Fluorine-free lubricant-infused pva

Abstract

Highly flexible, lubricant-infused silane-crosslinked polyvinyl alcohol (PVA) films as well as methods of making and using such films. Lubricant-infused properties are introduced throughout the entire volume of the film. An organosilane crosslinking agent, such as an alkyl silane crosslinking agent, and more specifically propyl trichlorosilane (nPTCS) is used to generate a crosslinked PVA film on a substate or as a free-standing film or membrane. The crosslinked film or membrane is infused with a compatible lubricant, such as silicone oil, to produce a lubricant-infused crosslinked PVA film. Stable lubricant-infused films are provided that exhibit significantly enhanced antibacterial and antithrombotic properties compared to control PVA film samples. Such films can be formed on any surface that comes in contact with a biological fluid to provide protection from fouling by that biological fluid. Articles provided with such films include, for example, fluid conduits, seals, optical articles and medical devices inserted and retained in the body.

Description

FLUORINE-FREE LUBRICANT-INFUSED PVACROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of U.S. provisional application 63 / 712,534, filed October 28, 2024, which is incorporated by reference herein in its entirety.BACKGROUND

[0002] Devices intended for use in contact with biofluids can suffer from biofouling, leading to thrombus formation and bacterial biofilm buildup, impairing device function, and pose health risks. Polymers are widely used in clinical applications in which biofluids are contacted. Polymeric and other materials used in such devices and applications should avoid blood clot formation, and biofouling. A variety of surface coatings that can prevent unwanted adhesion with bio-compatible materials have been investigated. Traditional antifouling methods, like use of hydrophilic polymers or heparin coatings, often suffer from instability and reduced effectiveness over time. Certain coatings, including those incorporating bioactive molecules, may degrade over time and pose potential health risks, such as an elevated risk of bleeding.

[0003] There has been a growing interest in lubricant-infused surfaces (LIS) as an approach to mitigate non-specific adhesion in such devices and applications. LIS can exhibit superior properties compared to conventional techniques and can demonstrated prolonged stability and broad-spectrum repellency with resistance to various contaminants, including blood proteins, cells, bacteria, and fatty molecules. Current LIS technologies typically involve complex, multi-step processes that restrict their application to surface layers, potentially compromising performance under mechanical stress. This invention relates to a novel category of flexible lubricant-infused polyvinyl alcohol (PVA) films or membranes. These films are fabricated through the crosslinking of the PVA polymer chain using an organosilane crosslinking agent, such as an alkyl trichlorosilane or more specifically n-propyl trichlorosilane (nPTCS), and subsequent surface modification involving silicone oil infusion as a lubricant layer. The crosslinking of PVA by the organosilane significantly decreases degradation rate, and enhances flexibility, and fatigue resistance properties of the resulting PVA film or membrane. Films obtained exhibit low sliding angles and prolonged clotting times for blood and plasma when contrasted with control PVA samples. Additionally, films obtained exhibit significant resistance to blood and bacterial adhesion, making them useful for diverse applications in blood-contacting medical contexts.

[0004] Devices having surfaces that contact biofluids and medical implants are highly prone to fouling. Blood-contacting devices in particular are prone to thrombogenic fouling, resulting from blood protein and platelet adhesion [1 ,2], and pathogenic biofouling caused by bacterial adhesion and biofilm formation. These complications can impair device performance, prolong hospital stays, andlead to life-threatening events such as systemic infection or embolisms [3,4], Moreover, prophylactic medical interventions aimed to mitigate these complications can lead to additional issues such as excessive bleeding caused by anticoagulant medications or the emergence of antimicrobial-resistant bacteria due to antibiotic use, a crisis that poses a worldwide public health threat [5,6],

[0005] The surface properties of a biomaterial substrate (e.g., micro-nano structures, roughness, wettability) significantly influence the adhesion, spreading, and interaction of biomolecules and cells with the biointerface with the substrate, thereby playing an important role in determining the effectiveness of the substrate in preventing / enhancing biointeractions [7,8], Several surface coatings have been investigated to either passively or actively prevent fouling on biomaterials [9-13], For instance, sulfonated chitosan possesses a highly negative charge and can mimic the structure of heparin, effectively preventing blood protein adhesion [9], Polyethylene oxide) (PEO)

[0014] and polyethylene glycol) (PEG) [15,16] create a protective hydration layer between the underlying substrate and the biological environment

[0017] , Additionally, proteins and antithrombotic agents such as heparin can disrupt the coagulation cascade and actively prevent thrombogenic fouling [18-22], Despite the improved antifouling properties of biointerfaces coated with these technologies, they face several limitations, which include the transient and unstable nature of the active surface coatings, which can desorb over time, limiting their applicability to single-use devices for short treatment applications

[0023] , Notably, the initial clinical benefits observed in heparin-coated devices are often not sustained due to the inability to maintain heparin surface activity caused by enzymatic or chemical degradation

[0067] , Polymers, such as PEO and PEG, may exhibit polymer chain degradation through oxidation reactions in vivo, affecting their clinical use. Surfaces modified with PEG were reported to exhibit decreased protein adsorption that resulted in a prolonged coagulation time and reduced platelet activation compared to a bare titanium oxide substrate

[0022] , However, the clinical use of PEG- modified materials remains limited as their protein resistance is less effective in vivo than has been reported in vitro

[0017] , Additionally, the high cost of purification of heparin and other anti-thrombotic agents hinders their widespread adoption [9], Further, in any of these approaches, any surface coating defects may serve as pinning points for non-specific adhesion, leading to stable attachment and biofouling over time. Despite their intended effects, such coatings often prove ineffective in preventing non-specific adhesion as evidenced by observations of bacterial and protein attachment.

[0006] LIS which use an immiscible and nonreactive lubricant layer to shield the substrate from contaminants, have emerged as highly effective coatings for preventing biointerface-associated fouling [24-27], These surfaces have exhibited long-term stability and repellency towards a range of aqueous and biological liquids including water, blood, and plasma [28,29], demonstrating antiwetting

[0030] , antithrombotic [31 ,32], and antibacterial

[0033] properties. Additionally, the lubricant layer prevents droplet nucleation within the texture, ensuring continued functionality even in humid conditions

[0027] , LIS coatings have been applied to a variety of different polymeric materials, including synthetic polymers such as polyvinyl alcohol (P A) [34,35], polyethylene terephthalates (PET)

[0036] ,polytetrafluoroethylene (PTEF)

[0033] , polydimethylsiloxane (PDMS)

[0030] , and natural polymers, such as bacterial nanocellulose (BNC)

[0037] and chitosan [2],

[0007] To achieve a highly stable LIS on these materials, it is important to create a robust chemical affinity between the solid flat, or rough / porous substrate and the lubricating fluid. To establish this interaction, previous studies have employed modification techniques such as chemical vapor deposition (CVD) [32,38] and liquid-phase deposition (LPD)

[0031] to coat the surface using different silane molecules, including propyltrichlorosilane

[0038] , aminopropyltriethoxysilane, polytrifluoropropylmethylsiloxan

[0039] , These complicated and multi-step synthesis processes typically result in a thin surface coating on the substrate, which prevents the lubricant layer from being applied to the entire bulk material[38,40]. This leads to the formation of biphasic biointerfaces, where the surface and bulk possess different properties that can affect their functionality and performance in dynamic biological environments. Specifically, for flexible biomaterials that may undergo stretching and various mechanical loads, the confinement of the lubricant-infused coating to the surface can impact the overall performance of the biointerface due to the lack of a homogeneous layer within the bulk material

[0037] ,

[0008] Medical-grade lubricants that incorporate fluorine, such as perfluorodecalin, are have been reported for making LIS [32,33,68], However, in view of the challenges posed by depletion, and high evaporation rates of these lubricants [69,70] and the known environmental and health risks of fluorocarbons [86, 87], fluorine-free silanes

[0038] and high-viscosity medical-grade silicone oils have been studied as alternatives [71-73], These studies have reported that silicone oil is nontoxic and has great potential to create a stable, extremely slippery interface that exhibits exceptionally low protein and bacterial adhesion and prevents biofilm formation.

[0009] Creation of robust LIS involves impregnation into micro / nanostructure surfaces with suitable surface energy which facilitates the lubricant spreading and retention / blocking via van der Waals and capillary forces to form a stable immiscible overlayer [25,38,73,74], Additionally, to maintain a long-term and self-healing lubricant layer, the establishment of a strong chemical affinity between the solid and the lubricating fluid is believed important. To generate this affinity, previous studies largely used additive approaches, such as electrochemical deposition

[0075] , chemical vapor deposition (CVD) [32,38], and liquid-phase deposition (LPD)

[0031] , Such approaches were reported to generate fluorine-based or silicone-based coatings on substrates to achieve the chemical affinity for fluorine-based and silicon-based lubricants, respectively. However, these approaches make the operation process complex, often requiring a complicated, multi-step synthesis process that cannot be completed without significant attention to detail.

[0010] Among the polymers, polyvinyl alcohol (PVA) has been widely used for blood- connected medical applications [76-78], PVA is a synthetic polymer obtained through the partial or complete hydroxylation of polyvinyl acetate

[0079] , PVA films have been specifically engineered for a range of biomedical applications, including but not limited to, artificial pancreas, hemodialysis, andsynthetic vitreous humor [80,53], Moreover, PVA is employed in the development of implantable medical materials owing to its favorable attributes, such as biocompatibility

[0081] , low protein adsorption leading to reduced cell adhesion, high water solubility, biodegradability, low environmental impact, and chemical resistance in comparison to alternative polymers

[0048] , In addition, previous studies reported that compared with other polymers, such as polyurethane, PVA induces less accumulation of inflammatory cells [48,82,83],

[0011] Despite its excellent physical and tunable mechanical properties, PVA must be crosslinked by either physical or chemical methods [84,85] for many applications. Crosslinking PVA improves certain inherent drawbacks (e.g., superhydrophilic nature and high water solubility) of the polymer. Such drawbacks contribute to accelerated degradation and substantial absorption.

[0012] There is a continuing need in the art for additional and alternative approaches to providing for bio-compatible materials that avoid blood clot formation, and biofouling.SUMMARY

[0013] A method for bulk modification that enables the creation of highly flexible, lubricant- infused silane-crosslinked polyvinyl alcohol (PVA) films. In embodiments, the films are fluorine-free. This approach incorporates lubricant-infused properties throughout the entire volume of the film. The fabrication process involves adding an organosilane crosslinking agent, such as an alkyl silane crosslinking agent, and more specifically propyl trichlorosilane (nPTCS), to the PVA polymer solution, followed by forming a film, e.g., casting a film, and infusion of the film with a compatible lubricant, such as silicone oil, to produce a lubricant-infused PVA film. In embodiments, optimization of silane crosslinking agent concentration in the PVA films is conducted through morphological, chemical, thermal, and mechanical characterization of the films.

[0014] In embodiments, the amount of silane crosslinking agent added afffects the extent of crosslinking in the film and the properties, particularly the mechanical properties, of the film. The method of this disclosure successfully creates PVA films with the appropriate chemical affinity to effectively lock in the lubricant, particularly a silicone oil lubricant, resulting in stable LIS that exhibit significantly enhanced antibacterial and antithrombotic properties compared to control PVA film samples.

[0015] In embodiments, the lubricant infuses into the crosslinked PVA film. In embodiments, the lubricant infuses into the crosslinked PVA film and a layer of lubricant remains on the surface of the crosslinked PVA film. Moreover, crosslinking PVA chains and the formation of strong covalent bonds between them results in films with significantly enhanced degradation and mechanical properties, especially in terms of elasticity and flexibility.ln embodiments, the disclosure provides a class of silane-crosslinked PVA films that are infused with lubricant to provide LIS with a durable lubricant-infused structure.

[0016] In embodiments, the PVAthat is to be corsslinked ranges in Mw (weight average molecular weight) from 5,000 to 200,000 D. In embodiments, the PVAthat is to be crosslinked ranges in Mw from 20,000 to 200,000 D. In embodiments, the PVAthat is to be crosslinked ranges in Mw (weight average molecular weight) from 50,000 to 150,000 D. In embodiments, the PVAthat is to be crosslinked ranges in Mw from 75,000 to 100,000 D. In embodiments, the PVAthat is to be crosslinked ranges in Mw from 89,000 to 98,000 D. In embodiments, the PVAthat is to be crosslinked has a degree of hydrolysis of 70% or more. In embodiments, PVAthat is to be crosslinked has a degree of hydrolysis of 80% or more. In embodiments, PVAthat is to be crosslinked has a degree of hydrolysis of 90% or more. In embodiments, PVAthat is to be crosslinked has a degree of hydrolysis of 95% or more. In embodiments, PVAthat is to be crosslinked has a degree of hydrolysis of 99% or more.

[0017] In embodiments, the lubricant is silicone oil. In embodiments, the silcone oil has viscosity ranging from 10-1000 cSt. In embodiments, the silicone oil is medical-grade silicone oil. In embodiments, the silicone oil has viscosity of 250-450 cSt. In embodiments, the silicone oil has viscosity of 325 to 375 cSt. In embodiments, the silicone oil has viscoity of 350 cSt. In embodiments, the fabrication process involves the incorporation of a silane-based crosslinking agent, particularly an organosilane, more particularly an alkyl trichlorosilane, and more particularly propyl trichlorosilane (nPTCS), into a PVA polymer solution and generation of a cross-linked PVAfilm. Generation of the film is followed by infusion of silicone oil on the surface of the film to create a lubricant-infused PVA film. The silicone oil infuses into the bulk of the crosslinked film. The crosslinking of PVA yields significant enhancements in both the bulk and surface properties of the film.

[0018] In embodiments, the silane-based crosslinking agent is an organosilane of formula I: Ri R2R3-Si-X, where: each Ri is independently, an optionally substituted alkyl group, an optionally substituted cycloalkyl group, an optionalluy substituted alkenyl group, an optionally substituted aryl group, hydtrogen or a siloxane group of formula:-O-Si-(R4)3;R2is Ri or X; R3is Ri or X; each R4independently is an optionalluy substituted alkyl group, a optionally substituted cycloalkyl group, an optionally substituted alkenyl group, an optionally substituted alkoxy group or an optionally substituted aryl group; and each X is independently Cl, alkoxy, or acyloxy (-O-CO-R), where R is an optionally substituted alkyl group having 1 to 3 carbon atoms, an optionally substituted cycloalkyl having 6-12 carbon atoms or an optionally substituted phenyl group.

