxycycline, minocycline, oxytetracycline, tetracycline, and demeclocy cline; (4) sulfonamides (e.g., mafenide, sulfacetamide, sulfadiazine and sulfasalazine) and trimethoprim; (5) quinolones, e.g., ciprofloxacin, norfloxacin, and ofloxacin; (6) glycopeptides (e.g., vancomycin, telavancin, teicoplanin); (7) macrolides, which include for example, erythromycin, azithromycin, and clarithromycin; (8) carbapenems (e.g., ertapenem, doripenem, meropenem, and imipenem); (9) cephalosporins (e.g., cefadroxil, ceftriaxone, cefepime, and ceftobiprole); (10) lincosamides (e.g., clindamycin, and lincomycin); (11) monobactams (e.g., aztreonam); (12) nitrofurans (e.g, furazolidone, and nitrofurantoin); (13) Penicillins (e.g., amoxicillin, and Penicillin G); (14) polypeptides (e.g., bacitracin, colistin, and polymyxin B); and (15) other antibiotics, e.g., ansamycins, polymycins, carbacephem, chloramphenicol, lipopeptide, and drugs against mycobacteria (e.g., the ones causing diseases in mammals, including tuberculosis (Mycobacterium tuberculosis) and leprosy (Mycobacterium leprae), and any combinations thereof. Additional exemplary antimicrobial agent can include, but are not limited to, antibacterial agents, antifungal agents, antiprotozoal agents, antiviral agents, and any mixtures thereof.Attorney Docket No. 701586-000154WOPT

[0219] In some embodiments of any one of the aspects described herein, the therapeutic agent is an anti-bacterial agent. Exemplary antibacterial agents include, but are not limited to, Acrosoxacin, Amifioxacin, Amoxycillin, Ampicillin, Aspoxicillin, Azidocillin, Azithromycin, Aztreonam, Balofloxacin, Benzylpenicillin, Biapenem, Brodimoprim, Cefaclor, Cefadroxil, Cefatrizine, Cefcapene, Cefdinir, Cefetamet, Cefmetazole, Cefprozil, Cefroxadine, Ceftibuten, Cefuroxime, Cephalexin, Cephalonium, Cephaloridine, Cephamandole, Cephazolin, Cephradine, Chlorquinaldol, Chlortetracycline, Ciclacillin, Cinoxacin, Ciprofloxacin, Clarithromycin, Clavulanic Acid, Clindamycin, Clofazimine, Cioxacillin, Danofloxacin, Dapsone, Demeclocycline, Dicloxacillin, Difloxacin, Doxycycline, Enoxacin, Enrofloxacin, Erythromycin, Fleroxacin, Flomoxef, Flucloxacillin, Flumequine, Fosfomycin, Isoniazid, Levofloxacin, Mandelic Acid, Mecillinam, Metronidazole, Minocycline, Mupirocin, Nadifloxacin, Nalidixic Acid, Nifuirtoinol, Nitrofurantoin, Nitroxoline, Norfloxacin, Ofloxacin, Oxytetracycline, Panipenem, Pefloxacin, Phenoxymethylpenicillin, Pipemidic Acid, Piromidic Acid, Pivampicillin, Pivmecillinam, Prulifloxacin, Rufloxacin, Sparfloxacin, Sulbactam, Sulfabenzamide, Sulfacytine, Sulfametopyrazine, Sulphacetamide, Sulphadiazine, Sulphadimidine, Sulphamethizole, Sulphamethoxazole, Sulphanilamide, Sulphasomidine, Sulphathiazole, Temafioxacin, Tetracycline, Tetroxoprim, Tinidazole, Tosufloxacin, Trimethoprim, and phramceutically acceptable salts or esters thereof.

[0220] In some embodiments of any one of the aspects described herein, the therapeutic agent is selected from the group consisting of macrolides or ketolides such as erythromycin, azithromycin, clarithromycin, and telithromycin; beta-lactams including penicillin, cephalosporin, and carbapenems such as carbapenem, imipenem, and meropenem; monolactams such as penicillin G, penicillin V, methicillin, oxacillin, cloxacillin, dicloxacillin, nafcillin, ampicillin, amoxicillin, carbenicillin, ticarcillin, meziocillin, piperacillin, azlocillin, temocillin, cepalothin, cephapirin, cephradine, cephaloridine, cefazolin, cefamandole, cefuroxime, cephalexin, cefprozil, cefaclor, loracarbef, cefoxitin, cefmetazole, cefotaxime, ceftizoxime, cefiriaxone, cefoperazone, ceftazidime, cefixime, cefpodoxime, ceftibuten, cefdinir, cefpirome, cefepime, cefadroxil, ceftriaxone, ceftobiprole and astreonam; quinolones such as nalidixic acid, oxolinic acid, norfloxacin, pefloxacin, enoxacin, ofloxacin, levofloxacin, ciprofloxacin, temafioxacin, lomefloxacin, fleroxacin, grepafloxacin, sparfloxacin, trovafloxacin, clinafloxacin, gatifloxacin, moxifloxacin, sitafloxacin, ganefloxacin, gemifloxacin and pazufloxacin; antibacterial sulfonamides and antibacterial sulphanilamides, including para-aminobenzoic acid, sulfadiazine, sulfisoxazole, sulfamethoxazole and sulfathalidine; aminoglycosides such as streptomycin, neomvcin, kanamycin, paromycin, gentamicin, tobramycin, amikacin, netilmicin, spectinomycin, sisomicin, dibekalin and isepamicin; tetracyclines such as tetracycline, chlortetracycline,Attorney Docket No. 701586-000154WOPTdemeclocycline, minocycline, oxytetracycline, methacycline, doxycycline; rifamycins such as rifampicin (also called rifampin), rifapentine, rifabutin, bezoxazinorifamycin and rifaximin; lincosamides such as lincomycin and clindamycin; glycopeptides such as vancomycin and teicoplanin; streptogramins such as quinupristin and daflopristin; oxazolidinones such as linezolid; polymyxin, colistin and colymycin; trimethoprim, bacitracin, and phosphonomycin. In some preferred embodiments, the therapeutic agent is gentamicin, ampicillin, vancomycin, ceftriaxone or cefepime.

[0221] In some embodiments of any one of the aspects described herein, the therapeutic is an antifungal agent. Exemplary antifungal agents include, but are not limited to, Bifonazole, Butoconazole, Chlordantoin, Chlorphenesin, Ciclopirox Olamine, Clotrimazole, Eberconazole, Econazole, Fluconazole, Flutrimazole, Isoconazole, Itraconazole, Ketoconazole, Miconazole, Nifuroxime, Tioconazole, Terconazole, Undecenoic Acid, and pharmaceutically acceptable salts or esters thereof. In some embodiments of any one of the aspects described herien, the antifungal agent is selected from the group consisting of azoles (e.g., barleyconazole, butoconazole, clortrimazole, econazole, fluconazole, isavuconazole, itraconazole, ketoconazole, miconazole, oxyconazole, posaconazole, ravuconazole, saperconazole, sulconazole, tercocnazole, tioconazole, voriconazole, and ciclopirox), polyenes (e.g., natamycin, lucensomycin, nystatin, amphotericin B, etc.), echinocandins (e.g., Cancidas), pradimicins (e.g., beanomicins, nikkomycins, sordarins, allylamines, etc.), Triclosan, Piroctone, fenpropimorph, terbinafine, cyclopyroxolamine, flucitocin, griseofulvin haloprozin, tolnaftate, naphthypine, hydrochloride, morpholine, butenapin, undecylenic acid, propionic acid, and derivatives and analogs thereof.

[0222] In some embodiments of any one of the aspects described herein, the therapeutic agent is an antiprotozoal agent. Exemplary antiprotozoal agents include, but are not limited to, Acetarsol, Azanidazole, Chloroquine, Metronidazole, Nifuratel, Nimorazole, Omidazole, Propenidazole, Secnidazole, Sineflngin, Tenonitrozole, Temidazole, Tinidazole, and pharmaceutically acceptable salts or esters thereof.

[0223] In some embodiments of any one of the aspects described herein, the therapeutic agent is an antiviral agent. Exemplary antiviral agents include, but are not limited to, Acyclovir, Brivudine, Cidofovir, Curcumin, Desciclovir, 1 -Docosanol, Edoxudine, Fameyclovir, Fiacitabine, Ibacitabine, Imiquimod, Lamivudine, Penciclovir, Valacyclovir, Valganciclovir, and pharmaceutically acceptable salts or esters thereof.

[0224] A therapeutic agent can be, for example, but not limited to, a small molecule, a peptide, a peptidomimetics, an antibody or a fragment thereof, a nucleic acid, an enzyme (e.g., an antimicrobial metalloendopeptidase such as lysostaphin), an aptamer, a drug, an antibiotic, a chemical or any entity that can inhibit the growth and / or kill a microbe. In some embodiments ofAttorney Docket No. 701586-000154WOPTany one of the aspects described herein, the therapeutic agent is an antimicrobial peptide or polymer. Examples of antimicrobial peptides include, but are not limited to, mefloquine, venturicidin A, antimycin, myxothiazol, stigmatellin, diuron, iodoacetamide, potassium tellurite hydrate, aDL-vinylglycine, N-ethylmaleimide, L-allyglycine, diaryquinoline, betaine aldehyde chloride, acivcin, psicofuraine, buthionine sulfoximine, diaminopemelic acid, 4-phospho-D-erythronhydroxamic acid, motexafin gadolinium, xycitrin, catheli cidins, defensins, protegrins, mastoparan, poneratoxin, cecropin, moricin, melittin, magainin, dermaseptin, and / or nisin, or modified versions or analogues thereof.

[0225] In some embodiments, the therapeutic agent is anti-microbial agent which is a metal particle. Exemplary metal particles can include silver, titanium oxide, or copper present in any form, e.g., a nanoparticle, a colloid, a suspension, powder, and any combinations thereof. In some embodiments of any one of the aspects described herein the anti-microbial agent is titanium oxide, copper, or silver nanoparticles.

[0226] In some embodiments, the present technology may be defined in any of the following numbered embodiments:

[0227] Embodiment 1: A thioether-functionalized cellulose polymer, comprising a cellulose backbone of repeating anhydroglucose units and thioether substituents covalently attached to at least a portion of the hydroxyl groups of said repeating anhydroglucose units.

[0228] Embodiment 2: The polymer of embodiment 1, wherein the polymer is hydroxyethyl cellulose (HEC) or methyl cellulose (MC) or Hydroxy propyl methylcellulose (HPMC).

[0229] Embodiment 3: The polymer of any one of embodiments 1-2, wherein the polymer is hydroxyethyl cellulose.

[0230] Embodiment 4: The polymer of any one of embodiments 1-3, wherein the polymer is oxidation-responsive.

[0231] Embodiment 5: The polymer of any one of embodiments 1-4, wherein the polymer undergoes a hydrophobic-to-hydrophilic transition upon exposure to a reactive oxygen species (ROS).

[0232] Embodiment 6: The polymer of any one of embodiments 1-5, wherein at least a portion of the thioether substituents are oxidized to sulfoxide or sulfone.

[0233] Embodiment 7: The polymer of any one of embodiments 1-6, wherein at least a portion of the thioether substituents are alkylated to sulfonium ions.

[0234] Embodiment 8: The polymer of any of embodiments 1-7, wherein at least a portion of the thioether substituents are zwitterionic.Attorney Docket No. 701586-000154WOPT

[0235] Embodiment 9: The polymer of any one of embodiments 1-8, wherein at least 2.5 mol % of the hydroxyl groups in the polymer are modified with the thioether substituent.

[0236] Embodiment 10: The polymer of any one of embodiments 1-9, wherein from about 2.5 to about 95 mol% of the hydroxyl groups in the polymer are modified with the thioether substituent.

[0237] Embodiment 11: The polymer of any one of embodiments 1-10, wherein 5-30 mol% of the hydroxyl groups in the polymer are modified with the thioether substituent.

[0238] Embodiment 12: The polymer of any one of embodiments 1-11, wherein the polymer comprises an average of about 0.5 to 2 thioether groups per anhydroglucose repeat unit.

[0239] Embodiment 13: The polymer of any one of embodiments 1-12, wherein each anhydroglucose repeat unit comprises about 0.63 thioether groups.

[0240] Embodiment 14: The polymer of any one of embodiments 1-13, wherein the polymer comprises from about 10 to about 100,000 anhydroglucose repeat units.

[0241] Embodiment 15: The polymer of any one of embodiments 1-14, wherein the polymer has a molecular weight (MW) of from about 0.5kDa to about 1,000 kDa.

[0242] Embodiment 16: The polymer of any one of embodiments 1-15, wherein the polymer has a molecular weight (MW) of from about 300 kDa to about 500 kDa.

[0243] Embodiment 17: The polymer of any one of embodiments 1-16, wherein the polymer has a polymer dispersion Index (PDI) of from about 0.25 to about 5.

[0244] Embodiment 18: The polymer of any one of embodiments 1-17, wherein polymer is transparent or semi-transparent (e.g., the polymer has a level of transmittance greater than 50%, such as a level of transmittance greater than 90% at a wavelength from about 300 nm to about 900 nm.

[0245] Embodiment 19: The polymer of any one of embodiments 1-18, wherein the polymer is thermally stable.

[0246] Embodiment 20: The polymer of any one of embodiments 1-19, wherein the polymer is hydrophobic.