[0019] In embodiments, optional substitution for alkyl groups is one or more optionally substituted phenyl, one or more optionally substituted benzyl groups, one or more optionally substituted cycloalkyl groups having 3-12 carbon atoms or one or more optionally substituted alkenyl groups having 2-4 carbon atoms. In embodiments, optional substitution for cycloalkyl groups is one or more optionally substituted alkyl groups having 1-3 carbon atoms, one or more optionally substituted alkenyl groups having 2-4 carbon atoms, one or more optionally substituted alkoxy groups havign 1-3 carbon atoms, one or more optionally substituted phenyl groups, or one or more optionally substituted benzyl groups.

[0020] In embodiments, R is an unsubstituted alkyl group having 1 to 3 carbon atoms, an unsubstituted phenyl group or an unsubstituted benzyl group. In embodiments, R is a phenyl or benzyl group substituted with one or more alkyls having 1-3 carbon atoms, one or more alkenyl having 2-4 carbon atoms, or one or more alkoxy having 1-3 carbon atoms. In embodiments, R is an alkyl or cycloalkyl substituted with one or more optionally substituted phenyl or benzyl groups. In embodiments, R is an alkyl substituted with one or more optionaly substituted alkoxy groups having 1-3 carbon atoms. In embodiments, R is a cycloalkyl substituted with one or more optionally substituted alky groups having 1-3 carbon atoms or oen or more optionally substituted alkoxy groups having 1-3 carbon atoms.

[0021] In embodiments, R2and R3are both Cl. In embodiments, Ri is an unsubstituted alkyl group having 1-6 carbon atoms or 2-4 carbons.

[0022] In embodiments, the silane crosslinking agent is n-propyltrichlorosilane, methyltrichlorosilane, ethyltrichlorosilane, n-butyltrichlorsilane, phenyltrichlorosilane, benzyltrichlorsilane, vinyltrichlorosilane or cyclohexyltrichlorosilane.

[0023] In embodiments, the silane crosslinking agent is trimethyoxysilane, triethoxysilane, or triacetyloxysilane.

[0024] In embodiments, the silane crosslinking agent is phenyltrialkoxysilane, vinyltrialkoxysilane, or cyclohexyltrialkoxy silane. In embodiments, the silane crosslinking agent is phenyltrimethoxysilane, vinyltrimethoxysilane, or cyclohexyltrimethyoxysilane. In embodiments, the silane crosslinking agent is phenyltriethoxysilane, vinyltriethoxysilane, or cyclohexyltriethyoxysilane.

[0025] In embodiments, the silane crosslinking agent is methyltriacetyloxysilane, ethyltriacetyloxysilane, vinyltriacetyloxysilane, n-propyltriacetyloxysilane or phenyltriacetyloxysilane.

[0026] In embodiments, R is a methyl or an ethyl group. In embodiments, R is an unsubstituted phenyl or benzyl group. In embodiments, X is an alkoxy having 1-3 carbon atoms.

[0027] In embodiments, Ri that is an alkyl group has 1-3 carbon atoms. In embodiments, Ri that is an alkenyl group has 2-4 carbon atoms. In embodiments, Ri that is a cycloalkyl group has 3-6 carbon atoms. In embodiments, Ri that is an aryl group is an optionally substituted pheny, biphenyl, styryl, benzyl or naphthyl group. In embodiments, R4that is an alkyl group has 1-3 carbon atoims. In embodiments, R4that is an alkenyl group has 2-4 carbon atoms. In embodiments, R4that is acycloalkyl group has 3-6 carbon atoms. In embodiments, R4that is an aryl group is an optionally substituted pheny, biphenyl, benzyl or naphthyl group.

[0028] In embodiments, X is Cl, methoxy, ethoxy or acetyloxy. In embodiments, each Ri is independently methyl, ethyl, n-propyl, iso-propyl, n-butyl, isobutyl, vinyl, cyclohexyl, phenyl or benzyl. In embodiments, R2is X. In embodiments, R2and R3are both X. In embodiments, each of R2and R3is Cl. In embodiments, each of R2annd R3is methoxy. In embodiments, each of R2annd R3is ethoxy. In embodiments, each of R2and R3is acetyloxy (-O-CO-CH3).

[0029] In embodiments, X is a halogen other than F. In embodiments, X is Cl. In embodiments, both of R2and R3are X. In embodiments, both of R2and R3are Cl. In embodiments, X is Cl and both of R2and R3are Cl.

[0030] In embodiments, at least one of R-i is -O-Si-(R4)3In embodiments, one of Ri is -O-Si- (R4)3In embodiments, two of Ri are -O-Si-(R4)3In embodiments, three of Ri are -O-Si-(R4)3In embodiments, each R4is an alkyl group having 1-3 carbon atoms. In embodiments, each R4is the same group. In embodiments, each R4is a pheny or a benzyl group. In embodiments, each R4is a vinyl group. In embodiments, each R4is a methoxy or ethoxy group.

[0031] In embodiments, each of RI-R3is an alkyl group having 1-3 carbon atoms. In embodiments, Ri is an alkyl group having 1-3 carbon atoms and R2and R3are each X. In embodiments, Ri and R2are alkyl groups having 1-3 carbon atoms and R3is X.

[0032] In embodiments, the silane crosslinking agent is n-propyltrichlorosilane, methyltrichlorosilane, ethyltrichlorosilane, n-butyltrichlorsilane, phenyltrichlorosilane, benzyltrichlorsilane, vinyltrichlorosilane or cyclohexyltrichlorosilane

[0033] In embodiments, the silane crosslinking agent is n-propyltrichlorosilane, methyltrichlorosilane, ethyltrichlorosilane, n-butyltrichlorsilane, phenyltrichlorosilane, benzyltrichlorsilane, vinyltrichlorosilane or cyclohexyltrichlorosilane.

[0034] In embodiments, the silane crosslinking agent is trimethyoxysilane, triethoxysilane, or triacetyloxysilane.

[0035] In embodiments, the silane crosslinking agent is phenyltrialkoxysilane, vinyltrialkoxysilane, or cyclohexyltrialkoxysilane. In embodiments, the silane crosslinking agent is phenyltrimethoxysilane, vinyltrimethoxysilane, or cyclohexyltrimethyoxysilane. In embodiments, the silane crosslinking agent is phenyltriethoxysilane, vinyltriethoxysilane, or cyclohexyltriethyoxysilane.

[0036] In embodiments, the silane crosslinking agent is methyltriacetyloxysilane, ethyltriacetyloxysilane, vinyltriacetyloxysilane, n-propyltriacetyloxysilane or phenyltriacetyloxysilane.

[0037] In an embodiment, crosslinking is achieved through a streamlined one-pot fabrication method. Bulk modification happens via the formation of strong covalent bonds between polymer chains, and the silane crossing linking agent to enhance bulk properties such as stability, degradation, and significant enhancement of mechanical properties, particularly elasticity and flexibility. Also, crosslinking simultaneously reduces the number of available polymer hydroxyl groups,leading to increased hydrophobicity. Surface modification is believed to be the result of crosslinked polymer chains present in the film, membrane or coating and in-situ self-polymerization of silane crosslinker molecules. It is believed that the process leads to an enhanced affinity between the PVA film, membrane or coating and the infused lubricant, e.g., silicone oil. In embodiments, the process disclosed obviates the need for additional film surface modification with silane-based agents.

[0038] The invention provides a method for making a silane-crosslinked poly(vinyl alcohol) (PVA) film comprising:(a) generating a film-forming solution by adding a seleted amount of a silane crosslinking agent and a selected amount of PVA to a selected solvent; and(b) forming a film of crosslinked PVA from the film-forming solution.

[0039] In embodiments, the selected solvent is an aqueous solvent. In embodiments, the selected solvent is water. In embodiments, the aqueous solvent is a miscible mixture of an alkyl alcohol (preferably an alkyl alcohol having 1-3 carbon atoms) in which PVA is soluble. In embodiments, the aqeous solvent comprises ethanol or isopropanol. In embodiments, the aqueous solvent contains up to 10% by volume ethnaol or isopropanol. In embodiments, the film is formed by casting the film-forming solution onto one or more surfaces, or into a mold and removing the solvent. In embodiments, the film is formed by spray-coating of the film-forming solution onto one or more surfaces and removing solvent.

[0040] More specifically, the invention provides a method for making a silane-crosslinked poly(vinyl alcohol) (PVA) film comprising:(a) adding a selected amount of a silane crosslinking agent to an aqueous solution of PVA to generate an aqueous film-forming solution; and(b) forming a film of silane-crosslinked PVA from the film-forming solution.

[0041] The crosslinked PVA film is generally formed by any known method. In embodiments, the crosslinked PVA film is formed by casting the film-forming solution containing the silane- crosslinking agent and PVA onto a substrate and removing solvent from the solution in contact with the surface. In embodiments, the crosslinked PVA film is formed by spray-coating of a surface (e.g., of a substrate) of the film-forming solution containing the silane-crosslinking agent and PVA onto a substrate and removing solvent from the coated solution to form the film on the surface. The substrate may be one or more surfaces or a mold. In embodiments, the selected solvent is an aqueous solvent. In embodiments, the selected solvent is a miscible mixture of an alkyl alcohol and water. In embodiments, the selected solvent is a miscible mixture of ethanol and water in which the selected amount of PVA is soluble. In embodiments, the selected solvent is a miscible mixture of isopropanol or ethanol and water in which the selected amount of PVA is soluble. In embodiments, the seleted solvent is water. More specifically, the selected solvent is distilled water.

[0042] In embodiments, the silane-crosslinked poly(vinyl alcohol) (PVA) film exhibits roughness as measured by SEM.

[0043] In embodiments, the silane-crosslinked poly(vinyl alcohol) (PVA) film comprises silicon nano- or microparticles. In embodiments, the silcon particles can range in average size from 10 nm to 1 micron. In embodiments, the silicon nano- or microparticles are formed by self-polymerization of the organosilane crosslinking agent. In embodiments, silicon nano- or microparticles in addition to those formed by self-polymerization can be added to the film-forming solution prior to forming the crosslinked PVA film. In embodiments, no silicon nano- or microparticles are added to the film-forming solution or to the crosslinked PVA film. In embodiments, any silicon nano- or microparticles in the cosslinked PVA film are those that may be formed during crosslinking of the PVA.

[0044] In embodiments, the amount of silane crosslinking agent added to the solution of PVA ranges from 1% to 40% (volume of liquid crosslinking agent to volume of the polmer solution, v / v). In embodiments, the amount of crosslinking agent added ranges from 5% to 35% v / v, from 9% to 31% v / v, from 10% to 30% v / v, from 5% to 20% v / v, from 5% to 15% v / v, from 5 to 10% v / v or from 10% to 20% v / v. In additional embodiments, the amount of silane crosslinking agent added is from 7% to 13% v / v or 8% to 12% v / v.

[0045] In embodiments, the selected amount of PVA dissolved in the solution ranges from 5% to 30% weight / volume. In embodiments, the selected amount of PVA dissolved in the solution ranges from 10%-20%, 10%-15%, or 10%-30%. In embodiments, the PVA is added to distilled water. In embodiments, the PVA is added to a miscible mixture of ethnaol and water. In embodiments, the PVA is added to a miscible mixture of water and 10% or less by volume ethanol.

[0046] In embodiments, the selected solvent is an aqueous solvent, water or an aqueous buffer. In embodiments, the pH of the aqueous solvent ranges from 6.0 to 8.0. In embodiments, distilled water is used. In embodiments, the water employed is deionized. In embodiments, the water employed is ultra pure. In embodiments, the purity of water employed or the use of a buffer can be adjusted depending upon the intended application of the film. In embodiments, the aqueous solvent is a miscible mixture comprising an alkyl alchol and water, particularly where the alkyl alcohol has 1-3 carbon atoms. In embodiments, the alkyl alcohol is ethanol or isopropanol. In embodiments, the aqueous solvent is a miscible mixture of water and alkyl alcohol in which the selected amount of PVA and silane crosslinking agent are soluble. In embodiments, the

[0047] In embodiments, the aqueous solution of PVA is formed by addition of a selected amount of solid PVA to aqueous solution with stirring to dissolve the PVA. In embodiments, the aquoeus solution of PVA is formed by addition of solid PVA to water at a temperature of 70-90°C with stirring to dissolve PVA. In embodiments, the aqeous solvent is water. In embodiments, the aqueous solution is a miscible mixture of ethanol and water in which the selected amount of PVA is soluble. In embodiments, the aqueous solution is a miscible mixture of water and less than 10% (v / v) of ethanol in which the selected amount of PVA is soluble.

[0048] In embodiments, the aqueous solution containing silane-crosslinked PVA is heated to a temperature ranging from 50° to 80°C for 1-12 hours prior to film formation. In embodiments, theaqueous solution is heated to 70°C for 2-4 hours or more specifically for 3 hours prior to film formation. In embodiments, the aqueous solution containing silane-crosslinked PVA is cooled to room temperature prior to film formation. In embodiments, solvent is removed from the film as it forms at room temperature and ambient pressure. In embodiments, the solution after casting or spray-coating is heated to a temperature of 30° to 80°C to remove solvent. In embodiments, the solution after casting or spray-coating is subjected to subambient pressure to facilitate solvent removal. In embodiments, the film generated ranges in thickness from 200-400 micron. In embodiments, the substrate upon which the film is formed is selected from plastic, glass, quartz, or metal. In embodiments, the filmed formed is self-supporting.

[0049] In embodiments, the silane-crosslinked poly(vinyl alcohol) (PVA) film as described herein is infused with an appropriate lubricant. In embodiments, the lubricant is silicone oil. In embodiments, infusion comprises contacting the silane-crosslinked poly(vinyl alcohol) (PVA) film with an excess of lubricant and removing excess lubricant that is not absorbed into the film.

[0050] In embodiments, the surface of the silane-crosslinked poly(vinyl alcohol) (PVA) film is infused with a selected amount of silicone oil, tyipcally in excess, for a time sufficient for infusion into the bulk material of the film after which excess lubricant is removed from the film. In embodiments, the excess lubricant is removed from the lubricated film by holding the film at a tilt angle of about 45° for a time sufficient to remove excess lubricant from the film. In embodiments, the silane-crosslinked poly(vinyl alcohol) (PVA) film is washed with water and dried prior to infusion of the silicone oil. In embodiments, the silicone oil in excess is infused into the film for a time ranging from 12-24 hours and then the lubricated film is held at the titlt angle for a time ranging from 12-24 hours to remove excess lubricant from the film. In embodiments, all steps for film infusion at conducted at about room temperature.

[0051] In embodiments, the invention provides a silane-crosslinked poly(vinyl alcohol) (PVA) film crosslinked with a silane-crosslinking agent of formula I (above). The silane crosslinking agent can be any one or more such agent as described in embodiments herein. In embodiments, the silane- crosslinked poly(vinyl alcohol) (PVA) film exhibits surface roughness as measnured by SEM. In embodiments, the silane-crosslinked poly(vinyl alcohol) (PVA) film comprises nano- or microparticles formed from self-polymerization of the organosilane crosslinking agent. In embodiments the silane- crosslinked poly(vinyl alcohol) (PVA) film does not exhibit surface roughness as measured by SEM.

[0052] In embodiments, the invention provides a lubricated silane-crosslinked poly(vinyl alcohol) (PVA) film. In embodiments, the silane crosslinked PVA film is lubricated with silicone oil.

[0053] In embodiments, the silane-crosslinked PVA film and the corresponding lubricated silane-crosslinked PVA film exhibts improved mechanical properites compared to uncrosslinked PVA.

[0054] In embodiments, the invention provides an article having at least one surface, a portion of which surface contacts a biological fluid, wherein the portion of the at least one surface is coated or covered with a silane-crosslinked PVA film infused with silicone oil. In embodiments, the article is adrug delivery device. In embodiments, the article is a medical device (including among others a stent, catheter, a heart valve, or a surgical instrument). In embodiments, the biological fluid is a human or other animal body fluid. In embodiments, the biological fluid is blood. In embodiments, the biological fluid is plasma. In embodiments, the fluid is a fluid that contains one or more microorganisms (e.g., one or more bacterium).

[0055] In embodiments, the invention provides a method of preventing biofouling of an article surface or a device surface that contacts a fluid that contains one or more microorganisms or any biological fluid, the method comprising providing a lubricant-infused silane-crosslinked PVAfilm on the surface of the article or device that contacts the fluid. In embodiments, the film is formed by casting or spray-coating a film-forming solution on a selected portion of a selected surface or substrate to form a silane crosslinked PVAfilm and lubricating the silane crosslinked PVA film on the selected portion of a selected surface or substrate with lubricant, preferably silicone oil. In embodiments, the silicone oil is medical grade silicone oil.

[0056] Additional aspects and embodiments of the disclosure will be apparent to one of ordinary skill in the art on review of the following detailed description, figures and non-limiting examples.Brief Description of the Drawings

[0057] Figure 1 A includes photos (first row) and scanning electron microscopy (SEM) images (middle and bottom rows) of control PVA and crosslinked sample cast films formed before lubrication. These images are used to study the microstructure and morphology differences in the films as the amount of silane crosslinking agent (e.g., n-PTCS) in the samples is increased. Samples labeled as PVA, PS1 , PS5, PS10, PS20, and PS30, corresponding to 0%, 1%, 5%, 10%, 20%, and 30% (volume liquid crosslinking agent to volume of polymer solution) n-PTCS in samples, respectively. The photos of the films in the top row show the area images by SEM. The middle row of SEM images is at 50pm resolution and the bottom row of images is at 5 pm resolution.

[0058] Figure 1 B includes graphs illustrating energy-dispersive X-ray spectroscopy (EDS) elemental analysis of PVA samples of Fig. 1 A before (PVA) and after crosslinking (PS1-PS30) presenting the elemental composition within the films.

[0059] Figure 2A is a schematic illustration of an exemplary crosslinking reaction mechanism between the hydroxyl groups of the PVA polymer chain and the silane crosslinking agent, exemplified for an alkyltrichlorosilane crosslinking agent via a condensation reaction. Initially, the alkyltrichlorosilane (e.g., n-PTCS) molecules are believed to undergo at least partial hydrolysis in the polymer solution (reaction 1) , reacting with water molecules, substituting one or more chlorines with hydroxyl groups and releasing HCI. PVA chains are then believed to interact with the hydrolyzed n- PTCS molecules through a condensation reaction (reaction 2).

[0060] Figure 2B is a graph illustrating ATR-FTIR spectra of the samples of Fig. 1A. By adding n-PTCS to the PVA films, the intensity of the band related to the -OH stretching vibration decreased (peak a), and additional peaks corresponding to the Si-O-C and Si-O-Si (c and d) bands were observed when comparing PS samples with pure PVA indicating crosslinking of the hydroxyl groups on the PVA backbone. Samples labeled as PVA, PS1 , PS5, PS10, PS20, and PS30, correspond to 0%, 1%, 5%, 10%, 20%, and 30% (v / v) n-PTCS in samples, respectively.

[0061] Figure 2C lubricant acquisition result graph (n=3, *** P<0.05, ****P<0.0001) indicating the weight (mg) of silicone oil retained by various sample films (PS1-PS30).

[0062] Figure 2D illustrates XRD patterns of the samples as labelled.

[0063] Figure 2E illustrates TGA curves of the samples s labelled.

[0064] Figure 2F illustrates the DSC curves of the samples and shows the trends in melting temperature (Tm) and glass transition temperature (Tg) with increasing amount of crosslinker. Solid line (PVA); heavy long dashed ( - ) line (PS1); dotted / dashed ( - ) line (PS5); medium dashed line ( - ) (PS10); dotted line (• • •) (PS20); and short dashed line ( — ) (PS30).

[0065] Figure 3A illustrates images of water droplet absorption on a film surface taken at different time points as indicated. Samples labeled as PVA, PS1 , PS5, PS10, PS20, and PS30, correspond to 0%, 1%, 5%, 10%, 20%, and 30% (v / v) n-PTCS in samples, respectively.

[0066] Figure 3B is a graph of static contact angle of a water droplet (5 microL) on PVA control film and PS lubricated and non-lubricated film samples (n=4) labeled as in Fig. 1A.

[0067] Figure 3C illustrates sliding angle measurements of 5 microL water (open circles) and blood (closed circles) droplets on the PVA control and lubricated PS sample films (labeled as in Fig.1 A). Measurements on the left were at week 1 and measurements on the right were at week 3. In PVA samples in which the droplet did not move, a sliding angle of 90° was measured (n=3).

[0068] Figure 3D is a graph of swelling (%) on non-lubricated control film (PVA) and lubricated (open circles) and non-lubricated (closed circles) PS film samples. There is a significant decrease in the swelling ratio of PS samples compared to PVA, with further reduction observed in PS samples after lubrication.

[0069] Figure 3E illustrates images of the control PVA film and and lubricated PS film samples taken of the film degradation process at 0 and 8 weeks to monitor the deformation and stability of the samples in water.

[0070] Figure 3F is graph showing degradation curves of the control PVA and lubricated PS film samples over 8 weeks of soaking in water (n=3) measuring weight Ioss9%) as a function of time. (n=3, *P<0.05, ****P<0.0001). PVA (closed circles); PS1-L (closed triangles); PS5-L (closed squares); PS10-L (closed diamonds); PS20-L (open circles); PS30-L (closed inverted triangles).

[0071] Figure 4A illustrates images of the samples (labelled as in Fig. 1A) at the start point and Ultimate Tensile Strength (UTS) point of the uniaxial tensile test. The samples were elongated at a rate of 5 mm / min until the rupture point.

[0072] Figure 4B is a graph providing Stress-Strain curves of the samples obtained from the uniaxial tensile strength test illustrated in Fig. 4A. PVA (solid line); PS1-L (dark short dashed line, — -); PS5-L (dotted line, • • •); PS10-L (dashed / dotted line, - ); PS20-L (light short dashed line, -); PS30-L (long heavy dashed line, - ).

[0073] Figures 4C-4E illustrates graphs of Young’s modulus (Fig. 4C), Elongation at the UTS (Fig. 4D), and Tensile strength (FIG, 4E) of the samples (labelled as in Fig. 1A) obtained from the stress-strain curve of Fig. 4B.

[0074] Figure 4F is a graph showing the stress-induced curve of the samples (labelled asin Fig. 1A) obtained from the bending test, where a dynamic uniaxial tensile load was applied over 1000 cycles using a sinusoidal function at a frequency of 0.5 Hz. PVA (closed circles); PS1-L (open circles); PS5-L (closed squares); PS10-L (closed diamonds); PS20-L (inverted closed triangles); PS30-L (closed triangles).

[0075] Figure 4G illustrates images of the samples (labelled as in Fig. 1A) during the twisting test, before the rupture and at the rupture point (inset images).

[0076] Figure 4H is a graph of the results of the twisting test with samples labelled as in Fig. 1A (n=3, *P<0.05, ***P<0.0005, ****P<0.0001).

[0077] Figure 5A is a graph of stress curves of the film samples (control PVA and lubricated crosslinked films, as indicated) obtained from the tensile fatigue test while employing a pre-tension of 0.5 N for 30% displacement through 1000 cycles. PVA (closed circles); PS1-L (open circles), PS5-L (closed squares); PS10-L (closed diamonds); PS20-I (closed triangles); PS30-L (closed inverted triangles).

[0078] Figure 5B is a graph of stress retention results from the suture retention test indicating the high elasticity and tensile strength of the lubricant-infused crosslinked (PS-L) samples. Samples labeled as PVA for pure PVA and PS1-L, PS5-L, PS10-L PS20-L, and PS30-L, corresponding to the lubricant-infused samples including 0%, 1%, 5%, 10%, 20%, and 30% n-PTCS, respectively. (n=3, *P<0.05, ***P<0.0005, ****P<0.0001).

[0079] Figure 6Ais a graph showing thrombus (clot) mass (mg) adhered to the surface of the PVA control and PS10-L samples after performing the whole blood clotting assay (n=5).

[0080] Figure 6Bis a graph of plasma clotting times (sec) of control PVA and PS10-L samples (n=18).

[0081] Figure 6C is a graph of the relative absorbance of the solution obtained after rinsing the samples in blood stamping test, indicating fewer adhered blood cells on PS10-L samples compared to PVA samples.

[0082] Figure 6D is a graph of the results of the blood clotting start time test, indicating a significant delay in PS10-L samples in contract with the control PVA samples. Samples labeled as PVA for pure PVA, and PS10-L corresponding to lubricant-infused samples including 10% n-PTCS. (n=6, *P<0.05, ***P<0.0005, **** P<0.0001).

[0083] Figure 7A is a graph of plate coverage percentage of bacterial colonies from the migration test (*P<0.05, ***P<0.0005, ****P<0.0001).

[0084] Figure 7B is a graph of the number of detached bacteria (CFU / mL) from each sample, quantified using the serial dilution method. (n=5) (*P<0.05, ***P<0.0005, ****P<0.0001).

[0085] Figure 7C is a graph illustrating the results of the bacterila stamping test quantified by the number of the bacteria transferred and adhered to the stamped samples (CFU / mL) (n=5). (*P<0.05, ***P<0.0005, ****P<0.0001).

[0086] Figure 8 illustrates the complete Raman spectra for the control and crosslinked samples (PVA, PS1 , PS5, PS10, PS20 and PS30). In the spectrum of polyvinyl alcohol (PVA), notable scattering peaks appear around 2912 cm-1 attributed to the stretching vibrations of CH2, and additional peaks at 1440 cm-1 attributed to the stretching vibrations of CH and OH in in the PVA molecules. On addition of n-PTCS as a crosslinker, two main peaks appeared at 490 cm-1 and 1000 cm-1 , which are attributed to the Si-O-Si bonds formed between the n-PTCS molecules through condensation reactions in the aqueous polymer solution. Upon crosslinking, in addition to the Si-O-Si peak, another peak at 590 cm-1 is observed that can be assigned to the stretching of Si-CI bonds in the crosslinker agent. The figure includes an expansion of the wavelength region from 300 to 700 cm- 1. The intensity of the peaks in this region at 2995 cm-1 and 3300 cm-1 increased with increasing n- PTCS concentration. These peaks are attributed to the -CH3and -CH2bonds that are abundant in the crosslinker as the n-propyl group.Detailed Description

[0087] The invention provides a novel method for the bulk modification of polyvinyl alcohol (PVA) films to create highly flexible lubricant-infused surfaces with superior antifouling properties. By adding a silane crosslinking agent, as exemplified by propyl trichlorosilane (nPTCS), into the PVA matrix and infusing the resulting crosslinked films with silicone oil, a robust and stable lubricant- infused surface throughout the bulk of the material can be prepared. This approach overcomes the limitations of traditional lubricant-infused surface technologies that are often constrained to thin surface coatings, which can be ineffective under mechanical stress. Crosslinked PVA films and crosslinked lubricated PVA films demonstrate significant improvements in both mechanical properties and biological performance. Compared with control PVA samples, the silane-crosslinked PVA films show significantly decreased degradation rate and increased thermal stability along with high tensile strength and elongation of more than four-fold. With further modification of the crosslinked surface with silicone oil as a lubricant layer, these surfaces become highly repellent and prevent non-specific adhesion of blood and bacteria and increased plasma and whole blood clotting time. These results demonstrate that the lubricant layer is effectively integrated throughout the bulk PVA material and provides long-lasting and comprehensive antifouling protection. The results highlight the benefits of this bulk modification technique in advancing the development of biointerfaces for medical applications.