[0247] Embodiment 21: The polymer of any one of embodiments 1-20, wherein the polymer has a water contact angle of about 50 degrees or higher.

[0248] Embodiment 22: The polymer of any one of embodiments 1-21, wherein the polymer is hydrophilic.

[0249] Embodiment 23: The polymer of any one of embodiments 1-19 or 22, wherein the polymer has a water contact angle of about 40 degrees or lower.

[0250] Embodiment 24: The polymer of any one of embodiments 1-23, wherein the polymer is biocompatible.Attorney Docket No. 701586-000154WOPT

[0251] Embodiment 25: The polymer of any one of embodiments 1-24, wherein the polymer is non-biodegradable or non-resorbable.

[0252] Embodiment 26: The polymer of any one of embodiments 1-24, wherein the polymer is biodegradable.

[0253] Embodiment 27: The polymer of any one of embodiments 1-26, wherein the polymer is non-immunogenic.

[0254] Embodiment 28: The polymer of any one of embodiments 1-27, wherein the polymer is antifouling.

[0255] Embodiment 29: The polymer of any one of embodiments 1-28, wherein the polymer is a copolymer.

[0256] Embodiment 30: The polymer of any one of embodiments 1-29, wherein the polymer is a block polymer.

[0257] Embodiment 31: A composition comprising a thioether-functionalized cellulose polymer of any one of embodiments 1-30.

[0258] Embodiment 32: The composition of embodiment 31, wherein the composition further comprises a solvent.

[0259] Embodiment 33: The composition of embodiment 32, wherein the solvent is apolar solvent.

[0260] Embodiment 34: The composition of embodiment 32, wherein the solvent is anon-polar solvent.

[0261] Embodiment 35: The composition of embodiment 32, wherein the solvent is a mixture of a polar solvent and a non-polar solvent.

[0262] Embodiment 36: The composition of embodiment 32, wherein solvent is a protic solvent.

[0263] Embodiment 37: The composition of embodiment 32, wherein the solvent is an aprotic solvent.

[0264] Embodiment 38: The composition of embodiment 32, wherein the solvent is an organic solvent.

[0265] Embodiment 39: The composition of embodiment 32, wherein the solvent is an aqueous solvent.

[0266] Embodiment 40: The composition of embodiment 32, wherein the solvent is a green solvent.

[0267] Embodiment 41: The composition of embodiment 32, wherein the solvent is a halogenated solvent.Attorney Docket No. 701586-000154WOPT

[0268] Embodiment 42: The composition of any one of embodiments 31-41, wherein the polymer is present at a concentration of from about 0.01 to about 90% w / w or w / v of the total composition.

[0269] Embodiment 43: The composition of any one of embodiments 31 -42, wherein the polymer is present at a concentration of from about 0.1 to about 50% w / w or w / v of the total composition.

[0270] Embodiment 44: The composition of any one of embodiments 31-43, wherein the polymer is present at a concentration of from about 0.5 to about 7.5% w / w or w / v of the total composition.

[0271] Embodiment 45: The composition of any one of embodiments 31-44, wherein the composition has a viscosity of from about 0.01 to about 250 Pa s.

[0272] Embodiment 46: The composition of any one of embodiments 31-45, further comprising a therapeutic agent.

[0273] Embodiment 47: A film comprising a thioether-functionalized cellulose polymer of any one of embodiments 1-30.

[0274] Embodiment 48: The film of embodiment 47, wherein the film has a thickness of from about 1 pm to about 150 pm.

[0275] Embodiment 49: The film of any one of embodiments 47-48, wherein the film has an average surface roughness from about 5 nm to about 50 nm.

[0276] Embodiment 50: The film of any one of embodiments 47-49, wherein the film is antifouling.

[0277] Embodiment 51: The film of any one of embodiments 47-50, wherein the film undergoes a hydrophobic-to-hydrophilic transition at a surface region with minimal bulk swelling, e.g., under physiological conditions.

[0278]

[0279] Embodiment 52: The film of any one of embodiments 47-51, wherein the film has a higher ultimate interfacial shear strength at failure relative to a film of a same cellulose polymer lacking the thioether substituents.

[0280] Embodiment 53: The film of any one of embodiments 47-52, wherein the film has a ultimate interfacial shear strength at failure is from 2000 kPa to 3500 kPa.

[0281] Embodiment 54: The film of any one of embodiments 47-53, wherein the film has an elastic modulus of from about 200 MPa to about 500MPa in a dry state.

[0282] Embodiment 55: The film of any one of embodiments 47-54, wherein the film has an ultimate tensile strength of from about 20 MPa to about 50 MPa in a dry state.Attorney Docket No. 701586-000154WOPT

[0283] Embodiment 56: The film of any one of embodiments 47-55, wherein the film has an elastic modulus of from about 500 MPa to about 750 MPa in a hydrated state.

[0284] Embodiment 57: The film of any one of embodiments 47-56, wherein the film has an ultimate tensile strength of from about 700 MPa to about 1,100 MPa in a hydrated state.

[0285] Embodiment 58: The film of any one of embodiments 47-57, wherein the film has a surface elastic modulus of from about 200 kPa to about 700 kPa in an oxidized state.

[0286] Embodiment 59: The film of any one of embodiments 47-58, wherein the film is transparent or semi-transparent (e.g., the film has a level of transmittance greater than 50%, such as a level of transmittance greater than 90% at a wavelength from about 300 nm to about 900 nm.

[0287] Embodiment 60: The film of any one of embodiments 47-59, wherein the film has minimal fluorescent scattering.

[0288] Embodiment 61: The film of any one of embodiments 47-60, wherein the film further comprises a therapeutic agent.

[0289] Embodiment 62: The film of embodiment 61, wherein the therapeutic agent is released from the film when the film undergoes a hydrophobic-to-hydrophilic transition.

[0290] Embodiment 63: The film of embodiments 61 or 62, wherein the therapeutic agent is released from the film when the film is exposed to a reactive oxygen species.

[0291] Embodiment 64: The film of embodiments 62 or 63, wherein said release of the therapeutic agent from the film is a controlled release.

[0292] Embodiment 65: The film of any one of embodiments 62-64, wherein said release of the therapeutic agent from the film is a sustained release.

[0293] Embodiment 66: The film of any one of embodiments 47-65, wherein the film is hydrophobic.

[0294] Embodiment 67: The film of any one of embodiments 47-66, wherein the film has a water contact angle of about 50 degrees or higher.

[0295] Embodiment 68: The film of any one of embodiments 47-65, wherein the film is hydrophilic.

[0296] Embodiment 69: The film of any one of embodiments 47-65 or 68, wherein the film has a water contact angle of about 40 degrees or lower.

[0297] Embodiment 70: The film of any one of embodiments 47-69, wherein the film is biocompatible.

[0298] Embodiment 71: The film of any one of embodiments 47-70, wherein the film is non-biodegradable or non-resorbable.

[0299] Embodiment 72: The film of any one of embodiments 47-70, wherein the film is biodegradable.Attorney Docket No. 701586-000154WOPT

[0300] Embodiment 73: The film of any one of embodiments 47-72 wherein the film is non-immunogenic.

[0301] Embodiment 74: The film of any one of embodiments 47-73, wherein the film is antifouling.

[0302] Embodiment 75: The film of any one of embodiments 47-74, wherein the film comprises two or more layers to form a multi-layered film.

[0303] Embodiment 76: The film of embodiment 75, wherein a first layer comprises a first polymer selected from polymers of any of embodiments 1-30 and a second layer comprises a second polymer that is different from the first polymer.

[0304] Embodiment 77: The film of any one of embodiments 47-75, wherein the film is on a surface of a substrate.

[0305] Embodiment 78: The film of embodiment 75, wherein the substrate is a medical device.

[0306] Embodiment 79: A fiber comprising a thioether-functionalized polymer of any one of embodiments 1-30.

[0307] Embodiment 80: The fiber of embodiment 79, wherein the fiber has a diameter between about 1 nm and 5 mm.

[0308] Embodiment 81: A particle comprising a thioether-functionalized cellulose polymer of any one of embodiments 1-30.

[0309] Embodiment 82: The particle of embodiment 81, wherein the particle is a microparticle or a nanoparticle.

[0310] Embodiment 83: The particle of embodiments 81 or 82, wherein the thioether-functionalized cellulose polymer is at a surface of the particle.

[0311] Embodiment 84: The particle of embodiments 82 or 83, wherein the thioether-functionalized cellulose polymer is in an interior of the particle.

[0312] Embodiment 85: The particle of any one of embodiments 81-84, wherein the particle further comprises a therapeutic agent.

[0313] Embodiment 86: The particle of embodiment 85, wherein the therapeutic agent is released from the particle when the particle undergoes a hydrophobic-to-hydrophilic transition.

[0314] Embodiment 87: The particle of embodiments 85 or 86, wherein the therapeutic agent is released from the film when the particle is exposed to a reactive oxygen species.

[0315] Embodiment 88: The particle of embodiments 86 or 87, wherein said release of the therapeutic agent from the particle is a controlled release.

[0316] Embodiment 89: The particle of any one of embodiments 86-88, wherein said release of the therapeutic agent from the particle is a sustained release.Attorney Docket No. 701586-000154WOPT

[0317] Embodiment 90: The particle of any one of embodiments 82-89, wherein the particle has a diameter of between about 1 nm and about 2 microns.

[0318] Embodiment 91: A substrate comprising a coating or film on at least a portion of a surface of the substrate, wherein the coating or film comprises a thioether-functionalized cellulose polymer of any one of embodiments 1-30.

[0319] Embodiment 92: The substrate of embodiment 91, wherein the substrate is a medical device.

[0320] Embodiment 93: The substrate of embodiment 92, wherein the medical device is a catheter, a pacemaker, a drug infusion pump, an implanted optical system, a stent, a vascular graft, a neurostimulator, a cochlear implant, an orthopedic implant, a cardiac lead, a biosensor, an artificial heart valve, an implantable glucose monitor, or an implantable drug depot.

[0321] Embodiment 94: The substrate of any one of embodiments 91-93, wherein the coating or film has a thickness from about 0.1 pm to about 150 pm.

[0322] Embodiment 95: The substrate of any one of embodiments 91-94, wherein the coating or film has a thickness from about 1 pm to about 75 pm.

[0323] Embodiment 96: The substrate of any one of embodiments 91-95, wherein the coating or film has an average surface roughness from about 5 nm to about 50 nm.

[0324] Embodiment 97: The substrate of any one of embodiments 91-96, wherein the coating or film comprises a therapeutic agent.

[0325] Embodiment 98: The substrate of any one of embodiments 91-97, wherein the coating or film the film is hydrophobic.

[0326] Embodiment 99: The substrate of any one of embodiments 91-98, wherein the coating or film has a water contact angle of about 50 degrees or higher.

[0327] Embodiment 100: The substrate of any one of embodiments 91-97, wherein the coating or film is hydrophilic.

[0328] Embodiment 101: The substrate of any one of embodiments 91-97 or 100, wherein the film has a water contact angle of about 40 degrees or lower.

[0329] Embodiment 102: The substrate of any one of embodiments 91-101, wherein the coating or film is biocompatible.

[0330] Embodiment 103: The substrate of any one of embodiments 91-102, wherein the coating or film is non-biodegradable or non-resorbable.

[0331] Embodiment 104: The substrate of any one of embodiments 91-103, wherein the coating or film is non-immunogenic.

[0332] Embodiment 105: The substrate of any one of embodiments 91-104, wherein the coating or film is antifouling.Attorney Docket No. 701586-000154WOPT

[0333] Embodiment 106: A drug-delivery article comprising a thioether-functionalized cellulose polymer of any one of embodiments 1-30 and a therapeutic agent.

[0334] Embodiment 107: The drug delivery article of embodiment 106, wherein the drug delivery article is in the form of a film, a particle, a mesh, a fiber, a gel, a hydrogel, a foam, a mesh, a mat, a non-woven mat, or any combinations thereof.

[0335] Embodiment 108: The drug delivery article of embodiments 106 or 107, wherein the drug delivery article is multilayered.

[0336] Embodiment 109: The drug delivery article of any one of embodiments 106-108, wherein the drug delivery article comprises a coating or film on a surface of substrate, and wherein the coating or film comprises the thioether-functionalized cellulose polymer.

[0337] Embodiment 110: The drug delivery article of any one of embodiments 106-109, wherein the thioether-functionalized cellulose polymer and the therapeutic agent are in a mixture, e.g., homogenous mixture.

[0338] Embodiment 111: The drug delivery article of any one of embodiments 106-109, wherein the thioether-functionalized cellulose polymer and the therapeutic agent are present separately in the drug delivery article.

[0339] Embodiment 112: The drug delivery article of any one of embodiments 106-111, wherein the drug-delivery device is cylindrical, circular or spherical, rectangular, cubic, polyhedron, prism, disc, other geometric shape, or any combinations thereof.

[0340] Embodiment 113: The drug-delivery device of any of embodiments 106-112, wherein the drug delivery article is in form of an implant or an implantable device.

[0341] Embodiment 114: A method for controlling the release of a therapeutic agent, the method comprising: (a) providing a drug-delivery article of any of embodiments 106-113; and (b) inducing a hydrophobic-to-hydrophilic transition in the thioether functionalized cellulose polymer.

[0342] Embodiment 115: A method of forming a coating on a surface of a substrate, the method comprising applying a thioether-functionalized cellulose polymer of any one of embodiments 1-30 to at least a portion of a surface of the substrate.

[0343] Embodiment 116: The method of embodiment 115, wherein the step of coating at least a portion of a surface of the substrate comprises dip coating, spray coating, spin coating, drop casting, roll coating, or any combination thereof.

[0344] Embodiment 117: The method of embodiments 115 or 116, wherein the substrate is a medical device.

[0345] Embodiment 118: The method of any one of embodiments 115-117, wherein the polymer is applied as a solution.Attorney Docket No. 701586-000154WOPT

[0346] Embodiment 119: The method of embodiment 118, further comprising a step of removing a solvent from the solution comprising the polymer after forming the coating or film.

[0347] Embodiment 120: The method of embodiment 115, wherein the method comprises applying a solution comprising the polymer to a mold and removing a solvent from the solution after applying to the mold.

[0348] Embodiment 121: The method of embodiments 119 or 120, wherein step of removing the solvent comprises temperature and / or pressure-controlled vaporization of the solvent.

[0349] Embodiment 122: The method of any one of embodiments 115-121, further comprising a step of drying the substrate after the step of applying the polymer.

[0350] Embodiment 123: The method of embodiment 122, wherein said drying step is under vacuum.

[0351] Embodiment 124: The method of embodiments 122 or 123, wherein said drying step is at a temperature higher than room temperature.

[0352] Embodiment 125: The method of any one of embodiments 115-124, wherein the coating or film comprises a therapeutic agent.

[0353] Embodiment 126: A method for preparing a thioether-functionalized cellulose polymer, the method comprising reacting a cellulose polymer with a thioether-functionalizing reagent.

[0354] Embodiment 127: The method of embodiment 126, wherein the thioether-functionalizing reagent is an isothiocyanate-based thioether-functionalizing reagent.

[0355] Embodiment 128: The method of embodiments 126 or 127, wherein the thioether-functionalizing reagent is 3-(methylthio)propyl isothiocyanate.

[0356] Embodiment 129: The method of any one of embodiments 126-128, wherein the polymer is hydroxyethyl cellulose (HEC) or methyl cellulose (MC) or Hydroxy propyl methylcellulose (HPMC).

[0357] Embodiment 130: The method of any one of embodiments 126-129, wherein the polymer is hydroxyethyl cellulose.

[0358] Embodiment 131: The method of any one of embodiments 126-130, wherein the cellulose polymer is hydroxyethyl cellulose.

[0359] Embodiment 132: The method of any one of embodiments 126-131, wherein the thioether-functionalized cellulose polymer is a polymer of any one of embodiments 1-30.

[0360] Embodiment 133: A polymeric mesh, foam, or hydrogel comprising a thioether-functionalized cellulose polymer of any of embodiments 1-30.DefinitionsAttorney Docket No. 701586-000154WOPT

[0361] For convenience, certain terms employed herein, in the specification, examples and appended claims are collected herein. Unless stated otherwise, or implicit from context, the following terms and phrases include the meanings provided below. Unless explicitly stated otherwise, or apparent from context, the terms and phrases below do not exclude the meaning that the term or phrase has acquired in the art to which it pertains. The definitions are provided to aid in describing particular embodiments, and are not intended to limit the claimed invention, because the scope of the invention is limited only by the claims. Further, unless otherwise required by context, singular terms shall include pluralities and plural terms shall include the singular.

[0362] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as those commonly understood to one of ordinary skill in the art to which this invention pertains. Although any known methods, devices, and materials may be used in the practice or testing of the invention, the methods, devices, and materials in this regard are described herein.

[0363] Where a range of values is provided, it is understood that each intervening value, to the tenth of the unit of the lower limit unless the context clearly dictates otherwise, between the upper and lower limit of that range and any other stated or intervening value in that stated range, is encompassed within the invention. The upper and lower limits of these smaller ranges may independently be included in the smaller ranges and are also encompassed within the invention, subject to any specifically excluded limit in the stated range. Where the stated range includes one or both of the limits, ranges excluding either or both of those included limits are also included in the invention.

[0364] Certain ranges are presented herein with numerical values being preceded by the term “about.” The term “about” is used herein to provide literal support for the exact number that it precedes, as well as a number that is near to or approximately the number that the term precedes. In determining whether a number is near to or approximately a specifically recited number, the near or approximating unrecited number may be a number which, in the context in which it is presented, provides the substantial equivalent of the specifically recited number.

[0365] As used herein the term “comprising” or “comprises” is used in reference to compositions, methods, and respective component(s) thereof, that are essential to the invention, yet open to the inclusion of unspecified elements, whether essential or not. In other words, except where the context requires otherwise, the term “comprise” and variations of the term, such as “comprising”, “comprises” and “comprised”, are not intended to exclude further additives, components, integers or steps.

[0366] The singular terms “a,” “an,” and “the” include plural referents unless context clearly indicates otherwise. Similarly, the word “or” is intended to include “and” unless the contextAttorney Docket No. 701586-000154WOPTclearly indicates otherwise. It is further noted that the claims can be drafted to exclude any optional element. As such, this statement is intended to serve as antecedent basis for use of such exclusive terminology as “solely,” “only” and the like in connection with the recitation of claim elements, or use of a “negative” limitation.

[0367] As used herein the term “acyl” refers to a group of the Formula — CO — Cnwherein Cnrepresent a straight or branched alkyl chain wherein n can be 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10.

[0368] As used herein a “ester” refers to a group of the formula — C(O) — OCnCnrepresent a straight or branched alkyl chain wherein n can be 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10. For example a chemical compound derived from an acid in which at least one — OH (hydroxyl) group is replaced by an — O-alkyl (alkoxy) group.

[0369] As used herein the term “alkyl”, whether alone or as part of a substituent group, refers to a saturated Ci-Cncarbon chain, wherein the carbon chain may be straight or branched; wherein n can be 2, 3, 4, 5, 6, 7, 8, 9 or 10. Suitable examples include, but are not limited to methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, t-butyl, n-pentyl and n-hexyl. With reference to substituents, the term “independently” means that when more than one of such substituents is possible, such substituents may be the same or different from each other. “Carboxyl” refers to the — CO2H substituent.

[0370] “Carbonyl” refers to a — C(O) —, — (CO) — or — C(=O) — group. All notations are used interchangeably herein. “Oxo” refers to a =0 substituent

[0371] ‘Thio” or “thiol” refer to a-SH substituent.

[0372] ‘Halo” or “halogen” refers to bromo (bromine), chloro (chlorine), fluoro (fluorine), or iodo (iodine). Compound words have the meaning of the individual functional groups or fragments as would be understood in the art. For example, “hydroxyalkyl” refers to the -(alkyl)-OH substituent, “thioalkyl” refers to the -(alkyl)-SH substituent, “cyanoalkylene” refers to the -(alkylene)C=N substituent; “hydroxyalkylene” refers to the -(alkylene)OH substituent; “arylmethoxy” refers to a methoxy substituted aryl group.

[0373] The term “optionally substituted” means that the specified group or moiety is unsubstituted or is substituted with one or more (typically 1, 2, 3, 4, 5 or 6 substituents) independently selected from the group of substituents listed below in the definition for “substituents” or otherwise specified. The term “substituents” refers to a group “substituted” on a substituted group at any atom of the substituted group. Suitable substituents include, without limitation, halogen, hydroxyl, caboxy, oxo, nitro, haloalkyl, alkyl, alkenyl, alkynyl, alkaryl, aryl, heteroaryl, cyclyl, heterocyclyl, aralkyl, alkoxy, aryloxy, amino, acylamino, alkylcarbanoyl, arylcarbanoyl, aminoalkyl, alkoxycarbonyl, carboxy, hydroxylalkyl, alkanesulfonyl, arenesulfonyl, alkanesulfonamido, arenesulfonamido, aralkylsulfonamido, alkylcarbonyl, acyloxy, cyano orAttorney Docket No. 701586-000154WOPTureido. In some cases, two substituents, together with the carbons to which they are attached to can form a ring.

[0374] In some embodiments, an optionally substituted group is substituted with 1 substituent. In some other embodiments, an optionally substituted group is substituted with 2 independently selected substituents, which can be same or different. In some other embodiments, an optionally substituted group is substituted with 3 independently selected substituents, which can be same, different or any combination of same and different. In still some other embodiments, an optionally substituted group is substituted with 4 independently selected substituents, which can be same, different or any combination of same and different. In yet some other embodiments, an optionally substituted group is substituted with 5 independently selected substituents, which can be same, different or any combination of same and different.

[0375] The term “statistically significant" or “significantly" refers to statistical significance and generally means a two standard deviation (2SD) or greater difference.

[0376] Groupings of alternative elements or embodiments of the invention disclosed herein are not to be construed as limitations. Each group member can be referred to and claimed individually or in any combination with other members of the group or other elements found herein. One or more members of a group can be included in, or deleted from, a group for reasons of convenience and / or patentability. When any such inclusion or deletion occurs, the specification is herein deemed to contain the group as modified thus fulfilling the written description of all Markush groups used in the appended claims.

[0377] It should be understood that this invention is not limited to the particular methodology, protocols, and reagents, etc., described herein and as such can vary. The terminology used herein is for the purpose of describing particular embodiments only, and is not intended to limit the scope of the present invention, which is defined solely by the claims.

[0378] The section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described. All documents, or portions of documents, cited in this application, including, but not limited to, patents, patent applications, articles, books, and treatises, are hereby expressly incorporated by reference in their entirety for any purpose.

[0379] The description of embodiments of the disclosure is not intended to be exhaustive or to limit the disclosure to the precise form disclosed. While specific embodiments of, and examples for, the disclosure are described herein for illustrative purposes, various equivalent modifications are possible within the scope of the disclosure, as those skilled in the relevant art will recognize. For example, while method steps or functions are presented in a given order, alternative embodiments may perform functions in a different order, or functions may be performedAttorney Docket No. 701586-000154WOPTsubstantially concurrently. The teachings of the disclosure provided herein can be applied to other procedures or methods as appropriate. The various embodiments described herein can be combined to provide further embodiments. Aspects of the disclosure can be modified, if necessary, to employ the compositions, functions and concepts of the above references and application to provide yet further embodiments of the disclosure. These and other changes can be made to the disclosure in light of the detailed description. All such modifications are intended to be included within the scope of the appended claims.

[0380] Specific elements of any of the foregoing embodiments can be combined or substituted for elements in other embodiments. Furthermore, while advantages associated with certain embodiments of the disclosure have been described in the context of these embodiments, other embodiments may also exhibit such advantages, and not all embodiments need necessarily exhibit such advantages to fall within the scope of the disclosure.

[0381] Other terms are defined herein within the description of the various aspects of the invention.

[0382] The technology described herein is further illustrated by the following examples which in no way should be construed as being further limiting.EXAMPLES

[0383] Example 1: Thioether-Functionalized Cellulose for the Fabrication of Oxidation-Responsive Biomaterial Coatings and Films

[0384] Biomaterial coatings and films can prevent premature failure and enhance performance of chronically implanted medical devices. However, current hydrophilic polymer coatings and films have significant drawbacks, including swelling and delamination. To address these issues, we modified hydroxyethyl cellulose with thioether groups to generate an oxidation-responsive polymer, HECMTP. HECMTP readily dissolves in green solvents and can be fabricated as coatings or films with tunable thicknesses. HECMTP coatings effectively scavenge hydrogen peroxide, resulting in conversion of thioether groups to sulfoxide groups on the polymer chain. Oxidation-driven, hydrophobic-to-hydrophilic transitions that are isolated to the surface of HECMTP coatings under physiologically relevant conditions increase wettability, decrease stiffness, and reduce protein adsorption to generate a non-fouling interface with minimal coating delamination or swelling. HECMTP can be used in diverse optical applications and permits oxidation-responsive, controlled drug release. HECMTP films are non-resorbable in vivo and evoke minimal foreign body responses. These results highlight the versatility of HECMTP and support its incorporation into chronically implanted medical devices.Attorney Docket No. 701586-000154WOPT

[0385] Chronically implanted medical devices, such as pacemakers1, catheters2, electrodes-, pumps211and prostheses,21are used widely for monitoring and treating disease. Despite successful clinical implementation, these devices can experience various problems that cause premature device failure.— Biomaterials formulated as coatings, which adhere or bond to the device surface, or films, which can be press-fit as a separate material layer onto devices, can prevent premature failure of chronically implanted medical devices as well as enhance their functionality and performance— Employing hydrogel- and hydrophilic polymer-based coatings or films of polyethylene glycol (PEG),12111zwitterionic polymers (e.g. polycarboxybetaine, polysulfobetaine),1211211or other synthetic polymers12112improves long-term medical device performance by altering device surface chemistry, wettability, topography, and / or mechanical properties. Coating- or film-derived surface modifications mitigate molecular and cellular fouling and thrombosis, reduce foreign body response (FBR)-mediated inflammation, and minimize fibrotic encapsulation that would otherwise cause the formation of opaque, cell-dense, fibrotic scar tissue layers around uncoated devices.12-19 22Biomaterial coatings and films can also reduce the mechanical stiffness mismatch at the implant-tissue interface to minimize the activation of mechanosensitive receptors,19120122limit friction and wear,22121mitigate damage from device micromotion,— and prevent corrosion and subsequent device degradation,— thereby attenuating pro-inflammatory macrophage states and the fibroblast to myofibroblast transitions that promote capsular contracture. Naturally-derived biomolecules and extracellular matrix (ECM) proteinbased coatings and films have also been incorporated as biomimetic substrates on devices to limit immune recognition and enhance device-tissue integration.22^21Aside from regulating FBR and cell interactions, biomaterial coatings and films can be imparted with additional traits to improve longterm device performance including antimicrobial resistance to prevent biofilm formation, controlled local small molecule drug release, and localized gene or viral vector delivery —