[0088] By addressing the issues associated with surface-only coatings, this method offers a more reliable solution for preventing biofouling in clinical settings. The enhanced stability and functionality of these crosslinked lubricant-infused PVA films indicate that they can serve as a valuable alternative to traditional antifouling strategies, with broad applications in medical devices and implants.

[0089] The invention generally relates to so-called slippery surfaces formed by combining a lubricating fluid with a polymer where the polymer absorbs the lubricating liquid and a lubricating layer is formed on the surface of the polymer. Such surfaces can also be called Lubricant-infused surfaces (LIS). Such surfaces may also be designated slippery self-lubricating polymer surfaces, as for example in U.S. patent 11 ,186,731 (which is incorporated by reference herein for all purposes).

[0090] In embodiments, a polymer film is contacted with a lubricant that is absorbed into the polymer, which may swell as a result of the absorption and in addition a layer of lubricant is formed on the surface of the swelled polymer. The LIS can be formed and used as a coating or layer upon a substrate surface or the LIS can be formed as a self-supporting film or membrane. The lubricant employed is believed to have an affinity for the polymer such that the lubricant is absorbed into the film. In embodiments, the layer of lubricant formed on the surface of the LIS repels certain liquids and solids that it comes into contact with, such that they do not adhere to the surface. In embodiments, the liquids and solids that are repelled are biological fluids, microorganisms or other components present in biological fluids (e.g., proteins). LIS that repel such biological fluids are useful in a varietyof applications for protecting surfaces that come into contact with biological fluids from biofouling and other damage. In general, for use in such applications, the biological fluid is not soluble in the lubricant of the LIS.

[0091] In embodiments, the LIS is self-healing in that the layer of lubricant formed on the surface of the LIS can be replenished from the underlying polymer which has absorbed the lubricant, if the surface layer of lubricant is damaged.

[0092] The term film is used generically herein to refer to any layer, coating or membrane that is used to form the LIS. The film may be supported on a substrate (on the surface of a substrate) or may be in the form of a self-supporting film or membrane. In specific embodiments, the film employed herein to form the LIS is a crosslinked poly(vinyl alcohol) film. More specifically, the film is a silane crosslinked PVA film. In embodiments, the film is formed on a substrate and remains on the substrate, which for example can be a surface (or portion of a surface) of an article or device that is intended to contact biological fluids. In embodiments, the film is formed on a substrate and is removed from the substrate to be used as a free-standing film or membrane. Infusion of lubricant can be done while the film is supported on a substrate or before or after the free-standing film is removed from the substate.

[0093] In general, any known method for forming a film from a film-forming solution containing polymer can be used to form the crosslinked film herein. In embodiments, films are formed by dispersing the film-forming solution on a surface and removing solvent to form the film. In embodiments, herein the film-forming solution contains a selected amount of one or more silane- crosslinking agents and a selected amount of PVA (of selected Mw and degree of hydrolysis). In embodiments, the film-forming solution is dispersed by casting the solution on a surface or by spraycoating the solution on a surface. In embodiments, one or more steps of casting of the film-forming solution with solvent removal can be employed to form the crosslinked film. In embodiments, one or more steps of spray-coating of the film-forming solution on the surface with solvent removal can be employed to form the crosslinked film. In embodiments, the film-forming solution comprises one or more silane crosslinking agents and PVA. In embodiments, the film-forming solution consists of one or more silane crosslinking agents and PVA. In embodiments, the film-forming solution consists essentially of one or more silane crosslinking agents and PVA and does not contain any component that detrimentally affects crosslinking and ultimate formation of LIS. Films of this invention optionally contains one or more art-recognized film additives, such as plasticizer, stabilizer (e.g., antioxidant, or UV stabilizer) or filler. In embodiments, the film forming solutions do not contain added fillers. In embodiments, the film-forming solutions contain added nano- or microparticles, particularly silicon based particles. In embodiments, film-forming solutions do not contain added nano- or microparticles. In embodiments, film-forming solutions do not contain added silica (SiO2particles), particularly SiO2nanoparticles.

[0094] A silane crosslinked PVA is a film formed from PVA that is at least in part crosslinked with one or more organosilane crosslinking agents. In embodiments, the film is crosslinked with one or more organosilane crosslinking agents of formula I. In embodiments, the film is crosslinked with a mixture of two organosilane crosslinking agents of formula I. The extent of PVA crosslinking can be adjusted as described in examples herein to select physical properties of the resultant crosslinked film by varying the choice of organosilane crosslinking agent(s) used for crosslinking and by varying the amount of organosilane crosslinking agent(s) added to PVA solution to accomplish the crosslinking. In addition, the Mw of the PVA that is crosslinked can be varied to adjust physical properties of the crosslinked film.

[0095] The LIS herein can in general be provided to (added to, coated on, or applied to) any surface that comes in contact (or may come in contact) with a biological fluid and that needs protection from fouling by that biological fluid. In particular, the LIS herein can be applied to or formed on a surface (or a portion of a surface) of any article or device that is or may be exposed to a biological fluid. Articles include, for example, fluid conduits (e.g., pipes or tubes), seals (flanges, o- rings and the like), optical articles (lens and the like), medical devices inserted into and / or retained in the body (human or other animal), for example drug delivery devices and diagnostic devices. The surface to which the LIS is applied or on which it is formed can in general be any material, typically a material that can be safely employed in applications in contact with biological fluids, including various ceramics, plastics, glass, quartz or various metals.

[0096] In embodiments, the surface(s) intended to carry the LIS of the invention include one or more surfaces of a medical device (e.g., a catheter, a stent, a heart valve), a surgical tool (e.g., scalpel, clam, etc.), fluidic conduits and surfaces of machines that contact blood or other biofluids (e.g., dialysis machines, pumps, fluid dispensers), medical implants, biosensors including lab-on-a chip-devices.

[0097] In embodiments, the surface(s) provided with the LIS of the invention include those of any equipment, including, for example, conduits, pipes and fluid containers, for fluid transport or chemical or biochemical processing. In embodiments, surfaces to be provided with the LIS of the invention are fluid handling systems and other equipment used in food and beverage processing. In embodiments, the LIS is provided on one or more surfaces of a fermentation vessel.

[0098] In embodiments, surfaces to be provided with the LIS of the invention are those of marine vessels or objects or machines that contact the marine environment to reduce biofouling.

[0099] In embodiments, LIS surfaces of the invention can be employed in consumer products that come in frequent contact with the human or animal body, such as eyeglasses, hearing aids, and consumer electronics touchscreens, touchpads, mice and the like. In embodiments, LIS surfaces of the invention can be employed in protective coatings for wearable devices, protective clothing (including masks and other PPE). In embodiments, LIS surfaces of the invention can be employed in medical or food packaging applications, for example, in contact with blood or other biological fluids.

[0100] In general, LIS of this invention are useful in medical and pharmaceutical applications, in industrial applications, in marine coatings, in diagnostic devices to preserve surfaces from biofouling, protective coatings, packaging applications and in consumer product production, e.g., production of consumer electronics.

[0101] The LIS of this invention are prepared by lubricating a silicon-crosslinked PVA film with an appropriate lubricant. In embodiments, the lubricant is silicone oil. Silicone oil is a liquid (typically assessed at room temperature) that is a siloxane polymer. In embodiments, silicone oil comprises a straight-chained polydimethylsiloxane fluid. In embodiments, silicone oil is a straight-chained polydimethylsiloxane fluid. In embodiments, silicone oil is a mixture of different siloxane polymers. In embodiment, the polysiloxane of silicone oil may contain in addition to methyl groups, phenyl, vinyl, epoxide or amino groups. In embodiments, the polysiloxane of silicone oil contains methyl and / or phenyl groups. In embodiments, silicone oil has viscosity ranging from 10 to 100,000 cSt at 25°C where viscosity depends generally on molecular weight of the polysiloxane. In embodiments, silicone oil has viscosity ranging from 10-1000 cST or 100 to 500 cST. In preferred embodiments, silicone oil has viscosity ranging from 250-450 cSt or 315 to 385 cSt. In more preferred embodiments, silicone oil has viscosity ranging from 325 to 375 cSt. In embodiments, the silicone oil has viscosity of 350 cSt.

[0102] Poly(vinyl alcohol) is a water-soluble polymer of general formula [CH2-CH(OH)]n. PVA is typically formed by hydrolysis of poly(vinylacetate). PVA can be prepared in a range of Mw (weight average molecular weight) and with a range of percent hydrolysis. In embodiments, PVA can range in Mw from 5000 D to 200,000 D. In embodiments, PVA can have a range of 70% or higher hydrolysis. A PVA which is 70% hydrolyzed retains 30% of the acetyl groups of the poly(vinylacetate) from which it is formed. For use in this invention, PVA can range most generally in Mw from 5000 D to 200,000 D and any subrange thereof. Useful PVA can range in Mw from 25,000 to 150,000 D, or 50,000 to 150,000 D, or 75,000 to 150,000 D or 100,000 to 150,000 D or any subranges thereof. Useful PVA can also range in Mw from 10,000 to 100,000 D, or 25,000 to 100,000 D or 50,000 to 100,000 D or 75,000 to 100,000 D or subranges thereof. Preferred for this invention are PVA ranging in Mw from 85,000 to 124,000 D. More preferred for this invention are PVA ranging in Mw from 89,000 to 98,000 D. In embodiments, PVA has a degree of hydrolysis of 70% or more. In embodiments, PVA has a degree of hydrolysis of 80% or more. In embodiments, PVA has a degree of hydrolysis of 90% or more. In preferred embodiments, PVA has a degree of hydrolysis of 95% or more. In more preferred embodiments, PVA has a degree of hydrolysis of 99% or more. As is known in the art, the solubility of PVA in a given aqueous solution depends upon the Mw and degree of hydrolysis of the PVA. One of ordinary skill in the art can without undue experimentation select an aqueous solution (including water) in which a selected amount of PVA of selected Mw and selected degree of hydrolysis is soluble.

[0103] In embodiments, the silane-based crosslinking agent is an organosilane of formula I: Ri R2R3-Si-X,where: each X is independently Cl, alkoxy, or acyloxy (-O-CO-R), where R is an optionally substituted alkyl group, an optionally substituted cycloalkyl group or an optionally susbtituted aryl group; each R-i is independently, hydrogen, an optionally susbstituted alkyl group, a optionally substituted cycloalkyl group, an optionally substituted alkenyl group, an optionally substituted aryl group, an optionally substituted alkoxy group, an optionally substituted acyloxy group or a siloxane group of formula:-O-Si-(R4)3;R2is Ri or X;R3is Ri or X; and each R4independently is an optionally substituted alkyl group, a optionally substituted cycloalkyl group, an optionally substituted alkenyl group, an optionally substituted alkoxy group or an optionally substituted aryl group.

[0104] In embodiments, alkyl and alkoxy groups independently have 1-10 carbon atoms, 1-6 carbon atoms or 1-3 carbon atoms. In embodiments, alkenyl groups have 2-20 carbon atoms, 2-6 carbon atoms or 2-4 carbon atoms. In embodiments, cycloalkyl groups have 3-12 carbon atoms. In embodiments, cycloalkyl groups have a 3-10 member carbon ring. In embodiments, cycloalkyl groups have a 5 or 6-member carbon ring. In embodiments, aryl groups have 1-3 aromatic rings. In embodiments, aryl groups have at least one 6-member aromatic ring or at least one 5-member aromatic ring. In embodiments, aryl groups have 6-18 carbon atoms, or 6-12 carbon atoms. In embodiments, aryl groups have one aromatic ring or two fused aromatic rings. In embodiments, aryl groups have two rings bonded through a single bond. In embodiments, aryl groups have three fused rings.

[0105] In embodiments, the acyloxy group has 2-12 carbon atoms, or 2-7 carbon atoms or 2-4 carbon atoms. In embodiments, acyloxy groups are acetyloxy groups.

[0106] In embodiments, optional substitution for alkyl groups is one or more optionally substituted phenyl, one or more optionally substituted benzyl groups, one or more optionally substituted cycloalkyl groups having 3-12 carbon atoms (particularly a cyclohexyl or cylopenty group) or one or more optionally substituted alkenyl groups having 2-4 carbon atoms. In embodiments, optional substitution for cycloalkyl groups is one or more optionally substituted alkyl groups having 1- 3 carbon atoms, one or more optionally substituted alkenyl groups having 2-4 carbon atoms, one or more optionally substituted alkoxy groups having 1-3 carbon atoms, one or more optionally substituted phenyl groups, or one or more optionally substituted benzyl groups.

[0107] In embodiments, optional substitution for alkenyl groups is one or more optionally substituted alkyl groups having 1-3 carbon atoms, one or more optionally substituted alkoxy groupshaving 1-3 carbon atoms, one or more optionally substituted cycloalkyl groups (particularly a cyclohexyl or cylopenty group), one or more optionally substituted phenyl groups, or one or more optionally substituted benzyl groups.

[0108] In embodiments, optional substitution for alkoxy groups is one or more optionally substituted alkyl groups having 1-3 carbon atoms, one or more optionally substituted alkenyl groups having 2-4 carbon atoms, one or more optionally substituted cycloalkyl groups (particularly a cyclohexyl or cylopenty group), one or more optionally substituted phenyl groups, or one or more optionally substituted benzyl groups.

[0109] In embodiments, optional substitution for acyloxy groups is one or more optionally substituted phenyl, one or more optionally substituted benzyl groups, one or more optionally substituted cycloalkyl groups having 3-12 carbon atoms (particularly a cyclohexyl or cylopenty group) or one or more optionally substituted alkenyl groups having 2-4 carbon atoms.

[0110] In embodiments, R is an unsubstituted alkyl group having 1 to 3 carbon atoms, an unsubstituted phenyl group or an unsubstituted benzyl group. In embodiments, R is a phenyl or benzyl group substituted with one or more alkyls having 1-3 carbon atoms, one or more alkenyl having 2-4 carbon atoms, or one or more alkoxy having 1-3 carbon atoms. In embodiments, R is an alkyl or cycloalkyl substituted with one or more optionally substituted phenyl or benzyl groups. In embodiments, R is an alkyl substituted with one or more optionaly substituted alkoxy groups having 1-3 carbon atoms. In embodiments, R is a cycloalkyl substituted with one or more optionally substituted alky groups having 1-3 carbon atoms or oen or more optionally substituted alkoxy groups having 1-3 carbon atoms.