[0386] Despite conferring important functions to medical devices, currently available biomaterial coatings and films still have significant drawbacks. Hydrophilic polymer coatings implanted in a dehydrated state can swell greater than 3 times in size in vivo, leading to increased compressive tissue damage, increased impedance, coating delamination from the underlying device, and patient discomfort.2221Coatings and films applied as soft, hydrated polymers can also easily delaminate or shear off during implantation, leading to the exposure of the underlying surface of the implant, which can stimulate deleterious FBRs — Hydrophilic polymers delaminated from devices also pose an increased embolism risk and can disseminate and deposit at distant tissue sites away from the implant, leading to persistent, non-healing abscesses — Direct chemical bonding of hydrophilic polymers to the device surface can overcome delamination issues but requires specialized surface preparation that cannot be applied to all devices.1222Natural ECM-basedAttorney Docket No. 701586-000154WOPTcoatings and films suffer from sourcing and scaling issues, as well as increased immunogenic risk.^1To address these issues, materials engineering approaches are needed to generate new hydrophilic, non-fouling biomaterials that can be stably incorporated onto medical devices, so that they are resistant to disruption during implantation, persist chronically, and do not significantly swell in vivo. Additionally, beyond satisfying these general specifications, applications of biomaterial coatings and films could require other context-dependent properties, such as limited light scattering for optical devices, minimal impedance for electrical recording and stimulation, or the ability to elute drugs to direct local biological actions. Cost and manufacturability should also be considered for the effective scale up and clinical translation of coating and film technologies.

[0387] Cellulose-based materials have been used in industrial coating applications dating back to the late 1800’s, starting with water repellent, scratch resistant, nitrocellulose-based lacquers — Due to their natural abundance and renewable sourcing, coatings and films derived from cellulose esters have become ubiquitous in many diverse industrial applications including: dialysis and filtration membranes (regenerated cellulose),— photography film and coatings on drug formulations to modify release kinetics (cellulose esters, including cellulose acetate and cellulose acetate butyrate), lacquer coatings (cellulose acetate butyrate),4246 49and tape (cellulose acetate) — Across all these applications, chemical modification of the hydroxyls on the repeating anhydroglucose unit of cellulose confers emergent and modular properties, including the ability to be dissolved in organic solvents and increased hydrophobicity necessary to repel water.^-^ Cellulose-based materials have received only limited use as coatings or films on chronically implanted medical devices because hydrophilic derivatives swell, readily delaminate, and have challenging solubility profiles for fabrication — Although cellulose esters have improved solubility profiles in organic solvents, which allows them to form effective coatings or films, their poorer surface wettability compared to hydrophilic polymers causes increased protein and cell fouling that impacts overall biocompatibility. New cellulose derivatives that afford the processability of cellulose esters to generate effective coatings and films, while also facilitating the hydrophilic interface necessary for enhanced biocompatibility, would be broadly appealing for use with chronically implanted medical devices.

[0388] Here, we derived a new, smart, cellulose-based material that can be readily formulated as a coating or film, persists chronically in vitro and in vivo, and enables the generation of a soft, non-fouling, hydrophilic interface with minimal material swelling. To achieve this, we leveraged chemistry bioinspired by methionine-based materials— to endow a specific cellulose polymer, hydroxyethyl cellulose (HEC), with thioether groups and confer oxidation-responsive properties. Upon oxidation under physiologically relevant conditions, this new thioether-functionalized cellulose readily transitions from a hydrophobic to a hydrophilic polymer via the conversion of theAttorney Docket No. 701586-000154WOPTpendant thioethers to sulfoxide groups. We hypothesized that a thioether-functionalized, cellulose material would be soluble in organic solvents and thus processable as both coatings or fdms and that the exposed surface of these preparations would be readily oxidizable in vivo by physiological concentrations of reactive oxygen species, leading to the formation of a substrate that is more hydrophilic, non-fouling, and soft, which would confer enhanced biocompatibility. To test this hypothesis, we synthesized the thioether-functionalized cellulose polymer, HECMTP, at large scales using a robust, single step isothiocyanate-based reaction, and investigated its ability to serve as an effective biomaterial coating and film. HECMTP readily dissolves in organic solvent systems, and coating outcomes, such as thickness and surface roughness, could be tuned by adjusting composition and fabrication parameters. Treatment of HECMTP-coated substrates with physiological concentrations of hydrogen peroxide in vitro resulted in selective oxidation of thioether groups that served to increase surface hydrophilicity, decrease the effective surface mechanical stiffness, and reduce the extent of protein adsorption and neural cell fouling while causing negligible material swelling. We demonstrated the utility of HECMTP coatings for optical applications and HECMTP films for oxidation-responsive controlled release of molecules. HECMTP films persist in vivo for at least 4 weeks when implanted subcutaneously and show minimal immune cell recruitment and fibrotic scarring compared to equivalent non-oxidation responsive cellulose biomaterials. Our findings demonstrate the feasibility of using this oxidation-responsive, thioether-functionalized cellulose platform to improve the function and longevity of chronically implanted medical devices.

[0389] Thioether-functionalized cellulose (HECMTP) is an oxidation-responsive polymer:We selected hydroxyethyl cellulose (ELEC) as a template cellulose polymer for postpolymerization modification with thioether groups as it is highly abundant, inexpensive, has been previously used in medical applications, and is commercially available in numerous molecular weights. ELEC contains accessible primary hydroxyls on the repeating anhydroglucose unit that can be used as nucleophilic species in isothiocyanate- and isocyanate-based reactions. ELEC (Mw 430kDa (GPC), FIG.8A) was reacted with excess 3-(methylthio)propyl isothiocyanate in dimethyl sulfoxide (DMSO) with n,n-diisopropyl ethylamine (DIEA) as a catalyst to generate a new polymer, HECMTP, which has 3-(methylthio)propyl (MTP) groups attached to the HEC polymer backbone by a stable thiocarbamoyl linker (FIG. 1A, Table 1). HECMTP could be prepared with 5-23 mol% MTP functionalization relative to the available free primary hydroxyls, with moderate control of functionalization achieved through tuning reaction stoichiometry (FIGs. IB, 1C, 8A-8D) While HEC readily dissolved in water to form a viscous solution, HECMTP at functionalities as low as 9 mol% formed hydrated gels, and at functionalities greater than 15 mol% was insoluble in water (FIGs. ID, 8A-8D) Based on an initial screen of different functionalizations, HECMTPAttorney Docket No. 701586-000154WOPTwith MTP functionalization at an average of 21 mol%, or -0.63 MTP groups per estimated anhydroglucose unit repeat, was selected for detailed evaluation. All studies reported here were completed using a single batch of HECMTP that was derived by blending the yields from 4 individual, 1 gram-scale reactions of near equivalent functionality (Table 2, FIG.9B).

[0390] To determine whether thioether groups on HECMTP could be oxidized to generate the sulfoxide-functionalized polymer, designated as HECso, we exposed HECMTP to oxidizing conditions for one day using 1% (327mM) hydrogen peroxide (H2O2) (FIG. IE). Conversion of thioether groups to sulfoxide groups was detected by1H NMR as a readily identifiable shift in the thioether methyl protons from 2.15 ppm to 2.92 ppm (FIG. IF) — Using 1% H2O2, all thioether groups were converted to sulfoxide groups, verified by complete loss of the thioether methyl protons at 2.15 ppm (FIGs. IF, 9A-9C). By FTIR, HECMTP showed emergent -CS-NH- and -O-CS- (thiocarbamoyl) stretches at 1535 cm’1and 1710 cm’1respectively following MTP addition,while oxidation of HECMTP to HECso showed characteristic emergence of a S=O stretch at 1055 cm’1(FIG. Under the 1% H2O2 oxidation conditions, the FTIR spectra within the thiocarbamoyl region showed a notable increase in the intensity of the 1710 cm’1stretch and a concurrent reduction in the 1535 cm’1stretch which is consistent with the sulfur atom in the thiocarbamoyl being substituted by an oxygen atom to form -O-CO-NH- (FIG. 1G).— Despite these changes, there was preserved total integration of the two stretches within the thiocarbamoyl region (FIGs. 10A-10B).

[0391] Following oxidation, there was a reduction in the total integrated area of methyl protons by NMR in HECso samples compared to unmodified HECMTP. We suspected that the attenuated total detected sulfoxide-associated methyl protons on HECso by NMR was a result of significantly reduced solubility in dTFA (deuterated trifluoroacetic acid) as well as other common NMR solvents, whereas HEC and HECMTP dissolved completely in dTFA and returned clean NMR spectra. Oxidizing HECMTP with lower concentrations of H2O2 within the physiological range (80-320pM) for one day resulted in partial oxidation of the polymer, such that it was still completely soluble in dTFA for NMR evaluation. Under these dilute oxidizing conditions, we detected partial conversion of thioether groups to sulfoxides and preservation of methyl protons by NMR, implying no cleavage of functionalized groups from the HEC backbone (FIG. 10C). Evaluation of HECMTP samples before and after oxidation by X-ray photoelectron spectroscopy (XPS) also corroborated the preservation of sulfur content on the polymer after oxidation (FIG. 11). We did not detect any notable changes to stretches in the thiocarbamoyl region by FTIR in these samples implying preferential thioether oxidation over thiocarbamoyl oxidation upon exposure to physiological concentrations of H2O2 (FIG. 12). The template polymer, HEC, was not altered following one day of 1% H2O2 exposure, which indicated that there was no detectable oxidation of ethylene oxideAttorney Docket No. 701586-000154WOPTgroups on the polymer backbone to which MTP groups were linked (FIGs.13A-13C). Collectively, these data demonstrate that there was negligible cleavage of the MTP group from the HEC polymer backbone after oxidation and preferential oxidation of the thioether moiety, consistent with previous reports using similar chemistries.^^ Characterization of HECMipby differential scanning calorimetry (DSC) and thermal gravimetric analysis (TGA) showed that HECMTP was thermally stable up to 215°C, making it amenable to a wide range of processing conditions and methods (FIG. 14A-14C).

[0392] To assess differences in wettability between HEC variants, we performed sessile-drop goniometry on casted fdms of HEC, HECMTP, and HECso to evaluate relative hydrophilic-hydrophobic character. As anticipated, MTP functionalization resulted in a significant decrease in wettability, with HECMTP displaying a contact angle of 67° which was more than double that of the unmodified HEC (24°) and within the range of reported values for other cellulose ester benchmarks (FIG. 1H) — Oxidation of HECMTP to HECso yielded a significant 48° decrease in contact angle, resulting in a surface that had equivalent wettability to HEC, demonstrating that oxidation with 1% H2O2 is an effective chemical stimulus to substantially increase the hydrophilicity of this thioether-functionalized cellulose by converting thioether functional groups to sulfoxides (FIG. 1H).

[0393] Collectively, these data show that HEC can be readily modified with thioether functionalities at high scale and with stoichiometric control to generate a new, oxidation responsive polymer, HECMTP. Oxidation of HECMTP prompted sulfoxide conversion but no pendant group cleavage and was sufficient to transition HECMTP from a water insoluble polymer to a hydrophilic polymer. Since HECMTP possessed the unique capacity to be processed using organic solvents like a cellulose ester but also to selectively transition into a hydrophilic interface via a ubiquitous biological stimulus, we were prompted to explore in earnest its potential as a coating and film for biomedical applications.

[0394] HECMTP can be fabricated as a coating or film: Dip coating is a standard industrial technique for processing coatings of cellulose esters with coating properties, including thickness and surface finish, readily altered by key formulation parameters such as solvent system and temperature.^2To determine an appropriate solvent system in which HECMTP could be solubilized for coating applications, we prepared HECMTP at lOmg / mL in common green organic solvents including DMSO, methanol, ethanol, isopropyl alcohol (IPA), acetone, and water. At this relatively dilute concentration, HECMTP was soluble in DMSO but was insoluble, and did not disperse, in any of the other solvents (FIG. 2A). To identify a wider range of useful solvent systems for preparing HECMTP, we generated and tested blends of DMSO with the same array of green organic solvents at 50% / 50% v / v composition. HECMTP was soluble in all DMSO blended solvent systems except for DMSO / water in which an insoluble, dispersed polymer phase was noted (FIG.2B).Attorney Docket No. 701586-000154WOPT

[0395] Viscosity of cellulose solutions influences the thickness and regularity of finished coatings, as well as its workability during processing.^2Therefore, we next used rheological testing to assess the effect of solvent system, polymer concentration, and temperature on the viscosity of HECMTP solutions. The composition of DMSO / organic solvent blends impacted HECMTP solution viscosity, with increasing proportions of acetone in a DMSO / acetone blend resulting in a dramatic increase in the viscosity of 5wt% HECMTP solutions, ranging from 15.1 Pa. s at 0% acetone to 119.8 Pa.s with 50% acetone incorporation (FIG. 2C). Increasing the concentration of HECMTP in DMSO-only formulations from lwt% to 3wt% also caused a significant increase in viscosity from 0.09 to 1.6 Pa.s, while the viscosity of 5wt% preparations increased by an order of magnitude to 15.1 Pa.s (FIG. 2D). There was a notable effect of temperature on HECMTP solution viscosity, and we observed a significant, linear decrease in viscosity from 10 Pa.s at 30°C to 2.0 Pa.s at 70°C (FIGs. 15A-15B). Taken together, these data suggest that HECMTP solution viscosity can be readily tuned across 3 orders of magnitude by adjusting polymer concentration, solvent system, and temperature at processing.

[0396] We next tested how HECMTP solution viscosity influences the thickness and roughness of prepared coatings. We used acid-cleaned glass slides and dipped HECMTP solutions at a fixed rate of 1 mm / sec (the fastest rate that still approximately maintains zero-shear viscosity or a shear rate of 1 sec'1) and allowed slides to dry in a vacuum oven at 40°C for at least 72 hours to remove residual DMSO solvent and form the coating (FIG.2E). We identified differences in the thickness of HECMTP coatings prepared from different DMSO / acetone blends at 5wt% HECMTP with all formulations resulting in coatings with a thickness ranging from 10-25pm (FIGs. 2F, 15C-15D).There was a notable change in surface roughness due to solvent blending, with 50% DMSO / acetone solutions demonstrating large, undulating surface roughness on the micron scale and a significantly higher average roughness (~29.6nm) that was more than double that of the 100% DMSO solvent system (12.7nm) (FIGs. 16A, 16D). To test the effect of polymer solution concentration on coating thickness and roughness, we prepared dip coated slides at 1, 3, and 5wt% in DMSO only. Increasing the solution’s polymer concentration significantly increased the coating thickness from 1.9pm at 1 wt% to 14.1 pm at 3wt%, but there was minimal increase in coating thickness between the 3wt% and 5wt% preparations (FIG. 15D). Surface profilometry of these coatings revealed that there was a large increase in roughness from lwt% to 3wt%, but an apparent smoothing at 5wt% (FIGs. 16B, 16E), suggesting that the higher wt% coating may deposit a significantly greater total amount of HECMTP, effectively creating a smoother and more uniform coating. Scanning electron microscopy (SEM) micrographs of HECMTP coatings applied to aluminum stubs mirrored this trend. While 3wt% HECMTP preparations had essentially featureless surfaces (FIG. 16G), lwt% HECMTP coatings showed regular, dimple-like features approximately 2pm in diameter, suggesting that thisAttorney Docket No. 701586-000154WOPTlower HECMTP concentration was insufficient to cleanly coat the substrate (FIG. 16H). These data demonstrate that HECMTP coatings, when prepared at appropriate concentrations, could effectively smooth the surface of a roughened underlying substrate. When comparing all the different formulations together, HECMTP coating thickness was directly proportional to the measured magnitude of viscosity of the coating solution irrespective of solvent system or concentration (FIG.2F). We also evaluated the effects of fabricating multilayer coatings by dipping a substrate in a solution of 5wt% HECMTP in DMSO and incorporating a 24 hour drying step between subsequent dips. Increasing from 1 to 3 dips resulted in a significant increase in coating thickness from 12.6 to 26.4pm (FIG.2G). Evaluating the average roughness, we observed a small, but significant increase from 1 dip at 12.7nm to 3 dips at 34.3nm (FIGS.2H, 16C, 16F).

[0397] To form free-standing films from HECMTP, we first fabricated a silicone mold composed of two, press-fit silicone sheets (FIG.21). HECMTP in DMSO was pipetted to fill the silicone mold cavity and dried in a vacuum oven at 40°C to form a large free-standing film. Individual wafers of defined geometries could be punched out from larger film preparations using a biopsy punch, enabling a rapid and scalable approach to film fabrication (FIG. 21). By depositing a layer of HECMTP solution every 24 to 48 hours we could tune film thickness from 6.8pm (1 layer) to 66.6 pm (3 layers) with no evidence of lamination defects within multilayered constructs (FIG. 2J).These data show that HECMTP can be dissolved in green organic solvents and processed to form coatings and films whose thickness and roughness can be readily tuned through careful selection of solvent and processing parameters.

[0398] HECMTP coatings are oxidation-responsive and stable under simulated physiological conditions: Next, we evaluated the physical and oxidation-responsive properties of HECMTP when formulated as a coating. To elucidate structure-function correlates for HECMTP coatings, we synthesized two other HEC derivatives to serve as benchmarking controls: (i) HECHEX, which contains a thiocarbamoyl linked aliphatic hexyl group of similar length to that on HECMTP but without the thioether functionality, and (ii) HECOCT, which contains an aliphatic octyl group linked to the polymer backbone by a carbamate linker (FIGs. 17A-17G, 18A-18C, Tables 3 and 4). HECHEX and HECOCT were appropriate functional controls for evaluating the physical and oxidation-responsive properties of HECMTP as they were synthesized via equivalent chemistries (isothiocyanate and isocyanate reactions respectively), had similar hydrophobicity to the MTP group, and both lacked thioether functionality. However, important limitations with the fabrication of HECHEX and HECOCT benchmarking controls warrant brief review here. Due to the limited reactivity of hexyl isothiocyanate, HECHEX could only be functionalized to approximately 5 mol% hexyl groups on the polymer chain, which was considerably less than the 21 mol% functionalization that could be readily achieved for HECMTP. HECOCT, by virtue of employing moreAttorney Docket No. 701586-000154WOPTreactive isocyanate rather than isothiocyanate chemistries in its synthesis, could be readily tuned up to 100 mol% functionality. However, at functionalities of 12 mol% and higher, we observed issues with HECOCT solubility whereby the polymer would either be insoluble in DMSO or would solubilize with mild heating but rapidly crystallize as it cooled (FIG. 19). In an attempt to address this issue, we tested 18mol% HECOCT in a variety of different solvent formulations, including: water, acetone, toluene, and 50 / 50 DMSO / toluene (FIG. 20). HECOCT at 18 mol% octyl functionalization formed swollen hydrogels in water, was insoluble in acetone and toluene, and was only partially soluble in 50 / 50 DMSO / toluene, preventing its effective formulation as a freestanding film or coatings. Therefore, with consideration of the above limitations, HECHEX at 5 mol% hexyl and HECOCT at 8 mol% octyl groups were used to fabricate coatings for comparisons with HECMTP coatings.

[0399] As a first test of the oxidation-responsive properties of HECMTP coatings, we drop-casted HECMTP and benchmarking polymers into wells of a 96 well plate to form thin coatings that were incubated overnight in lOOpL of 4mM hydrogen peroxide at 37°C, which equated to an approximate 2:1 molar ratio of MTP moieties to H2O2. At 24 hours, HECMTP coatings had scavenged 82.8% (or 1046.5 pmol / cm2) of the available H2O2 whereas HEC and HECOCT coatings did not scavenge any detectable amount of H2O2 (FIG. 3A). HECHEX scavenged a small but significant amount of incubated H2O2 (15.6%), likely through oxidation of the thiocarbamoyl linker as noted earlier (FIG. 3A). FTIR-based comparisons of HEC, HECHEX, HECOCT, and HECMTP before and after oxidation with 1% H2O2 confirmed that both HECHEX and HECMTP had H2O2-induced changes in the two stretches in the thiocarbamoyl region consistent with the sulfur atom on the thiocarbamoyl being substituted for by an oxygen atom— (FIGs. 21A-21D). HEC and HECOCT showed no apparent change in their respective FTIR spectra after oxidation which further strengthened our confidence in the assessment that the thiocarbamoyl was altered in the HECHEX and HECMTP polymers under these millimolar-range H2O2 conditions.

[0400] To profile the kinetics of HECMTP oxidation we assessed the amount of H2O2 scavenged at defined time points from 1 hour to 7 days (FIG.3B). H2O2 scavenging by HECMTP demonstrated second order rate kinetics resulting in a sigmoidal time dependency, which was consistent with an autocatalytic process that has previously been observed in polysulfide-based materials— (FIG.22A), with nearly all H2O2 (>99%) consumed following one week of incubation. HECMTP coatings scavenged H2O2 in a concentration dependent manner which was directly proportional to the initial concentration of applied H2O2 within the concentration range of 80pM to 8mM (FIG. 3C). To further dissect the concentration and load dependent effects, we exposed HECMTP coatings to either lOOpL of H2O2 at 4mM or 200pL of H2O2 at 2mM to evaluate different concentrations but conserved total molar equivalents of H2O2. After 24 hours, the HECMTP coatings had scavengedAttorney Docket No. 701586-000154WOPT82% of the 4mM H2O2 but only 55% of the 2mM H2O2, demonstrating the strong dependency of H2O2 concentration on the scavenging rate of the film (FIG. 22B). We also noted a finite H2O2 scavenging capacity for HECMTP coatings that affected scavenging kinetics, such that high initial H2O2 loads (8mM) reduced the effective scavenging rate of the coating upon subsequent exposure to a second 4mM H2O2 solution (FIG. 22C). By contrast, HECMTP coatings exposed to a 100-fold lower initial H2O2 load (80pM) could more effectively scavenge the 4mM H2O2 solution upon subsequent exposure (FIG.22C).

[0401] At sites of tissue injury and cell death in vivo, reactive oxygen species (ROS) are generated at concentrations ranging from l-100pM, with exposure to 80-100pM ROS capable of causing oxidative stress-mediated cell necrosis or apoptosi s.2222We assessed how H2O2 scavenging by HECMTP coatings within such physiological ROS concentrations altered the surface wettability of the coating. Exposing HECMTP coatings to H2O2 concentrations at or greater than 40pM for one day, caused a significant decrease in contact angle with 320pM H2O2 incubation resulting in contact angles indistinguishable from HECso, which defined the maximum wettability of the surface (FIG.3D) To assess whether the maximum wettability of the surface could be achieved by prolonged exposure to lower, physiologically relevant concentrations of H2O2, we incubated HECMTP coatings in 80pM H2O2 for 7 days. Under these milder oxidizing conditions, HECMTP coatings gradually transitioned to be maximally wettable over the course of 7 days with the greatest rate of change occurring from 1 to 3 days of incubation (FIG.3E). HECMTP incubated in PBS only showed a small change in contact angle over the 7 day incubation period indicative of a low amount of hydration of the polymer coating, but such effects on surface wettability paled in comparison to those induced by the oxidizing conditions (FIG.3E). Contact angle measurements were paired with bulk physical evaluations including coating swelling and dry mass loss (FIGs. 3F-3G, 23). The wet mass of HECMTP coatings changed minimally over the course of 7 days when incubated in PBS only, while the gradual hydrophobic to hydrophilic surface transition provoked by oxidation with 80pM H2O2 caused a concurrent increase in coating wet mass that reached 67.7% by 7 days (FIGs. 3F, 23).This change in material wet mass was small and insignificant when compared to the HECHEX and HECOCT coatings, which swelled considerably with an increase in wet mass of over 4400% and 2700% respectively (FIG.3F). Over the course of 7 days, HECHEX coatings slowly dissolved, while HECOCT coatings delaminated and fragmented, resulting in both coatings subsequently decreasing in both wet and dry mass (FIGs. 3F-3G). By contrast, HECMTP coatings persisted with minimal polymer resorption over the 7 days, with incubation in either PBS or 80pM H2O2 resulting in less than 12% total dry mass loss (FIGs. 3F-3G). We hypothesized that the persistence and minimal swelling of HECMTP coatings could be due to strong physical bonding between polymer chains, which is characteristic of certain cellulose ester formulations — Reexamining the FTIR for HECMTP,Attorney Docket No. 701586-000154WOPTwe noted a prominent shoulder in the spectra within the 3200-3300 cm’1region which can be attributed to enhanced intermolecular hydrogen bonding (FIG. 3H).7"7This hydrogen bonding phenomena was present only in HECMTP and was not identified in HEC, HECso, or any of the other benchmarking materials. To confirm the presence of intermolecular hydrogen bonding, we assessed whether we could re-dissolve dried HECMTP films in l,l,l,3,3,3-hexafluoro-2-propanol (HFIP), a known hydrogen bond disrupting solvent.77"77While HECMTP films swell to nearly 4000% of their original dry mass but do not dissolve after 48 hour incubation in DMSO, HFIP effectively dissolved films in their entirety over the same time course, confirming the presence of strong hydrogen bonding within the dry HECMTP material (FIGs.24A-24B).

[0402] These data show that HECMTP, when formulated as a coating, readily scavenges physiologically relevant concentrations of H2O2 with second order reaction kinetics that are dependent on both the H2O2 and thioether concentrations. Oxidation of HECMTP coatings under physiologically relevant conditions achieves the maximal wettability of the surface over the course of several days and is associated with a small increase in wet mass as the coating hydrates. Despite hydration at the coating surface, strong intermolecular hydrogen bonding between polymer chains comprising the bulk of the HECMTP coating results in minimal total swelling and negligible mass loss to ensure long-term preservation of coating integrity.