[0111] In embodiments, variable groups of the organosilane crosslinking agent can be substituted with one or more substituent groups that is not hydrolyzed on contact with water. In embodiments, variable groups of the organosilane crosslinking agent are not substituted with any fluorines. In embodiments, carbon containing variable groups of the organosilane crosslinking agent (e.g., alkyl groups, alkoxy groups, cycloalkyl groups, alkenyl groups, acyloxy groups and aryl groups are not substituted with any halogen.

[0112] In embodiments, optionally substitution of alkyl groups includes substitution with one or more Cl, OH, -COR’, -COOR’, -OR’, or -N(R’)2, where R’ is hydrogen or an alkyl group. In embodiments, alkyl groups and aryl groups are unsubstituted. In embodiments, alkyl groups are methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl or t-butyl groups. In embodiments, alkyl groups are aryl alkyl groups including benzyl or phenethyl groups, which may be substituted or unsubstituted. In embodiments, aryl groups are phenyl groups, biphenyl groups, or naphthyl groups.

[0113] In embodiments X is alkoxy or Cl. In embodiments, X is methoxy, ethoxy or Cl. In embodiments, X is Cl. In embodiments, R2and R3are both X. In embodiments, R2is X and R3is Ri. In embodiments, each of R2, R3and X are alkoxides. In embodiments, each of R2, R3and X are Cl.

[0114] In embodiments, Ri is an alkyl group having 1-6 carbon atoms or is a cycloalkyl having 3-8 carbon atoms. In embodiments, Ri is methyl, ethyl, iso-propyl or n-propyl or Ri is cyclopentyl or cyclohexyl. In embodiments, Ri is phenyl or benzyl.

[0115] In embodiments, X is acetyloxy. In embodiments, R2and X are acetyloxy. In embodiments R2and R3and X are acetyloxy. In embodiments, each of R1-R3 and X are acetyloxy. In embodiments, X is acetyloxyl and Ri is an alkyl or aryl group.

[0116] In embodiments, Ri is a group other than a siloxane group.

[0117] In embodiments, the silane crosslinking agent does not contain fluorine. In embodiments, the silane crosslinking agent is a trichlorsilane, a triacetyloxysilane or a trialkoxysilane. In embodiments, the silane crosslinking agent is n-propyltrichlorosilane, methyltrichlorosilane, ethyltrichlorosilane, n-butyltrichlorsilane, phenyltrichlorosilane, benzyltrichlorsilane, vinyltrichlorosilane or cyclohexyltrichlorosilane or a combination thereof. In embodiments, the silane crosslinking agent is n-propyltrichlorosilane, methyltrichlorosilane, ethyltrichlorosilane, n-butyltrichlorsilane, phenyltrichlorosilane, benzyltrichlorsilane, vinyltrichlorosilane or cyclohexyltrichlorosilane. In embodiments, the silane crosslinking agent is trimethyoxysilane, triethoxysilane, or triacetyloxysilane. In embodiments, the silane crosslinking agent is phenyltrialkoxysilane, vinyltrialkoxysilane, or cyclohexyltrialkoxy silane. In embodiments, the silane crosslinking agent is phenyltrimethoxysilane, vinyltrimethoxysilane, or cyclohexyltrimethyoxysilane. In embodiments, the silane crosslinking agent is phenyltriethoxysilane, vinyltriethoxysilane, or cyclohexyltriethyoxysilane. In embodiments, the silane crosslinking agent is methyltriacetyloxysilane, ethyltriacetyloxysilane, vinyltriacetyloxysilane, n- propyltriacetyloxysilane or phenyltriacetyloxysilane.

[0118] In embodiments X is alkoxy or Cl. In embodiments, X is methoxy, ethoxy or Cl. In embodiments, X is Cl. In embodiments, R2and R3are both X. In embodiments, R2is X and R3is Ri. In embodiments, each of R2, R3and X are alkoxides. In embodiments, each of R2, R3and X are Cl.

[0119] In embodiments, Ri is an alkyl group having 1-6 carbon atoms or is a cycloalkyl having 3-8 carbon atoms. In embodiments, Ri is methyl, ethyl, iso-propyl or n-propyl or Ri is cyclopentyl or cyclohexyl. In embodiments, R-i is phenyl or benzyl.

[0120] In embodiments, X is acetyloxy. In embodiments, R2and X are acetyloxy. In embodiments R2and R3and X are acetyloxy. In embodiments, each of RI-R3and X are acetyloxy. In embodiments, X is acetyloxyl and Ri is an alkyl or aryl group.

[0121] In embodiments, Ri is a group other than a siloxane group.

[0122] In embodiments, the silane crosslinking agent does not contain fluorine.

[0123] The LIS herein can in general be formed on any surface that comes in contact with a biological fluid and that needs protection from fouling by that biological fluid. In particular, the LIS herein can be applied to or formed on a surface (or a portion of a surface) of any article or device that is or may be exposed to a biological fluid. Articles include, for example, fluid conduits (e.g., pipes or tubes), seals (flanges, o-rings and the like), optical articles (lens and the like), medical devicesinserted and retained in the body. The surface to which the LIS is applied or on which it is formed can in general be any material, typically a material that can be safely employed in applications in contact with biological fluids, including various ceramics, plastics, glass, quartz or various metals.

[0124] In embodiments, PVA and silicone oil useful in the invention are available from commercial sources. In embodiments, PVA having desired Mw and % hydrolysis can be prepared by methods known in the art by, for example, known methods of hydrolysis of poly(vinyl acetate). Silane crosslinking agents of formulas herein are available from commercial sources or can be prepared by one of ordinary skill in the art by known methods or routine adaptation of such known methods.

[0125] PVA solutions are generally prepared in aqueous solvent using distilled water or deionized water. In embodiments, PVA solutions are prepared in water. Dependent upon the application of the films and lubricated films, higher purity water (e.g., ultra pure water which has a resistivity of 18.2 MQ-cm and a conductivity of 0.055 pS / cm at 25°C) can be employed in film preparation. Any known method of water purification can be employed as needed or desired. Water employed in the methods should exclude contaminants that would be detrimental to film formation. In embodiment, the water can be treated by reverse osmosis. In embodiments, the pH of the water can range from 6-8. In embodiments, the pH of the water can be selected to a desired value. In embodiments, an aqueous solution, such as buffered water at a selected pH can be employed.

[0126] In embodiments, PVA solutions can be prepared in miscible mixtures of water and alkyl alcohol, particularly ethanol or isopropanol. In embodiments, addition of low amounts of alcohol (e.g., less than 10% by volume (or less than 5% or 1% by volume) to solutions of PVA in water can be used to adjust drying rate, film-forming behavior, or compatibility with other components (such as silane crosslinking agents).

[0127] The invention also relates to methods for making a silane-crosslinked PVA film. In embodiments, films are formed by casting of aqueous solutions containing one or more polymers and one or more silane crosslinking agents. The films can be cast on any appropriate substrate that does not interfere with film casting. Films can be cast on suitable plastic, ceramic, glass, metal or other surfaces. Aqueous solutions of PVA to which crosslinking agent has been added are cast on to the selected surface and solvent (e.g., water) is removed to form the film. In embodiments, films are formed by deposition of one or more spray-coat layers of film-forming solution on any appropriate substrate that does not interfere with spray-coating. Spray-coating, as is known in the art, can be performed, for example, using a compressed gas (e.g., compressed air) spray gun of selected nozzle diameter. Such a spray gun can be operated at appropriate compressed air pressures (e.g., 30-45 psi). Gong et al.

[0087] provides an exemplary spray-coating method. It will be appreciated that appropriate surface preparation, e.g., cleaning, may be required before forming the film on the selected surface.

[0128] A selected amount of silane crosslinking agent is added to a selected amount of PVA dissolved in aqueous solvent or water. The Mw and hydrolysis% of the PVA is selected based on theapplication of the film. The silane crosslinking agent is a compound of formula I as defined herein. One or a mixture of more than one (e.g., two) silane crosslinking agents can be added to the aqueous solution of PVA. The amount and type of silane crosslinking agent can be selected to obtain desired properties of the resultant film as shown in the examples herein. In general, the amount of silane crosslinking agent added with be 30% or less by volume of the volume of PVA solution. In preferred embodiments, the amount of silane crosslinking agent added is 20% or less by volume of the volume of the PVA solution. In embodiments, the silane crosslinking agent is added to the PVA solution slowly with vigorous mixing to limit the amount of self-polymerization of the silane crosslinking agent. In embodiments, the silane crosslinking agent is added to the PVA solution so that the silane crosslinking agent is sufficiently dilute in the PVA solution to limit the amount of self-polymerization of the silane crosslinking agent.

[0129] The amount of PVA dissolved in the aqueous solution can be varied generally between 5 to 30% wt / v of PVA in aqueous medium (water). In embodiments, the solution contains 6-18% wt / v PVA. In embodiments, the solution contains 10-14% by weight PVA. In embodiments, the solution contains 11-13% by weight PVA. In embodiments, the solution is heated to a temperature between 50°C to 70 °C to dissolve PVA. The temperature and length of heating can be varied to dissolve the PVA.

[0130] In embodiments, the addition of silane crosslinking agent to the PVA solution is performed at or near room temperature and the mixture is thereafter heated to a temperature of 50 °C to 90 °C for a sufficient time to allow crosslinking. In embodiments, the mixture is heated to a temperature between 70 °C to 80 °C for 3-24 hours or 3-6 hours.

[0131] In embodiments, the heated mixture is cooled to about room temperature and is cast on a selected substrate to form a crosslinked PVA film. The amount of film-forming solution cast on the substrate is selected to achieve a selected film thickness on the selected substrate. In embodiments, film-forming solution is cooled to near room temperature and spray-coated on the substrate. Spray-coating conditions are adjusted to achieve a selected film thickness and / or multiple spray-coating layers are applied to the surface. In embodiments, film thickness can range from 10 to 1000 microns. In embodiments, film thickness can range from 100 to 500 microns. In embodiments, film thickness can range from 200 to 500 microns. In embodiments, film thickness can range from 350 to 500 microns. In embodiments, film thickness can range from 350 to 450 microns. The selected substrate, such as a plastic or glass container, can function as a mold for film formation. After casting, water is removed from the solution to form the film. In embodiments, the film is self-supporting. In embodiments, the film is not self-supporting and is supported on a selected substrate. In embodiments, the film is dried under ambient temperature (around room temperature) and pressure (ambient air pressure). In embodiments, the temperature can be raised or vacuum applied to facilitate or assist drying (removal of water). In embodiments, the film can be formed on a surface of an article that is to be protected by the film.

[0132] It will be appreciated by one of ordinary skill in the art that films of the invention can be prepared by methods other than casting. Any known method that allows film formation from a polymer solution can be employed in the methods of this invention.

[0133] The invention provides a method of making LIS films in which a lubricant is infused into a silane-crosslinked PVA film of this invention. In embodiments, the LIS film is formed by infusing silicone oil into the silane-crosslinked PVAfilm. In embodiments, a selected amount of silicone oil is placed in contact with the silane-crosslinked PVAfilm to be absorbed into the film. In embodiments, the amount of silicone oil is in excess of what is expected to be absorbed into the film. The amount of silicone oil adsorbed into a given silane-crosslinked film can be determined by lubricant retention assays as described herein.

[0134] The excess amount of silicone oil remains in contact with the film for a sufficient time to allow the silicone oil to absorb into the film. Lubricant absorption into the film is typically conducted at about room temperature for 12-24 hours. The specific time required for optimal absorption into a given film can be determined by routine experimentation. After absorption of silicone oil into the film, excess silicone oil is removed from the film. In an embodiment, the film is held at a specific tilt angle of 45° to allow excess silicone oil to drain from the film. In an embodiment, the film is held at this tilt angle for 2-24 hours (or more specifically for 2-12 or 2-6 hours) to remove excess silicone oil. Again the time needed to remove excess lubricant from the film can be assessed by routine experimentation. In an embodiment, infusion is carried out at about room temperature. In an embodiment, removal of excess lubricant is carried out at about room temperature. The lubricant infused silane crosslinked films can be stored at about room temperature without humidity control. If desired, the lubricant infused films can be stored for future use in a sealed container with or without humidity control.

[0135] The amount of silicone oil absorbed into the LIS at a given time in contact with the silicone oil can be determined by measuring the weight increase of the film after absorption of silicone oil for a given time and subtracting the weight of the film prior to any absorption of silicone oil. The time allowed for absorption of silicone oil into a silane crosslinked film can be varied to increase the amount of silicone oil absorbed. In embodiments, the time allowed for absorption of silicone oil will be time that results in a maximum absorption of silicone oil. In embodiments, the amount of silicone oil absorbed into a silane crosslinked film to form a LIS ranges from 0.01% to 2% by weight of the film. In embodiments, the amount of silicone oil absorbed into a silane crosslinked film to form a LIS ranges from 0.01% to 1% by weight of the film. In embodiments, the amount of silicone oil absorbed into a silane crosslinked film to form a LIS ranges from 0.01% to 0.1% by weight of the film.

[0136] The invention provides a method of preventing biofouling of an article surface or a device surface that contacts, remains in contact with or which will potentially contact a biological fluid. The method involves providing a lubricant-infused silane-crosslinked PVA film surface on the surfaceof the article or device that may or does contact the biological fluid. The LIS is any lubricated silane- crosslinked PVA film as described herein which may be prepared by the methods described herein.