[0403] HECMTP coatings and films show oxidation-driven changes in mechanical properties: Polymer coatings or films that effectively reduce the cell-perceived mechanical stiffness of the underlying medical device may promote improved biocompatibility. As such, there has been recent interest in engineering mechanically adaptable materials which are capable of in situ softening once implanted in vivo to further improve biocompatibility outcomes.77We hypothesized that the oxidation-induced increase in surface hydrophilicity and hydration observed for HECMTP coatings under physiologically relevant conditions may also confer a concurrent reduction in mechanical stiffness, making it an effective mechanically adaptable material. To test this premise, we assessed the mechanical properties of HECMTP coatings in a number of different ways and benchmarked results against HEC and a crosslinked ethoxylated polyol (CEP)-based control (Table 5). We first conducted lap shear testing to evaluate polymer coating adhesion and interfacial shear strength in the dry state on a glass substrate. HECMTP coatings displayed a higher ultimate interfacial shear strength (2782 kPa) at failure relative to HEC (1158 kPa) and CEP (376 kPa) coating benchmarks (FIGs.4A-4B, 25A-25E). The observed adhesive strength of HECMTP on glass in the dry state makes it comparable to the performance of commonly used n-butyl-2-cyanoacrylate -based surgical glues under equivalent testing parameters — Both HECMTP and HEC coatings failed in lap shear tests by a combination of cohesive and adhesive failure whereas the CEP-based interface failed by a purely adhesive failure mechanism (FIGs. 25A-25E). The strongAttorney Docket No. 701586-000154WOPTglass substrate adhesive properties of HECMTP coatings were maintained after 7 days of incubation in PBS and we observed minimal change in coating adhesion under mild oxidizing conditions (80μM H₂O₂). However, oxidation at supraphysiological concentrations ofH2O2 (>640pM) for just one day caused HECMTP coatings to readily delaminate due to widespread conversion of polymer thioether groups to sulfoxides, which ultimately results in bulk material changes that are not seen under physiological oxidizing conditions. Next, we evaluated HECMTP films by tensile testing to assess how different oxidizing conditions alter bulk mechanical properties. HECMTP films in the dry state behaved as tough plastics with an elastic modulus of 455 MPa but softened significantly when equilibrated for 7 days in PBS such that the elastic modulus decreased by almost 3 orders of magnitude to 597 kPa and the hydrated material displayed behavior characteristic of a thermoplastic elastomer (FIGs. 4C-4D, 26A-26D). Hydration alone reduced the ultimate tensile strength of HECMTP by over an order of magnitude, from 30.1 MPa to 894 kPa. However, engineering strain at failure increased nearly three-fold, from 0.53 to 1.38 (FIGs. 26A-26D).Oxidation of HECMTP films with 80pM H2O2 for 7 days caused no significant change in the elastic modulus, ultimate tensile strength (UTS), or strain to failure compared to the PBS incubated sample, indicating that conditions sufficient to oxidize the surface of the film provoked minimal bulk material changes. Exposing HECMTP films for 4 days to supraphysiological concentrations of H2O2 (800pM) that provoked detectable bulk physical changes to films as noted above resulted in a material that was softer (Elastic modulus of 233 kPa), weaker (71% reduction in UTS), and more brittle (13% decrease in strain at failure) (FIGs.4D, 26A-26D). To assess whether physiologically relevant oxidation conditions that do not induce bulk material changes could otherwise promote changes in the surface mechanical properties of fabricated HECMTP coatings, we performed contactmode atomic force microscopy (AFM) to determine the micromechanical properties of the material interface after one day of hydration in PBS, then after 7 days of exposure to 80pM H2O2. This physiologically relevant oxidation of HECMTP coatings promoted a significant and nearly 3 -fold decrease in surface elastic modulus, reducing it from 1718kPa to 674kPa (FIG.4E).

[0404] These data show that HECMTP forms strongly adhered coatings on glass substrates and that exposure to physiologically relevant oxidizing conditions promotes an effective softening of the surface without imparting bulk changes to HECMTP coatings and films. Given that surface softening can readily occur under physiologically relevant oxidizing conditions, HECMTP can be considered a mechanically adaptable material that should soften when implanted in vivo.

[0405] HECMTP coatings can be used for optical applications: Optical devices, such as probes, microprisms, optical windows, and GRIN (Gradient-Index) lenses, incorporate transparent glass windows or fibers to image and / or optogenetically control cell functions in vivo. However, these optical devices often experience signal instability issues or chronic noise artifacts due toAttorney Docket No. 701586-000154WOPTdeleterious FBRs stimulated by device implantation — In anticipation of a potential application for HECMTP as a surface coating on implanted optical devices to improve in vivo performance, we tested the optical properties of HECMTP coatings to establish their potential compatibility with such devices. Applying HECMTP coatings to transparent glass caused no observable distortion of underlying features under brightfield microscopy (FIG. 5A), which we validated using an established, no-reference image quality assessment— to calculate image sharpness (FIG. 5B).HECMTP coatings did not attenuate transmitted light within the full spectrum tested from ultraviolet (UV) (300nm) to infrared (IR) (900nm) as assessed by UV-Vis spectroscopy (FIG.5C). Brightfield images and UV-Vis spectra measured through glass alone as well as HECMTP and oxidized HECMTP coatings demonstrated no detectable change in sharpness (FIG. 5B) or transmittance (FIG. 5C), whereas semi-opaque tape and black ink benchmarking controls effectively decreased both transmittance and sharpness in the visible wavelengths (400-700nm) by over 57% (FIGs.5B-5C).

[0406] To assess HECMTP coating compatibility with fluorescence microscopy, we first stained coronal mouse brain slices (40pm thick) using a DAPI nuclear stain (FIG. 5D) or primary antibodies for NeuN (neuronal nuclear stain) followed by secondary antibodies conjugated with different common fluorophores that have excitation and emission wavelengths spanning the visible light spectrum (FIGs.27A-27D) and imaged them using a widefield fluorescence microscope. We then calculated the relative change in image sharpness when imaging through HECMTP-coated coverslips (35pm coating thickness) compared to uncoated, glass-only coverslips (FIGs. 5D-5E, 27A-27D). Qualitative (FIGs. 5D, 27A-27D) and quantitative (FIGs. 5E) assessments both demonstrated that the HECMTP coatings caused no appreciable change in image sharpness relative to the images taken using the uncoated glass. To confirm that this result was not simply caused by limited dynamic range of the scoring algorithm, we also applied standard Gaussian smoothing to the DAPI images, which imparts an incremental and defined blurring of the labeled nuclei (FIG.5D) As expected, the application of Gaussian filters of increasing size results in significant reductions in image sharpness, contextualizing the lack of any appreciable shift in image sharpness imparted by HECMTP coatings (FIG.5E).

[0407] Next, to further assess any conferred optical effects of our biomaterial in fluorescence microscopy applications, we tested the effect of HECMTP and oxidized films of different thicknesses on the apparent distortion of sub-diffraction-sized fluorescent beads, when imaged with two-photon microscopy (2PM). Imaging objects such as these beads that are smaller in size than the diffractionlimited resolution of the microscope creates a bead image of larger apparent size, with its fluorescent intensity profile parametrized by a Gaussian distribution in three dimensions. While the ideal apparent bead diameter is equivalent to the diffraction-limited resolution of the imaging system, optical scattering can lead to larger than ideal diameters, ultimately limiting resolution ofAttorney Docket No. 701586-000154WOPTthe image. HECMTP films were created at thicknesses varying between 25 and 150pm, and then hydrated in PBS for 7 days, while oxidized films at the maximally wettable state were created by incubating dry HECMTP films in lOmL of 80 pM H2O2 in PBS for 7 days. After fluorescent beads were dried onto glass slides, the samples were covered with mounting media and then biomaterial films, press-fit onto glass coverslips, were layered over the top. Compared to a coverglass-only control, imaging through HECMTP and oxidized films visibly altered the lateral point spread function (PSF) of the beads, as shown by one-dimensional Gaussian fits of lateral fluorescent intensity profiles taken through the center of the bead (FIG. 5F). Changes in apparent resolution were derived from differences in the full width at half maximum (FWHM) for each Gaussian curve, which describes the apparent diameter of the bead. The bead FWHM detected through HECMTP films showed a small but significant increase compared to the glass only controls, and this deviation was significantly correlated with film thickness (r=0.95) (FIG. 5G). However, there was no apparent change in conferred resolution between HECMTP and oxidized films at equivalent film thicknesses (FIGs.27A-27D).

[0408] These data show that HECMTP coatings and films are suitable for diverse optical applications requiring resolution down to the micron scale. While HECMTP films ultimately impacted fluorescent image resolution on the order of nanometers, the broad array of tested optical applications suggests that sufficiently thin HECMTP coatings and films are compatible with optical devices, and that this compatibility is not affected by the oxidation-driven, hydrophobic-to-hydrophilic transition.

[0409] HECMTP films promote oxidation-responsive, controlled release of molecules:Polypropylene sulfide)-based copolymers have been used to formulate oxidation-sensitive drug delivery systems which can selectively release drug cargo via the hydrophobic-to-hydrophilic transition stimulated by sulfoxide formation — Inspired by these studies, we next tested the capacity for HECMTP films to act as oxidation-responsive controlled release systems using fluorescently detectable model small molecules and polysaccharide-based macromolecules (FIGs. 6A-6B). To characterize small molecule release from HECMTP films, we used three coumarin derivatives that have different relative hydrophobicities including 4-methylumbelliferone (4MU) (logP = 1.78), 7-Di ethylamino- 4-methylcoumarin (Cl) (logP=2.90), and coumarin 6 (C6) (logP=4.79). We observed first order release profiles for both 4MU and Cl with rate constants scaling with log P values such that there was complete recovery of loaded 4MU and Cl after 3 and 8 days respectively (FIG. 6A). Due to its limited aqueous solubility, C6 showed limited release from HECMTP films under PBS-only incubation over 14 days. The addition of 0.1% triton-XlOO surfactant into the incubation media subsequently promoted a sigmoidal pattern of release for C6, resulting in near total recovery over the subsequent 14 days (FIG.6A).Attorney Docket No. 701586-000154WOPT

[0410] To model macromolecule loading and release kinetics, FITC-dextrans with molecular weights of 10, 70, and 150kDa were incorporated into HECMTP films. These model macromolecules have matched hydrophilicities but hydrodynamic radii that are proportional to molecular weight — All model dextrans exhibited a modest initial burst release from HECMTP films when incubated in PBS which was greatest for the lOkDa FITC-dextran at 26%. By 5 days, approximately 41% of total lOkDa dextran cargo was released after which there was only minimal additional release up to 14 days. (FIG.6B). Over the same 14-day period, only -20% of the total loaded 70 and 150kDa FITC-dextrans were released from HECMTP films showing minimal but steady release after 7 days. To test for oxidation-stimulated release of the residual dextran cargo in these HECMTP films, we exposed films to 80pM H2O2 for 7 days followed by 320pM H2O2 for an additional 7 days. The 80pM H2O2 media promoted no significant increase in the rate of dextran release relative to the preceding 7 days in PBS only (FIG.6C). However, at 320pM H2O2 there was a significant near 3-fold increase in the release rates for all dextrans (FIG.6C).

[0411] To further dissect the oxidation-sensitive release properties of HECMTP films, we studied the initial release profiles of freshly prepared films loaded with 70kDa FITC-dextran under 80pM and 800pM H2O2 oxidizing conditions, which we established induces surface and bulk hydrating effects respectively. FITC-dextran released from films exposed to physiologically relevant 80pM H2O2 showed a near constant, zeroth order release profile following the first day burst which is consistent with molecular release being mediated by material surface hydrating effects (FIGs.6D-6E, 28). Under these oxidizing conditions, approximately 37% of loaded cargo had been released after 20 days, which was nearly 1.4x the total amount that was released from PBS-only incubated samples during the same timeframe. Incubating films in 800pM H2O2 resulted in an additional and significant increase in both the total amount and rate of FITC-dextran release, with over 60% of FITC-dextran recovered after just 10 days. Under these supraphysiological oxidizing conditions, the molecular release profile showed first order release kinetics, consistent with bulk-hydration of the material (FIGs.6D-6E, 28). Next, to test the capacity for HECMTP films to promote on-demand molecular release upon H2O2 exposure, we introduced intermittent 24-hour pulses of 800pM H2O2 (FIG. 6F), 320pM H2O2 (FIG.6G), or 80pM H2O2 (FIG. 6G), to dextran-loaded films after 2, 5, and 8 days of incubation in PBS-only solutions. There was a significant spike in dextran release in response to the three intermittent exposures to H2O2 and release was attenuated upon removal of the oxidizing stimulus (FIGs. 6F-6H). These bursts in dextran release scaled linearly with the concentration of applied H2O2, further demonstrating that HECMTP films provide oxidation-responsive release. Since tissue environments at chronically implanted medical devices or wounds can experience local fluctuations in ROS that can be provoked by new inj uries or chronic infections,Attorney Docket No. 701586-000154WOPTthe on-demand release properties of HECMTP films may be useful for dynamically delivering drugs to regulate such responses.

[0412] HECMTP films are nonfouling substrates that persist in vivo with minimal foreign body response for up to 4 weeks. To test the cytocompatibility of HECMTP coatings, we first cultured quiescent mouse astrocytes on surfaces coated with HEC, HECMTP, or HECMTP oxidized to its maximal wettability state with 320pM H2O2 incubation. Astrocytes are a principal cell type involved in the central nervous system foreign body response (FBR) to biomaterials in vivo, and therefore represent an appropriate cell type for initial in vitro evaluations — Astrocytes plated on either of the three experimental coatings showed no significant decrease in cell viability relative to tissue culture plastic controls (FIG. 7A). Next, we characterized astrocyte adhesion to coatings made from HECMTP and HECMTP pre-treated with incrementally increasing concentrations of H2O2 spanning physiological and supraphysiological values. While cultured astrocytes completely adhered and readily spread onto tissue culture plastic, astrocyte adhesion was reduced by more than 57% on HECMTP coatings, with cells coalescing into discrete multi-cellular aggregates that were approximately 100 pm in diameter (FIGs. 7B-7C). Oxidized HECMTP coatings exposed to at least 20pM H2O2 showed further attenuated astrocyte adhesion with less than 5% total cell fouling detected across all oxidized HECMTP conditions. Such minimal cell adhesion was equivalent to that noted on HEC-only coated substrates and is consistent with results observed for other sulfoxide based materials— (FIGs. 7B-7C). The attenuated cell fouling results were likely conferred by minimal protein adsorption to HECMTP-based substrates, since HECMTP and oxidized HECMTP fdms showed a nearly 94% reduction in total albumin adsorption compared to a gelatin benchmarking surface by in vitro testing (FIGs.29A-29C).

[0413] Having established that HECMTP coatings are cytocompatible and minimally cell and protein fouling in vitro, we next assessed the stability and FBRs of HECMTP fdms in vivo. Before HECMTP fdms could be implanted in vivo, we first tested their resilience to standard sterilization methods including autoclaving and soaking in alcohol solutions. We identified minimal changes in HECMTP dry mass across all conditions (<1%), but soaking HECMTP coatings in 70% IPA overnight led to a 5-10% decrease in optical transmittance across the 300-900nm spectrum. Based on these findings, autoclaving was deemed to be the most appropriate sterilization method for HECMTP coatings and films (FIGs. 30A-30B). To evaluate the biocompatibility and FBR to the HECMTP material, we prepared free-standing 3mm diameter HECMTP films at ~115pm thickness using an optimized fabrication method (FIG. 21). HECMTP films were sterilized by autoclave and hydrated in sterile PBS for one day before use. Films of HECHEX, HECOCT, and regenerated cellulose (RC) served as benchmarking controls for this in vivo FBR analysis. RC films demonstrated limited swelling (144%) after one day and negligible degradation after 7 days, making the physicalAttorney Docket No. 701586-000154WOPTproperties of RC suitable for comparison with HECMTP (FIGS. 31A-31B). Despite the noted swelling and degradation limitations of the HECHEX and HECOCT materials (FIGs. 31A-31B) we proceeded with evaluating the FBRs of all four materials (HECMTP, HECHEX, HECOCT, and RC) in vivo in mice.

[0414] For FBR evaluations, we implanted films subcutaneously in pro-fibrotic, C57BL / 6 mice by placing hydrated films into pockets made bilaterally in the fascia tissue plane immediately below the panniculus camosus (PC) muscle layer of the skin in regions on the back just above the hindlimbs. After 4 weeks, we perfused mice and excised skin encompassing the implant site for gross and histological analysis (FIGs. 7D-7E, 32). On gross inspection we noted persistence of all implanted HECMTP films at 4 weeks with minimal change in size, morphology, or transparency. For some, but not all, HECMTP treated mice, films readily separated from the subcutaneous implant site on dissection due to sparse peri-implant tissue around the film and we were able retrieve these samples as intact films (FIGs. 7F, 32). Neither HECHEX or HECOCT films could be identified on gross inspection, however obvious localized regions of differentially-colored scar tissue remained at the implant sites for mice receiving these materials. Histology of explanted films by hematoxylin and eosin (H& E) and Masson’s Trichrome (MT) staining revealed thin and loose peri -implant tissue around HECMTP films with minimal numbers of persisting immune cells at the film surface and no cell infiltration into the bulk of the material (FIGs. 7D-7E, 33). By contrast, both HECHEX and HECOCT films showed significant immune cell infiltrates and collagen-rich fibrosis that penetrated throughout pockets of residual polymer material. HECHEX promoted a more severe immune response compared to all other tested materials with immune cells having larger nuclei as well as cytoplasms that were more basophilic (FIGs. 7D-7E, 33). There was a greater extent of immune cell infiltration and fibrosis with organized collagen fibers permeating throughout the implant site in animals receiving HECHEX compared to all other groups. The immune response to HECOCT showed notably paler immune cells with more condensed nuclei and large, clear cytoplasmic vacuoles consistent with foamy macrophages, which was unique to this material. Meanwhile, examination of peri-implant tissue at RC films revealed a fibrotic capsule that had a similar abundance of recruited immune cells as HECMTP both within the fibrotic tissue layers above and below the RC film as well as deposited along the material-tissue interface (FIGs.7D-8E, 33, 34A-34B). Quantification of peri-implant fibrotic capsule thickness inclusive of the superficial and deep layers measured from the end of the PC muscle layer verified that HECMTP films were not significantly different from RC, a widely used, biocompatible biomaterial, and promoted a significantly less severe FBR compared to both HECHEX and HECOCT films (FIG. 7G). Further analysis of the deep fibrotic capsule layer and dense collagen layer around HECMTP and RC films revealed no significant differences between the two biomaterials (FIGs. 7H, 34A-34C). HECMTPAttorney Docket No. 701586-000154WOPTfilms retrieved from mice after 4 weeks had a small, but detectable, increase in hydrated mass compared to pre-implant films and chemical characterization of retrieved films by FTIR showed changes in the hydroxyl and thiocarbamoyl stretch regions consistent with oxidation-induced sulfoxide conversion of some of the thioether groups along the HECMTP polymer chain (FIG. 71).

[0415] These data show that HECMTP films are cytocompatible and form non-fouling interfaces upon exposure to physiologically relevant oxidizing conditions. HECMTP is non-resorbable and persists for up to 4 weeks in vivo with minimal induced FBR or physical property changes, which was uniquely conferred by its functionalization with MTP groups. Sulfoxide conversion of the pendant thioether groups on the polymer chains in explanted films demonstrated that HECMTP can undergo the hydrophobic-to-hydrophilic transition in vivo under physiological conditions and serves as proof-of-principle evidence that justifies the future exploration of HECMTP for applications as an oxidation-responsive biomaterial. Performance longevity of chronically implanted medical devices remains a significant challenge. Hydrophilic polymer coatings or films are a potential way to prevent premature device failure by improving overall biocompatibility. However, issues such as swelling, delamination, and manufacturing scale-up have hampered the effective incorporation of existing coating and film technologies into medical devices.22-41Here, we addressed these issues by functionalizing a readily-sourced and inexpensive cellulose derivative, HEC, with thioether groups via a one-pot, isothiocyanate-based reaction to generate a new, oxidation-responsive biomaterial, HECMTP. HECMTP can be fabricated into stable, minimally swelling coatings or films that undergo oxidation-driven hydrophobic-to-hydrophilic transitions under physiological conditions to generate non-fouling and mechanically adaptable substrates. Our findings demonstrate proof-of-principle that HECMTP is a biocompatible and non-resorbable biomaterial in vivo and has implications for: 1) extending the functionality of cellulose-based material coatings and films; 2) biomaterial coatings on chronically implanted medical devices; 3) incorporating HECMTP coatings / films onto optical devices, and 4) using HECMTP for acute inflammation resolution to improve medical device biocompatibility.

[0416] Cellulose is an abundant, inexpensive, and sustainable polymer feedstock that has provided significant societal value over the past century.42122Cellulose-based materials continue to have broad impact across many industrial applications because of their versatile physical and chemical properties which can be tuned by modifications to polymer structure including the degree and type of chemical substitutions on the repeating anhydroglucose unit — Here, we add to the growing list of permitted chemical modifications to cellulose materials by developing HECMTP, a new thioether functionalized cellulose. HECMTP represents an important advance in cellulose-based materials as it can be directed to behave like either a cellulose ester or a hydrophilic cellulose derivative under different conditions, affording unique properties and processing capabilities.Attorney Docket No. 701586-000154WOPTCellulose esters are the predominant class of cellulose materials produced commercially in part because they can be dissolved and easily processed in organic solvents. Here, we show that HECMTP can be readily dissolved in DMSO and blends of common green solvents enabling a similar level of processability that is critical to fabricating commercially viable coatings and films. However, unlike cellulose esters which are moderately hydrophobic, HECMTP can be facilely transformed into a hydrophilic polymer by a simple, oxidation-driven conversion of pendant thioether groups to sulfoxides. While coatings made from other hydrophilic cellulose derivatives suffer from swelling and delamination issues,— the controlled hydrophobic-to-hydrophilic transition of HECMTP that occurs at the surface of the material under physiologically-relevant oxidizing conditions enables the generation of a highly wettable surface without causing bulk material changes that compromise coating integrity or its adhesion to the underlying substrate. Further work will be required to optimize HECMTP solution parameters, such as polymer concentration and solvent composition, to address the protracted time required for fdm formation, which is a current limitation of this system, due to the low volatility of the DMSO-only solvent system. In addition to increased manufacturing speed, HECMTP formulation innovations would allow us to incorporate other coating techniques, such as layer-by-layer assembly or spin coating, to generate thinner HECMTP coatings with a more uniform surface topography than what was achieved here. Given the modular nature of the thioether functionalization method, important next steps will be to extend our approach to other cellulose derivatives, or to different molecular weight HEC, to tune chemical functionality and / or solution viscosity in order to derive coatings and films with adjustable physical and mechanical properties. Since thioether groups are susceptible to modification by alkylation reactions, the HECMTP template could also be used to generate other functional materials in future work. For example, reacting HECMTP substrates with alkyl halides would likely be an effective way to convert thioethers to sulfonium groups and generate potent antimicrobial surfaces.59Also, modification of HECMTP with haloacetic acids could be used to create new zwitterionic substrates that would likely lead to further improvements in the cell and protein non-fouling properties.13,59

[0417] Independent of device geometry factors, the main areas where biomaterials engineering can improve long-term performance of chronically implanted medical devices lies in the optimization of surface chemistry, surface topography, and mechanical properties of the device at the device-tissue interface. Biomaterial coatings afford a way to control these surface properties. Ideally, coating technologies must be scalable, readily processable, evoke a minimal foreign body response, be capable of limiting the extent of tissue damage caused by device implantation, exhibit controlled or minimal degradation, and be suitably compatible with primary device functions. Commonly employed biomaterial coatings have also afforded additive functions such as antiAttorney Docket No. 701586-000154WOPTfouling, controlled degradation and drug release, enhanced wear resistance, and electrical conduction or insulation. However, most common synthetic polymers can only permit a few of these functions, and ultimately require concessions to be made to certain other properties. For example, polyethylene glycol (PEG)13’14and zwitterionic polymers (e.g. polycarboxybetaine, polysulfobetaine)13,15’16have demonstrated excellent protein and cell anti-fouling, but suffer from swelling, delamination, and fabrication challenges.32 36Materials designed to exhibit controlled degr...

Claims

Attorney Docket No. 701586-000154WOPTCLAIMSWhat is claimed is:

1. A thioether-functionalized cellulose polymer, comprising a cellulose backbone of repeating anhydroglucose units and thioether substituents covalently attached to at least a portion of the hydroxyl groups of said repeating anhydroglucose units.

2. The polymer of claim 1, wherein the polymer is hydroxy ethyl cellulose (HEC) or methyl cellulose (MC) or Hydroxy propyl methylcellulose (HPMC).

3. The polymer of any one of claims 1-2, wherein the polymer is hydroxyethyl cellulose.

4. The polymer of any one of claims 1-3, wherein the polymer is oxidation-responsive.

5. The polymer of any one of claims 1-4, wherein the polymer undergoes a hydrophobic-to- hydrophilic transition upon exposure to a reactive oxygen species (ROS).

6. The polymer of any one of claims 1 -5, wherein at least a portion of the thioether substituents are oxidized to sulfoxide or sulfone.

7. The polymer of any one of claims 1 -6, wherein at least a portion of the thioether substituents are alkylated to sulfonium ions.

8. The polymer of any of claims 1-7, wherein at least a portion of the thioether substituents are zwitterionic.

9. The polymer of any one of claims 1-8, wherein at least 2.5 mol % of the hydroxyl groups in the polymer are modified with the thioether substituent.

10. The polymer of any one of claims 1-9, wherein from about 2.5 to about 95 mol% of the hydroxyl groups in the polymer are modified with the thioether substituent.

11. The polymer of any one of claims 1-10, wherein 5-30 mol% of the hydroxyl groups in the polymer are modified with the thioether substituent.Attorney Docket No. 701586-000154WOPT12. The polymer of any one of claims 1-11, wherein the polymer comprises an average of about 0.5 to 2 thioether groups per anhydroglucose repeat unit.

13. The polymer of any one of claims 1-12, wherein each anhydroglucose repeat unit comprises about 0.63 thioether groups.

14. The polymer of any one of claims 1-13, wherein the polymer comprises from about 10 to about 100,000 anhydroglucose repeat units.

15. The polymer of any one of claims 1-14, wherein the polymer has a molecular weight (MW) of from about 0.5kDa to about 1,000 kDa.

16. The polymer of any one of claims 1-15, wherein the polymer has a molecular weight (MW) of from about 300 kDa to about 500 kDa.