[0137] Technical terms used herein, in particular the names of chemical groups, generally take their broadest known meaning in the art. In embodiments, the chemical group names herein have the following meanings:

[0138] The terms alkyl or alkyl group refer to a monoradical of a straight-chain or branched saturated hydrocarbon. In general, alkyl groups include cycloalkyl groups. Alkyl groups include straight-chain and branched alkyl groups. Unless otherwise indicated alkyl groups have 1-20 carbon atoms (C1-C20 alkyl groups) and preferred are those that contain 1-10 carbon atoms (C1-C10 alkyl groups) and more preferred are those that contain 1-6 carbon atoms (C1-C6 alkyl groups) and those that contain 1-3 carbon atoms (C1-C3 alkyl groups). Alkyl groups are optionally substituted with one or more non-hydrogen substituents as may be described herein. Alkyl groups herein include those that ate unsubstituted. Exemplary alkyl groups include methyl, ethyl, n-propyl, iso-propyl, n-butyl, s- butyl, t-butyl, n-pentyl, branched-pentyl, n-hexyl, branched hexyl, including all isomers thereof and all of which are optionally substituted.

[0139] Cycloalkyl groups include those which have 1 ring or which are bicyclic or tricyclic and which have 3-20 carbon atoms (or 3-10 or 3-6 carbon atoms). In specific embodiments, cycloalkyl groups have 1 ring having 3-8 carbon atoms in the ring and preferably have 5 or 6 ring carbon atoms. Cycloalkyl groups include, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cyclooctyl groups, including all isomers thereof and all of which are optionally substituted

[0140] Alkenyl groups include monovalent straight-chain, branched and cyclic alkenyl groups which contain one or more carbon-carbon double bonds. Unless otherwise indicated, alkenyl groups include those having from 2 to 20 carbon atoms. Alkenyl groups include those having 2 to 4 carbon atoms, those having from 2-8 carbon atoms, and those having 5-8 carbons. In embodiments, alkenyl groups have one double bond.

[0141] Cyclic alkenyl (cycloalkenyl) groups include those having one or more rings wherein at least one ring contains a double bond. Cyclic alkenyl groups include those which have 1 , 2 or 3 rings wherein at least one ring contains a double bond. Cyclic alkenyl groups also include those having 3- 10 carbon atoms. Cyclic alkenyl groups include those having a 5-, 6-, 7-, 8-, 9- or 10-member carbon ring and particularly those having a 5- or 6-member ring. The carbon rings in cyclic alkenyl groups can also carry straight-chain or branched alkyl or alkenyl group substituents. Cyclic alkenyl groups can include bicyclic and tricyclic alkyl groups wherein at least one ring contains a double bond.

[0142] Alkenyl groups are optionally substituted with one or more non-hydrogen substituents as described herein. Specific alkenyl groups include ethylene (ethenyl or vinyl), propenyl, cyclopropenyl, butenyl, cyclobutenyl, pentenyl, pentadienyl, cyclopentenyl, cyclopentadienyl, hexylenyl, hexadienyl, cyclohexenyl, cyclohexadienyl, including all isomers thereof and all of which are optionally substituted.

[0143] An alkoxy group is an alkyl group (including cycloalkyl), as broadly discussed above, linked to oxygen, a monovalent -O-alkyl group. An aryloxy group is an aryl group, as discussed below, linked to an oxygen, a monovalent -O-aryl.

[0144] Aryl groups include groups having one or more 5- or 6-member aromatic rings. Aryl groups can contain one, two or three, 6-member aromatic rings. Aryl groups can contain two or more fused aromatic rings. Aryl groups can contain one, two or three aromatic rings linked by single bonds. Aryl groups can contain two or three fused aromatic rings. Aryl groups are optionally substituted with one or more non-hydrogen substituents. Substituted aryl groups include among others those which are substituted with alkyl or alkenyl groups, which groups in turn can be optionally substituted. Specific aryl groups include phenyl groups, biphenyl groups, and naphthyl groups, all of which are optionally substituted as described herein.

[0145] Alkylaryl groups are aryl groups substituted with one or more alkyl groups wherein the alkyl groups optionally carry additional substituents and the aryl groups are optionally substituted. Specific alkylaryl groups are alkyl-substituted phenyl groups such as methylphenyl.

[0146] Arylalkyl groups are alkyl groups substituted with one or more aryl groups, typically one aryl group. The aryl group is optionally substituted. Specific arylalky groups include benzyl, optionally substituted benzyl, phenethyl, and optionally substituted phenethyl.

[0147] An acyloxy group is an R’-CO-O- group where R’ in general is a hydrogen, an alkyl, alkenyl or aryl group as described above. In specific embodiments, acyloxy groups have 1-20, 1-12 or 1-6 carbon atoms optionally one double bond. In specific embodiments, R’ is a C1-C6 alkyl or an aryl group. Specific aryl groups include phenyl, benzyl, biphenyl and naphthyl. Examples include acetyloxy. Examples include acyl oxy where R’ is ethyl, n-propyl, isopropyl, n-butyl or the like. The R’ group of acyl groups are optionally substituted as described herein.

[0148] The number of carbon atoms in a given group, such as an alkyl group, can be indicated herein using the expression “Cm” where m is the number of carbon atoms. Thus, the expression “Cm1-Cm2” modifying a given chemical group indicates that the group can contain from ml to m2 carbon atoms. For example, a C1-C6 alkyl group contains 1 to 6 carbon atoms, exclusive of carbons in any substituent on the alkyl group. Similar expressions can be used to indicate the number of atoms of N (nitrogen), O (oxygen) or other elements in a given group.

[0149] Groups herein are optionally substituted most generally with one or more alky, alkenyl, alkynyl, and aryl, heteroaryl, carbocyclyl, and heterocyclyl groups can be substituted, for example, with one or more oxo group, thioxo group, halogen, nitro, cyano, cyanate, azido, thiocyano, isocyano, isothiocyano, sulfhydryl, hydroxyl, alkyl, alkoxy, alkenyl, alkenyloxy, alkynyl, alkynyloxy, aryl, aryloxy, heteroaryl, heteroaryloxy, carbocyclyl, carbocyclyloxy, heterocyclyl, heterocyclyloxy, alkylthio, alkenylthio, alkynylthio, arylthio, thioheteroaryl, thioheteroaryl, thiocarbocyclyl, thioheterocyclyl, - CORs, -COH, -OCORs, -OCOH, -CO-ORs, -CO-OH, -CO-O-CO-Rs, -CON(Rs)2, -CONHRs, -CONH2, -NRs-CORs, -NHCORs, -NHRs, -N(Rs)2, -O-SO2-Rs, -SO2-Rs, -SO2-NHRs, -SO2-N(Rs)2, -NRs-SO2-Rs, -NH-SO2-Rs,-NRsCO-N(Rs)2, -NH-CO-NHRS, -O-PO(ORS)2, -O-PO(ORS)(N(RS)2), -O- PO(N(RS)2)2, -N-PO(ORS)2, -N-PO(ORS)(N(RS)2), -P(RS)2, -B(OH)2, -B(OH)(ORs), -B(ORs)2, where each Rs independently is an organic group and more specifically is an alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, or heterocyclyl group or two Rs within the same substituent can together form a carbocyclic or heterocyclic ring having 3 to 10 ring atoms. Organic groups of non-hydrogen substituents are in turn optionally substituted with one or more halogens, nitro, cyano, isocyano, isothiocyano, hydroxyl, sulfhydryl, haloalkyl, hydroxyalkyl, amino, alkylamino, dialkylamino, arylalkyl, unsubstituted alkyl, unsubstituted alkenyl, unsubstituted alkynyl alkylalkenyl, alkylalkynyl, haloaryl, hydroxylaryl, alkylaryl, unsubstituted aryl, unsubstituted carbocylic, halo-substituted carbocyclic, hydroxyl-substituted carbocyclic, alkyl-substituted carbocyclic, unsubstituted heterocyclic, unsubstituted heteroaryl, alkyl-substituted heteroaryl, or alkyl-substituted heterocyclic. In specific embodiments, Rs groups of substituents are independently selected from alkyl groups, haloalkyl groups, phenyl groups, benzyl groups and halo-substituted phenyl and benzyl groups. In specific embodiments, non-hydrogen substituents have 1-20 carbon atoms, 1-10 carbon atoms, 1-7 carbon atoms, 1-5 carbon atoms or 1-3 carbon atoms. In specific embodiments, non-hydrogen substituents have 1-10 heteroatoms, 1-6 heteroatoms, 1-4 heteroatoms, or 1 , 2, or 3 heteroatoms. Heteroatoms include O, N, S, P, B and Se and preferably are O, N or S. Substitution with fluorine is not preferred.

[0150] In specific embodiments, optional substitution is substitution with 1-12 (or 1-3 or 1 to 3 or 1 to 6) non-hydrogen substituents. In specific embodiments, optional substitution is substitution with 1-6 non-hydrogen substituents. In specific embodiments, optional substitution is substitution with 1-3 non-hydrogen. In embodiments, optional substitution of a given group is substitution with one substituent. In specific embodiments, optional substituents contain 6 or fewer carbon atoms. In specific embodiments, optional substitution is substitution by one or more halogen, hydroxyl group, cyano group, oxo group, thioxo group, unsubstituted C1-C6 alkyl group or unsubstituted aryl group. In specific embodiments, optional substation is substitution with an unsubstituted phenyl or an unsubstituted benzyl group.

[0151] In specific embodiments, non-hydrogen substituents for optional substitution include alkyl, alkoxy, halogen (Cl, Br or I and preferably Cl), haloalkyl, or haloalkoxy. In specific embodiments, non-hydrogen substituents for optional substitution include methyl, ethyl, methoxy, ethoxy, phenyl and benzyl.

[0152] Specific substituted alkyl groups include haloalkyl groups, particularly trihalomethyl groups and specifically those where the halogen is Cl. Specific substituted aryl groups include mono-, di-, tri, tetra- and pentahalo-substituted phenyl groups; mono-, di, tri-, tetra-, penta-, hexa-, and hepta- halo-substituted naphthalene groups; 3- or 4-halo-substituted phenyl groups, 3- or 4-alkyl-substituted phenyl groups, 3- or 4-alkoxy-substituted phenyl groups, 3- or 4-RsCO-substituted phenyl, 5- or e- halo-substituted naphthalene groups. More specifically, substituted aryl groups include acetylphenyl groups, particularly 4-acetylphenyl groups as well as acetyloxyphenyl groups, particularly 4-acetyloxyphneyl groups, fluorophenyl groups, particularly 3-fluorophenyl and 4-fluorophenyl groups; chlorophenyl groups, particularly 3-chlorophenyl and 4-chlorophenyl groups; methylphenyl groups, particularly 4-methylphenyl groups, and methoxyphenyl groups, particularly 4-methoxyphenyl groups.

[0153] As to any of the above groups which contain one or more substituents, it is understood, that such groups do not contain any substitution or substitution patterns which are sterically impractical and / or synthetically non-feasible. In addition, the compounds of this invention include all stereochemical isomers arising from the substitution of these compounds.

[0154] Compounds of the invention may contain chemical groups (acidic or basic groups) that can be in the form of salts. Exemplary acid addition salts include acetates (such as those formed with acetic acid or trihaloacetic acid, for example, trifluoroacetic acid), adipates, alginates, ascorbates, aspartates, benzoates, benzenesulfonates, bisulfates, borates, butyrates, citrates, camphorates, camphorsulfonates, cyclopentanepropionates, digluconates, dodecylsulfates, ethanesulfonates, fumarates, glucoheptanoates, glycerophosphates, hemisulfates, heptanoates, hexanoates, hydrochlorides (formed with hydrochloric acid), hydrobromides (formed with hydrogen bromide), hydroiodides, 2-hydroxyethanesulfonates, lactates, maleates (formed with maleic acid), methanesulfonates (formed with methanesulfonic acid), 2-naphthalenesulfonates, nicotinates, nitrates, oxalates, pectinates, persulfates, 3-phenylpropionates, phosphates, picrates, pivalates, propionates, salicylates, succinates, sulfates (such as those formed with sulfuric acid), sulfonates (such as those mentioned herein), tartrates, thiocyanates, toluenesulfonates such as tosylates, undecanoates, and the like.

[0155] Exemplary basic salts include ammonium salts, alkali metal salts such as sodium, lithium, and potassium salts, alkaline earth metal salts such as calcium and magnesium salts, salts with organic bases (for example, organic amines) such as benzathines, dicyclohexylamines, hydrabamines [formed with N,N-bis(dehydro-abietyl)ethylenediamine], N-methyl-D-glucamines, N- methyl-D-glucamides, t-butyl amines, and salts with amino acids such as arginine, lysine and the like. Basic nitrogen-containing groups may be quaternized with agents such as lower alkyl halides (e.g., methyl, ethyl, propyl, and butyl chlorides, bromides and iodides), dialkyl sulfates (e.g., dimethyl, diethyl, dibutyl, and diamyl sulfates), long chain halides (e.g., decyl, lauryl, myristyl and stearyl chlorides, bromides and iodides), aralkyl halides (e.g., benzyl and phenethyl bromides), and others.

[0156] Salts of the invention include “pharmaceutically acceptable salts” which refers to those salts which retain the biological effectiveness and properties of the free bases or free acids, and which are not biologically or otherwise undesirable. Pharmaceutically acceptable salts comprise pharmaceutically-acceptable anions and / or cations.

[0157] Compounds of the present invention, and salts thereof, may exist in their tautomeric form, in which hydrogen atoms are transposed to other parts of the molecules and the chemical bonds between the atoms of the molecules are consequently rearranged. It should be understood that all tautomeric forms, insofar as they may exist, are included within the invention.

[0158] Additionally, inventive compounds may have trans and cis isomers and may contain one or more chiral centers and therefore exist in enantiomeric and diastereomeric forms. The invention includes all such isomers, as well as mixtures of cis and trans isomers, mixtures of diastereomers and racemic mixtures of enantiomers (optical isomers). When no specific mention is made of the configuration (cis, trans or R or S) of a compound (or of an asymmetric carbon), then any one of the isomers or a mixture of more than one isomer is intended. The processes for preparation can use racemates, enantiomers, or diastereomers as starting materials. When enantiomeric or diastereomeric products are prepared, they can be separated by conventional methods, for example, by chromatographic or fractional crystallization. The inventive compounds may be in the free or hydrate form. With respect to the various compounds of the invention, the atoms therein may have various isotopic forms, e.g., isotopes of hydrogen include deuterium and tritium. All isotopic variants of compounds of the invention are included within the invention and particularly included at deuterium and13C isotopic variants. It will be appreciated that such isotopic variants may be useful for carrying out various chemical and biological analyses, investigations of reaction mechanisms and the like. Methods for making isotopic variants are known in the art.

[0159] All references throughout this application, for example patent documents including issued or granted patents or equivalents; patent application publications; and non-patent literature documents or other source material; are hereby incorporated by reference herein in their entireties, as though individually incorporated by reference.

[0160] All patents and publications mentioned in the specification are indicative of the levels of skill of those skilled in the art to which the invention pertains. References cited herein are incorporated by reference herein in their entirety to indicate the state of the art, in some cases as of their filing date, and it is intended that this information can be employed herein, if needed, to exclude (for example, to disclaim) specific embodiments that are in the prior art. For example, when a compound is claimed, it should be understood that compounds known in the prior art, including certain compounds disclosed in the references disclosed herein (particularly in referenced patent documents), are not intended to be included in the claim.

[0161] Oustadi et al. (2025)

[0086] includes additional details of experiments described herein. For example, the reference provides additional images related to tests performed and described in the examples herein. This reference is incorporated by reference herein in its entirety for such additional details.

[0162] When a group of substituents is disclosed herein, it is understood that all individual members of those groups and all subgroups, including any isomers and enantiomers of the group members, and classes of compounds that can be formed using the substituents are disclosed separately. When a compound is claimed, it should be understood that compounds known in the art including the compounds disclosed in the references disclosed herein are not intended to be included. When a Markush group or other grouping is used herein, all individual members of thegroup and all combinations and subcombinations possible of the group are intended to be individually included in the disclosure.

[0163] Every formulation or combination of components described or exemplified can be used to practice the invention, unless otherwise stated. Specific names of compounds are intended to be exemplary, as it is known that one of ordinary skill in the art can name the same compounds differently. When a compound is described herein such that a particular isomer or enantiomer of the compound is not specified, for example, in a formula or in a chemical name, that description is intended to include each isomers and enantiomer of the compound described individual or in any combination.

[0164] One of ordinary skill in the art will appreciate that methods, device elements, starting materials, and synthetic methods other than those specifically exemplified can be employed in the practice of the invention without resort to undue experimentation. All art-known functional equivalents, of any such methods, device elements, starting materials, and synthetic methods are intended to be included in this invention. Whenever a range is given in the specification, for example, a temperature range, a time range, or a composition range, all intermediate ranges and subranges, as well as all individual values included in the ranges given are intended to be included in the disclosure.

[0165] As used herein, “comprising” is synonymous with "including," "containing," or "characterized by," and is inclusive or open-ended and does not exclude additional, unrecited elements or method steps. As used herein, "consisting of' excludes any element, step, or ingredient not specified in the claim element. As used herein, "consisting essentially of' does not exclude materials or steps that do not materially affect the basic and novel characteristics of the claim. Any recitation herein of the term “comprising”, particularly in a description of components of a composition or in a description of elements of a device, is understood to encompass those compositions and methods consisting essentially of and consisting of the recited components or elements. The invention illustratively described herein suitably may be practiced in the absence of any element or elements, limitation or limitations which is not specifically disclosed herein.

[0166] Without wishing to be bound by any particular theory, there can be discussion herein of beliefs or understandings of underlying principles relating to the invention. It is recognized that regardless of the ultimate correctness of any mechanistic explanation or hypothesis, an embodiment of the invention can nonetheless be operative and useful.

[0167] The terms and expressions which have been employed are used as terms of description and not of limitation, and there is no intention in the use of such terms and expressions of excluding any equivalents of the features shown and described or portions thereof, but it is recognized that various modifications are possible within the scope of the invention claimed. Thus, it should be understood that although the present invention has been specifically disclosed by preferred embodiments and optional features, modification and variation of the concepts herein disclosed maybe resorted to by those skilled in the art, and that such modifications and variations are considered to be within the scope of this invention.

[0168] The invention relates to a number of aspects which are listed herein:

[0169] In aspect 1 , the invention relates to a method for making a silane-crosslinked poly(vinyl alcohol) (PVA) film comprising the steps of:(a) adding a selected amount of a silane crosslinking agent to a solution of PVA to generated a film-forming solution; and(b) forming a film of the silane-crosslinked PVA on a substrate and removing solvent to form the film.

[0170] In aspect 1A, the invention relates to a method for making a silane-crosslinked poly(vinyl alcohol) (PVA) film comprising the steps of:(a) adding a selected amount of a silane crosslinking agent to an aqueous solution of PVA to generate an aqueous film-forming solution; and(b) forming a film of the silane-crosslinked PVA on a substrate and removing solvent to form the film.

[0171] In aspect 2, the invention relates to a method of making a lubricant infused PVA film which comprises the steps:(a) making a silane-crosslinked poly(vinyl alcohol) (PVA) film as in any preceding aspect; and(b) infusing the film with a selected amount of silicone oil for a time sufficient for absorption of lubricant into the silane-crosslinked poly(vinyl alcohol) (PVA) film; and(c) holding the lubricated film at a tilt angle of about 45° for a time sufficient to remove excess lubricant from the film.

[0172] In aspect 2-1 of the invention, the bulk of the lubricated film is infused with the lubricant and in aspect 2-2 more specifically the lubricant is silcon oil.

[0173] In aspect 3, the invention relates to silane-crosslinked poly(vinyl alcohol) (PVA) film.

[0174] In aspect 4, the invention relates to a lubricated silane-crosslinked poly(vinyl alcohol)(PVA) film.

[0175] In aspect 5, the invention relates to a silane-crosslinked PVA film or lubricated-infused film made a method disclosed herein.

[0176] In aspect 5, the invention relates to an article having at least one surface, at least a portion of which surface contacts a biological fluid, wherein the portion of the at least one surface is coated with a silane-crosslinked PVA film infused with silicone oil.

[0177] In aspect 6, the invention relates to a method of preventing biofouling of an article surface or a device surface that contacts (or may contact) a biological fluid which comprises providing a lubricant-infused silane-crosslinked PVA film on the surface of the article or device that contacts the biological surface. The LIS can be provided to the surface by forming the LIS on the surface (wherethe surface to be protected functions as a substrate for film formation, for example) or the LIS may be added to the surface or coated upon the surface.

[0178] In any preceding aspect, the silane-based crosslinking agent is an organosilane of formula I:RiR2R3-Si-X,I where: each X is independently Cl, alkoxy, or acyloxy (-O-CO-R), where:R is an optionally substituted alkyl group having 1 to 3 carbon atoms, an optionally substituted cycloalkyl havig 6-12 carbon atoms or an optionally substituted phenyl group; each Ri is independently, hydrogen, an optionally substituted alkyl group, an optionally substituted cycloalkyl group, an optionalluy substituted alkenyl group, an optionally substituted aryl group or a siloxane group of formula:-O-Si-(R4)3;R2is Ri or X;R3is Ri or X; and each R4independently is an optionalluy substituted alkyl group, a optionally substituted cycloalkyl group, an optionally substituted alkenyl group, an optionally substituted alkoxy group or an optionally substituted aryl group.

[0179] In any preceding aspect, the silane-crosslinking agent is an organosilane of formula I: RiR2R3-Si-X,I where: each X is independently Cl, alkoxy, or acyloxy (-O-CO-R);R is an alkyl group having 1 to 3 carbon atoms; each R-i is independently, hydrogen, an alkyl group, a cycloalkyl group, an alkenyl group, an aryl group or a siloxane group of formula:-O-Si-(R4)3;R2is Ri or X;R3is Ri or X; and each R4independently is an alkyl group, a cycloalkyl group, an alkenyl group, an alkoxy group or an aryl group.

[0180] In any preceding aspect, the amount of silane crosslinking agent added to the aqueous solution of PVA ranges from 1% to 40% vol of agent / vol. of polymer solution. In any preceding aspect, the amount of silane crosslinking agent added to the aqueous solution of PVA ranges from 5% to 20% v / v. In any preceding aspect, the amount of silane crosslinking agent added to theaqueous solution of PVA ranges from 5% to 15% v / v. In any preceding aspect, the amount of PVA dissolved in the aqueous solution ranges from 5% to 30% weight of PVA / volume. In any preceding aspect, the amount of PVA dissolved I the aqueous solution ranges from 10-15% w / v. In any preceding aspect, the PVA is dissolved in water. In any preceding aspect, the aqueous solution of PVA is formed by addition of solid PVA to the aqueous solvent at a temperature of 20-80 °C with stirring to dissolve PVA. In any preceding aspect, the PVA ranges in Mw (weight average molecular weight) from 5,000 to 200,000 D and where the PVA is 70-100% hydrolyzed (contains from 0-30% residual acetate residues). In any preceding aspect, the PVA ranges in Mw from 89,000 to 98,000 D and where the PVA is 95% or more hydrolyzed. In any preceding aspect, the aqueous solution containing silane-crosslinked PVA is heated to a temperature ranging from 50 to 70 °C for 1-12 hours prior to film formation. In any preceding aspect, the film generated ranges in thickness from 200-400 microns. In any preceding aspect, the substrate upon which the film is formed is plastic, glass, quartz or metal. In any preceding aspect, the film formed is self-supporting. In any preceding aspect, the silane-crosslinked poly(vinyl alcohol) (PVA) film is washed with water and dried prior to infusion of the silicone oil. In any preceding aspect, the lubricant is silicone oil. In any preceding aspect, the lubricant is silicone oil having viscosity of ranging from 10-1000 cSt. In any preceding aspect, the lubricant is the silicone oil is having viscosity of of 250-450 cSt. In any preceding aspect, the silicone oil is medical grade. In any preceding aspect, the biological fluid is blood, plasma, or a fluid containing one or more microorganism.

[0181] In any preceding aspect in the silane crosslinking agent, X is Cl or alkoxy. In any preceding aspect in the silane crosslinking agent, Ri is an alkyl, an alkoxyl or an aryl group. In any preceding aspect in the silane crosslinking agent, X is Cl. In any preceding aspect in the silane crosslinking agent, R2and R3are both Cl. In any preceding aspect in the silane crosslinking agent, Ri is an alkyl group having 1-6 carbon atoms. In any preceding aspect in the silane crosslinking agent, Ri is an n-propyl group. In any preceding aspect, the silane crosslinking agent, the silane- crosslinking agent is n-propyl trichlorosilane.THE EXAMPLESExample 1 : Materials and MethodsMaterials and Methods

[0182] Polyvinyl alcohol (PVA) (Mw=89,000 to 98,000) 99+> hydrolyzed, 4-(2-hydroxyethyl)-1- piperazineethanesulfonic acid (HEPES), and sodium chloride (NaCI), were obtained from Sigma- Aldrich. N-propyltrichlorosilane (n-PTCS) (98%), phosphate-buffered saline (PBS) tablets, calcium chloride (CaCI2), agar powder, Gibco Bacto yeast extract, Gibco Bacto tryptone, Tryptic soy broth, peptone and the PrestoBlue cell viability reagent were purchased from Thermo Scientific Inc. Pooled citrated plasma and human whole blood was collected from healthy donors following the established protocol described in previous studies

[0047] , Before blood collection, all donors provided written consent, and all procedures were approved by the University of Calgary Research Ethics Board (Ethics ID: REB22-1151). E. coli (ATCC 25922) was obtained from Cedralane Laboratories. GFP- tagged E. coli (25922GFP) was purchased from ATCC Co.Attenuated Total Reflectance Fourier Transform Infrared (ATR-FTIR)

[0183] Attenuated total reflection Fourier transform infrared (ATR-FTIR) Spectrometer analysis was performed using a Nicolet iS50 Spectrometer to analyze the chemical bonds in PVA and PS films in the spectral range of 500-4000 cnr1.Raman spectroscopy

[0184] Raman spectroscopic analyses of PVA and PS membranes were performed using a WITec Alpha-300 series confocal Raman microscope. The instrument was equipped with a diode laser emitting light at a wavelength of 532 nm. Measurement conditions included a laser power of 10 mW and an integration time of 10 seconds per spectrum.Powder X-ray diffraction (PXRD)

[0185] Power X-ray diffraction (PXRD) patterns of the samples were collected using a Bruker D8 Advance ECO diffractometer equipped with a Cu-Ka source (I = 1 .54178 A, kV = 40, mA = 25) and an LYNXEYE XE detector in the scan range of 29 from 10° to 80°.Thermogravimetric analysis (TGA) and Differential scanning calorimetry (DSC)

[0186] The thermal stability of the films was assessed using a thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) analyzer (Mettler Toledo Co, USA). The temperature was increased at a rate of 10°C / min, with N2flowing at 60 mL / min. The samples were positioned within aluminum pans, and gradual heating scans were conducted, spanning from 25 to 600 °C.Scanning Electron Microscope (SEM)

[0187] SEM was performed (FEI Quanta 250 FEG ESEM) on PVA and PS samples to study their surface properties after adding different concentrations of the silane crosslinking agent, e.g., n- PTCS, and to investigate the blood-plasma interactions and clot adhesion on their surfaces. For samples from blood and plasma clotting experiments, a fixation step was implemented wheresamples were immersed in 2% glutaraldehyde for 24 hours, rinsed with PBS, and dehydrated through a graded ethanol series (50%, 70%, 90%, and 100%). The fixed samples were left to air-dry for 24 hours before SEM imaging. Samples were mounted on SEM stubs using double-sided carbon tape, placed in a sputter coater (ACE600 Leica coating machine), and coated with a platinum layer.Moreover, energy-dispersive X-ray spectroscopy (EDS) (Quantax 5030 SDD, Bruker) was utilized for elemental analysis of the surfaces.Lubricant Retention Studies