17. The polymer of any one of claims 1-16, wherein the polymer has a polymer dispersion Index (PDI) of from about 0.25 to about 5.

18. The polymer of any one of claims 1-17, wherein polymer is transparent or semi-transparent (e.g., the polymer has a level of transmittance greater than 50%, such as a level of transmittance greater than 90% at a wavelength from about 300 nm to about 900 nm.

19. The polymer of any one of claims 1-18, wherein the polymer is thermally stable.

20. The polymer of any one of claims 1-19, wherein the polymer is hydrophobic.

21. The polymer of any one of claims 1-20, wherein the polymer has a water contact angle of about 50 degrees or higher.

22. The polymer of any one of claims 1-21, wherein the polymer is hydrophilic.

23. The polymer of any one of claims 1-19 or 22, wherein the polymer has a water contact angle of about 40 degrees or lower.

24. The polymer of any one of claims 1-23, wherein the polymer is biocompatible.Attorney Docket No. 701586-000154WOPT25. The polymer of any one of claims 1-24, wherein the polymer is non-biodegradable or non- resorbable.

26. The polymer of any one of claims 1-24, wherein the polymer is biodegradable.

27. The polymer of any one of claims 1-26, wherein the polymer is non-immunogenic.

28. The polymer of any one of claims 1-27, wherein the polymer is antifouling.

29. The polymer of any one of claims 1-28, wherein the polymer is a copolymer.

30. The polymer of any one of claims 1-29, wherein the polymer is a block polymer.

31. A composition comprising a thioether-functionalized cellulose polymer of any one of claims 1-30.

32. The composition of claim 31, wherein the composition further comprises a solvent.

33. The composition of claim 32, wherein the solvent is a polar solvent.

34. The composition of claim 32, wherein the solvent is a non-polar solvent.

35. The composition of claim 32, wherein the solvent is a mixture of a polar solvent and a nonpolar solvent.

36. The composition of claim 32, wherein solvent is a protic solvent.

37. The composition of claim 32, wherein the solvent is an aprotic solvent.

38. The composition of claim 32, wherein the solvent is an organic solvent.

39. The composition of claim 32, wherein the solvent is an aqueous solvent.

40. The composition of claim 32, wherein the solvent is a green solvent.Attorney Docket No. 701586-000154WOPT41. The composition of claim 32, wherein the solvent is a halogenated solvent.

42. The composition of any one of claims 31-41, wherein the polymer is present at a concentration of from about 0.01 to about 90% w / w or w / v of the total composition.

43. The composition of any one of claims 31-42, wherein the polymer is present at a concentration of from about 0.1 to about 50% w / w or w / v of the total composition.

44. The composition of any one of claims 31-43, wherein the polymer is present at a concentration of from about 0.5 to about 7.5% w / w or w / v of the total composition.

45. The composition of any one of claims 31-44, wherein the composition has a viscosity of from about 0.01 to about 250 Pa s.

46. The composition of any one of claims 31-45, further comprising a therapeutic agent.

47. A film comprising a thioether-functionalized cellulose polymer of any one of claims 1-30.

48. The film of claim 47, wherein the film has a thickness of from about 1 pm to about 150 pm.

49. The film of any one of claims 47-48, wherein the film has an average surface roughness from about 5 nm to about 50 nm.

50. The film of any one of claims 47-49, wherein the film is antifouling.

51. The film of any one of claims 47-50, wherein the film undergoes a hydrophobic-to- hydrophilic transition at a surface region with minimal bulk swelling, e.g., under physiological conditions.

52. The film of any one of claims 47-51, wherein the film has a higher ultimate interfacial shear strength at failure relative to a film of a same cellulose polymer lacking the thioether substituents.Attorney Docket No. 701586-000154WOPT53. The film of any one of claims 47-52, wherein the film has a ultimate interfacial shear strength at failure is from 2000 kPa to 3500 kPa.

54. The film of any one of claims 47-53, wherein the film has an elastic modulus of from about 200 MPa to about 500MPa in a dry state.

55. The film of any one of claims 47-54, wherein the film has an ultimate tensile strength of from about 20 MPa to about 50 MPa in a dry state.

56. The film of any one of claims 47-55, wherein the film has an elastic modulus of from about 500 MPa to about 750 MPa in a hydrated state.

57. The film of any one of claims 47-56, wherein the film has an ultimate tensile strength of from about 700 MPa to about 1,100 MPa in a hydrated state.

58. The film of any one of claims 47-57, wherein the film has a surface elastic modulus of from about 200 kPa to about 700 kPa in an oxidized state.

59. The film of any one of claims 47-58, wherein the film is transparent or semi-transparent (e.g., the film has a level of transmittance greater than 50%, such as a level of transmittance greater than 90% at a wavelength from about 300 nm to about 900 nm.

60. The film of any one of claims 47-59, wherein the film has minimal fluorescent scattering.

61. The film of any one of claims 47-60, wherein the film further comprises a therapeutic agent.

62. The film of claim 61, wherein the therapeutic agent is released from the film when the film undergoes a hydrophobic-to-hydrophilic transition.

63. The film of claims 61 or 62, wherein the therapeutic agent is released from the film when the film is exposed to a reactive oxygen species.

64. The film of claims 62 or 63, wherein said release of the therapeutic agent from the film is a controlled release.Attorney Docket No. 701586-000154WOPT65. The film of any one of claims 62-64, wherein said release of the therapeutic agent from the film is a sustained release.

66. The film of any one of claims 47-65, wherein the film is hydrophobic.

67. The film of any one of claims 47-66, wherein the film has a water contact angle of about 50 degrees or higher.

68. The film of any one of claims 47-65, wherein the film is hydrophilic.

69. film of any one of claims 47-65 or 68, wherein the film has a water contact angle of about 40 degrees or lower.

70. The film of any one of claims 47-69, wherein the film is biocompatible.

71. The film of any one of claims 47-70, wherein the film is non-biodegradable or non- resorbable.

72. The film of any one of claims 47-70, wherein the film is biodegradable.

73. The film of any one of claims 47-72 wherein the film is non-immunogenic.

74. The film of any one of claims 47-73, wherein the film is antifouling.

75. The film of any one of claims 47-74, wherein the film comprises two or more layers to form a multi-layered film.

76. The film of claim 75, wherein a first layer comprises a first polymer selected from polymers of any of claims 1-30 and a second layer comprises a second polymer that is different from the first polymer.

77. The film of any one of claims 47-75, wherein the film is on a surface of a substrate.

78. The film of claim 75, wherein the substrate is a medical device.Attorney Docket No. 701586-000154WOPT79. A fiber comprising a thioether-functionalized polymer of any one of claims 1-30.

80. The fiber of claim 79, wherein the fiber has a diameter between about 1 nm and 5 mm.

81. A particle comprising a thioether-functionalized cellulose polymer of any one of claims 1 - 30.

82. The particle of claim 81, wherein the particle is a microparticle or a nanoparticle.

83. The particle of claims 81 or 82, wherein the thioether-functionalized cellulose polymer is at a surface of the particle.

84. The particle of claims 82 or 83, wherein the thioether-functionalized cellulose polymer is in an interior of the particle.

85. The particle of any one of claims 81-84, wherein the particle further comprises a therapeutic agent.

86. The particle of claim 85, wherein the therapeutic agent is released from the particle when the particle undergoes a hydrophobic-to-hydrophilic transition.

87. The particle of claims 85 or 86, wherein the therapeutic agent is released from the film when the particle is exposed to a reactive oxygen species.

88. The particle of claims 86 or 87, wherein said release of the therapeutic agent from the particle is a controlled release.

89. The particle of any one of claims 86-88, wherein said release of the therapeutic agent from the particle is a sustained release.

90. The particle of any one of claims 82-89, wherein the particle has a diameter of between about 1 nm and about 2 microns.Attorney Docket No. 701586-000154WOPT91. A substrate comprising a coating or film on at least a portion of a surface of the substrate, wherein the coating or film comprises a thioether-functionalized cellulose polymer of any one of claims 1-30.

92. The substrate of claim 91, wherein the substrate is a medical device.

93. The substrate of claim 92, wherein the medical device is a catheter, a pacemaker, a drug infusion pump, an implanted optical system, a stent, a vascular graft, a neurostimulator, a cochlear implant, an orthopedic implant, a cardiac lead, a biosensor, an artificial heart valve, an implantable glucose monitor, or an implantable drug depot.

94. The substrate of any one of claims 91-93, wherein the coating or film has a thickness from about 0.1 pm to about 150 pm.

95. The substrate of any one of claims 91-94, wherein the coating or film has a thickness from about 1 pm to about 75 pm.

96. The substrate of any one of claims 91-95, wherein the coating or film has an average surface roughness from about 5 nm to about 50 nm.

97. The substrate of any one of claims 91-96, wherein the coating or film comprises a therapeutic agent.

98. The substrate of any one of claims 91-97, wherein the coating or film the film is hydrophobic.

99. The substrate of any one of claims 91-98, wherein the coating or film has a water contact angle of about 50 degrees or higher.

100. The substrate of any one of claims 91-97, wherein the coating or film is hydrophilic.

101. The substrate of any one of claims 91 -97 or 100, wherein the film has a water contact angle of about 40 degrees or lower.

102. The substrate of any one of claims 91-101, wherein the coating or film is biocompatible.Attorney Docket No. 701586-000154WOPT103. The substrate of any one of claims 91-102, wherein the coating or film is non-biodegradable or non-resorbable.

104. The substrate of any one of claims 91-103, wherein the coating or film is non- immunogenic.

105. The substrate of any one of claims 91-104, wherein the coating or film is antifouling.

106. A drug-delivery article comprising a thioether-functionalized cellulose polymer of any one of claims 1-30 and a therapeutic agent.

107. The drug delivery article of claim 106, wherein the drug delivery article is in the form of a film, a particle, a mesh, a fiber, a gel, a hydrogel, a foam, a mesh, a mat, a non-woven mat, or any combinations thereof.

108. The drug delivery article of claims 106 or 107, wherein the drug delivery article is multilayered.

109. The drug delivery article of any one of claims 106-108, wherein the drug delivery article comprises a coating or film on a surface of substrate, and wherein the coating or film comprises the thioether-functionalized cellulose polymer.

110. The drug delivery article of any one of claims 106-109, wherein the thioether- functionalized cellulose polymer and the therapeutic agent are in a mixture, e.g., homogenous mixture.

111. The drug delivery article of any one of claims 106-109, wherein the thioether- functionalized cellulose polymer and the therapeutic agent are present separately in the drug delivery article.

112. The drug delivery article of any one of claims 106-111, wherein the drug-delivery device is cylindrical, circular or spherical, rectangular, cubic, polyhedron, prism, disc, other geometric shape, or any combinations thereof.Attorney Docket No. 701586-000154WOPT113. The drug-delivery device of any of claims 106-112, wherein the drug delivery article is in form of an implant or an implantable device.

114. A method for controlling the release of a therapeutic agent, the method comprising: (a) providing a drug-delivery article of any of claims 106-113; and (b) inducing a hydrophobic- to-hydrophilic transition in the thioether functionalized cellulose polymer.

115. A method of forming a coating on a surface of a substrate, the method comprising applying a thioether-functionalized cellulose polymer of any one of claims 1-30 to at least a portion of a surface of the substrate.

116. The method of claim 115, wherein the step of coating at least a portion of a surface of the substrate comprises dip coating, spray coating, spin coating, drop casting, roll coating, or any combination thereof.

117. The method of claims 115 or 116, wherein the substrate is a medical device.

118. The method of any one of claims 115-117, wherein the polymer is applied as a solution.

119. The method of claim 118, further comprising a step of removing a solvent from the solution comprising the polymer after forming the coating or fdm.

120. The method of claim 115, wherein the method comprises applying a solution comprising the polymer to a mold and removing a solvent from the solution after applying to the mold.

121. The method of claims 119 or 120, wherein step of removing the solvent comprises temperature and / or pressure-controlled vaporization of the solvent.

122. The method of any one of claims 115-121, further comprising a step of drying the substrate after the step of applying the polymer.

123. The method of claim 122, wherein said drying step is under vacuum.

124. The method of any claims 122 or 123, wherein said drying step is at a temperature higher than room temperature.Attorney Docket No. 701586-000154WOPT125. The method of any one of claims 115-124, wherein the coating or film comprises a therapeutic agent.

126. A method for preparing a thioether-functionalized cellulose polymer, the method comprising reacting a cellulose polymer with a thioether-functionalizing reagent.

127. The method of claim 126, wherein the thioether-functionalizing reagent is an isothiocyanate-based thioether-functionalizing reagent.

128. The method of claims 126 or 127, wherein the thioether-functionalizing reagent is 3- (methylthio)propyl isothiocyanate.

129. The method of any one of claims 126-128, wherein the polymer is hydroxyethyl cellulose (HEC) or methyl cellulose (MC) or Hydroxy propyl methylcellulose (HPMC).

130. The method of any one of claims 126-129, wherein the polymer is hydroxyethyl cellulose.

131. The method of any one of claims 126-130, wherein the cellulose polymer is hydroxy ethyl cellulose.

132. The method of any one of claims 126-131, wherein the thioether-functionalized cellulose polymer is a polymer of any one of claims 1-30.

133. A polymeric mesh, foam, or hydrogel comprising a thioether-functionalized cellulose polymer of any of claims 1-30.

Images