[0188] To assess the ability of PS films crosslinked with different silane crosslinking agent concentrations to retain lubricant, create a lubricant-infused slippery surface, and to determine how varying the concentration of the crosslinker affects this ability, lubricant infusion over a set period of time was investigated and quantified by measuring the weight difference before and after lubrication. First, samples were weighed and then 200 pL of silicone oil was added to the surface of the samples and left to infuse overnight. The excess lubricant was removed from the surface of each sample, and they were reweighed. The weight change before and after adding the lubricant indicated the extent of lubricant infused in each sample.Tensile Strength Test

[0189] Tensile strength and elasticity of the samples were assessed by uniaxial tensile loading tests, performed with a UniVert uniaxial machine (CellScale, Canada), coupled with image-based strain measurement tools and a USB 2.0 monochrome scientific imaging camera (DMK 41 AU02). Uniaxial tests were performed using two actuators at room temperature. Initially, the samples were preloaded up to 0.1 N, then they were elongated at a rate of 5 mm / min until rupture occurred. Force and displacement data alongside sample size measurements were used to develop stress-strain curves, determining the ultimate tensile strength (UTS), elongation at UTS, and Young's modulus. Displacement during the tests was continuously monitored and recorded using the USB 2.0 monochrome scientific imaging camera (DMK 41AU02).Fatigue Resistance Test

[0190] A UniVert uniaxial machine was utilized to assess the tensile and bending fatigue resistance characteristics of all samples, employing a pre-tension of 0.5 N for 30% and -60% displacement, respectively. A dynamic uniaxial tensile load was applied over 1000 cycles using a sinusoidal function at a frequency of 0.5 Hz. The residual force was continuously monitored and recorded throughout the testing procedure.Torsional Strength Test

[0191] To investigate the flexibility of the PS samples in comparison to control PVA, a torsion (twisting) test was designed and implemented. The samples were prepared in a ribbon shape, measuring 1 x 5 cm, and securely positioned within the grips of the UniVert uniaxial machine. During each cycle, the upper grip underwent a 360-degree twist and the number of twisting cycles before reaching the point of rupture was recorded.Suture Retention Test

[0192] Suture retention strength assessments were conducted as an indicator of anastomotic strength, a key physical attribute of implants [48, 49], Within this test, a suture carefully inserted into a sample is subjected to tension, and the sample is uniaxially stretched until reaching the point of rupture. This assessment is quantified following the guidelines established by the American National Standards Institute / Association for the Advancement of Medical Instrumentation

[0050] , The test was performed using the UniVert uniaxial machine on rectangular-shaped samples (20 x 10 cm2; t=0.5 mm). The thread was passed through the samples, centered with respect to the sample width and 5 mm from the end, then fixed in upper clamps by multiple knots. A schematic is shown in U.S. provisional application 63 / 712,534 and in reference

[0065] , After the suture was pulled straight, both clamps were adjusted to apply a pulling speed of 1 mm / s until the point of failure was reached. The force (g) required to pull the suture through the sample was recorded. In addition, the samples were imaged, and an analysis of finite element strain was conducted on the images using UniVert software, to extract the local strain data. This analysis was used to generate strain heat maps. First, the images acquired during testing were tracked using a 9x9 mesh in the UniVert software and the resulting principal strains were exported to Excel. Finally, a program was developed in MATLAB R2022 to interpret the Excel data and generate the strain heat maps [49, 51], The strain heat maps are shown in U.S. provisional application 63 / 712,534 and reference

[0086] , both of which are incorporated by reference herein with respect to the heat map data.Swelling and DegradationTo determine the swelling capacity of the samples, they were cut into 1 x 1 cm2squares and weighed (w0) followed by incubation in 10 mL of PBS. After 24h, samples were taken out, gently padded using a paper towel, and reweighed (wt). The corresponding swelling ratio was defined by Equation 1

[0052] , Equation 1 : Swelling Ratio (%) = ((wt- wo) / wo)*1OO

[0193] The degradation test was conducted over a period of 4 months. Similarly, samples were incubated in 10 mL of PBS, then at each time interval, removed and air dried at room temperature, and reweighed. The percentage of weight loss was measured using Equation 2. To monitor and compare the morphological changes and deformation of the samples over time, images were captured at various time intervals throughout the degradation test. Equation 2: Weight Loss (%) = ((wt- wo) / wt)*100Contact and Sliding Angle Measurements

[0194] The water repellency and wetting properties of control PVA and PS samples were analyzed using water sliding and contact angle measurements. Static contact angle measurements were done using a rame-hart goniometer / tensiometer (model 500). A 5 pL water droplet was dispensed onto the sample and images were captured at 10-second intervals to examine the water absorption characteristics of the modified and control surfaces and the effectiveness of lubricated and non-lubricated PS samples in preventing water absorption.

[0195] To determine the sliding angles, samples were positioned on the edge of a tilting blade of a digital angle measuring device (PROSTER) and a 10 pL droplet of the test liquid (water or blood) was deposited onto their surface. The angle of the blade was incrementally increased until the droplet started to slide on the surface, and this angle was recorded as the sliding angle. In cases where the droplet did not move, a sliding angle of 90° was reported. For the droplet sliding time assessment, samples were placed on a glass slide set at a 20° angle inside a petri dish. Subsequently, 50 pL of various liquids (water, blood, or plasma) were dispensed onto the surface, and sliding duration was recorded.Blood Adhesion and Clotting Assays

[0196] The blood resistant properties of control PVA and PS10-L samples using three methods: blood clot adhesion to measure the thrombus mass adhered to each sample, blood staining, and blood clotting initial time. To quantify the adhered thrombus mass to the surfaces of control and PS10S-L samples, samples were first weighed and placed in a 48-well plate. Subsequently 200 pL of citrated whole blood was added to each well, followed by the addition of 200 pL of 20 mM HEPES containing 1 M CaCI2(achieving a 12.5 mM CaCI2concentration) to initiated blood clotting. After 2 h of incubation at 37°C, the samples were carefully removed, gently tapped on filter paper, and reweighed. The adhered blood clot mass was determined by subtracting the initial weight of each sample from its final weight.

[0197] To perform the blood staining test, samples were cut into 8 mm circles and placed in 48-well plates, followed by incubation in 500 pL of citrated human whole blood for 30 seconds at 37 °C. Subsequently, the samples were transferred to wells filled with 700 pL of deionized water and placed on a mini shaker (VWR) for 30 minutes to facilitate the removal of any adhered blood. Afterward, 200 pL of the solution of each well was transferred to a new well plate for optical density measurement using a plate reader at 450 nm (SpectraMax M2, Molecular Devices). Blank wells, containing 200 pL of deionized water, served as the control group.

[0198] An in vitro blood clotting assay was carried out to measure the blood clotting time on PVA and PS10-L samples. Briefly, calcium chloride (0.1 M) was added to the blood in a ratio of 9:1 v / v and vortexed for 10s to initiate clotting. Then, samples were placed in 24-well plates and 200 pL of recalcified blood was carefully added to each well (see Figure 6 schematic). At specific time intervals, the samples were extracted and rinsed with PBS until soluble blood components were removed. The initial indications of blood clot formation adhering to the surface of each sample were recorded as the onset of blood clotting.Plasma Clotting Assay

[0199] In addition to the blood clotting test, a plasma clotting assay was carried out to investigate the anticoagulant properties of the samples. PS10-L and PVA samples were rolled and positioned in a 96-well plate. Subsequently, 100 pL of citrated plasma was added to each well, and the plate was incubated for 15 minutes at 37 °C. To initiate plasma clotting, 100 pL of pre-warmed 25mM CaCI2in HEPES was added to each well. Plasma clot formation was assessed by measuring absorbance in kinetic mode at 405 nm in 10 s intervals using a plate reader. Clotting times were determined as the duration required to reach half-maximal absorbance. Further, the samples were collected and fixed in a 2% glutaraldehyde solution and subjected to SEM analysis. Blank wells with plasma and CaCI2, without the samples, were used as controls.Bacterial Repellency Properties

[0200] For the bacterial adhesion assay, samples were cut (15 x 18 mm2), rolled, and placed in a 48-well plate. Then, 1 mL of Escherichia coli bacterial suspension (103CFU / ml) was added to each well. The plate was incubated at 37°C for 24 h. After incubation, the media was removed, and samples were washed with PBS before being transferred to a falcon tube containing 5 mL Luria- Bertani (LB) broth. The samples and broth were vortexed to detach adhered bacteria from the surfaces. Subsequently, 100 pL of the solution was used for conducting a Colony Forming Unit (CFU) assay. This involved performing ten-fold serial dilutions of the initial bacterial solution and inoculating 20 pL of the final dilution on LB agar in Petri dishes. The CFU / plate count was determined by visually inspecting the agar plates. The CFU / mL of the initial bacterial solution was calculated based on the dilution factor and the number of colonies counted on the plates, providing a quantitative measure of viable bacterial cells.

[0201] A bacterium stamping test was also conducted to evaluate the samples' resistance to bacterial transfer and adhesion. Agar plates were prepared by dissolving 1 .5% agar powder in DI water and stirring at room temperature. The agar solution was then autoclaved and poured into a petri dish to cool and solidify. An 8 mm sterile biopsy punch was used to collect agar plugs, which served as stamps. Each stamp was inoculated with 20 pL of concentrated bacterial solution (107CFU / ml) and incubated for 1 h. Following incubation, the stamps were pressed onto the sample surfaces, which were incubated for an additional hour. Next, the stamped surfaces were transferred to a microtube containing 1 mL of LB media and vortexed for 30 s to detach bacterial cells from the surfaces. From this solution, 100 pL was taken and a CFU assay was performed (Fig 7C).

[0202] To assess the blocking properties of the surfaces to bacterial migration and movement, a bacterial migration test was performed as previously described

[0032] , The procedure involved placing the ribbon-shaped samples (0.5 x 1 mm2) in the center of LB agar plates and inoculating a single bacterial colony 1 cm away from the samples. The growth and migration of E. coli colonies around and over the samples were inspected after 72h of incubation at 37°C. Subsequently, each sample was retrieved and immersed in 1 mL of the culture media. After vortexin g for 30 seconds, 100 pL of the resulting bacteria-contaminated media was diluted 100 times and 200 pL of the diluted media was inoculated onto a corresponding agar plate, and the plate's coverage was measured after 48h.Statistical Analysis

[0203] The data analysis was performed, and the results were expressed as means ± standard deviation (SD) based on a minimum of three replicates. To determine significant differences, one-way ANOVA was employed.Example 2: Preparing Lubricant-Infused PVA Films

[0204] Lubricant-infused PVA films were fabricated by initially crosslinking PVA films through solvent-casting of the PVA / n-PTCS solution followed by lubrication. Briefly, a 12% w / v PVA solution was prepared in distilled water and stirred for 2h at 80°C. Different concentrations of n-PTCS (1%, 5%, 10%, 20%, and 30% v / v) were then added to the PVA solution. The silane crosslinking agent can be added dropwise to a stirred aqueous solution of PVA. The PVA / n-PTCS solution mixture was stirred for 3h at 70°C to complete the crosslinking reaction. Afterward, a selected fixed volume of the solutions were cast into Petri dishes (5 mL of solution into 5 cm diameter plastic Petrie dishes) and dried overnight. The films generated were about 400 micron in thickness. The amount of solution added can be selected to achieve a desired film thickness in the Petrie dish used as a mold for the film. (Clearly the amount of solution added to form the film depends upon the size / shape of the mold used.) Once removed from the Petri dish molds, the films were rinsed with distilled water three times to remove any residual n-PTCS and non-crosslinked PVA molecules. Subsequently, the silane- crosslinked PVA films (PS), were infused with 200 pL of silicone oil overnight. The crosslinked PVA films (PS) were infused with 200 pL (an excess) of silicone oil overnight. The lubricated samples were kept at a 45° tilt for 3 h to remove any excess lubricant not infused into the film from the surface. Considering the concentrations of n-PTCS, samples are named PS1-L, PS5-L, PS10-L, PS20-L, and PS30-L. Pure PVA films (non-crosslinked) were used as a control group.Example 3: Microstructure and chemical characterization of the films

[0205] Lubricant-infused PVA films were fabricated by dissolving PVA in water and adding liquid n-PTCS. The alkyl trichlorosilane is a crosslinker and can also function as a hydrophobic agent. The fabrication process involved casting and subsequent lubrication through silicone oil infusion (Example 2). Before adding the lubricant layer, to optimize the crosslinking amount, various concentrations of n-PTCS (0%, 1%, 5%, 10%, 20%, and 30% v / v were added, resulting in samples with different silane cross-linker (PVA, PS1 , PS5, PS10, PS20, and PS30, respectively). The microstructural and chemical composition of the films were examined in photographs and using SEM equipped with an energy-dispersive X-ray spectrometer (EDS) (Figs. 1A and 1 B). SEM images (Fig. 1A, middle and bottom rows) revealed that PVA, PS1 , and PS5 films possess a smooth surface with minimal surface roughness. However, by increasing the concentration of the n-PTCS above 5%, the surface roughness of the films increased as illustrated in the SEM images of Fig. 1A. It is believed that increasing the concentration of silane crosslinker lead to self-polymerization of free silane crosslinker, resulting in the formation of silicon-based nano / micro-particles within the films

[0030] , Theseparticles integrated within the PVA polymer matrix, leading to the observed increased surface roughness. Moreover, by increasing the concentration of n-PTCS to 20 and 30% in PS20 and PS30 samples, respectively, there was a corresponding increase in the particle size, resulting in a nonhomogeneous structure after casting the polymeric films.

[0206] Fig. 1 B provides graphs of the elemental analysis measured by energy-dispersive X- ray spectroscopy (EDS) of control and crosslinked film samples labeled as in Fig. 1A.

[0207] The chemical structure of the samples was characterized using ATR-FTIR (Fig. 2B) and Raman spectroscopy (FIG. 8). The ATR-FTIR analysis of PVA films (Fig. 2B) displayed distinctive peaks at 1089 cm1[d] and 2923 cnr1[b], indicating the existence of stretching vibrations related to C- O and C-H bonds, respectively. A broad peak at 3273 cnr1attributed to -OH bond stretching vibrations, showed reduced intensity upon adding n-PTCS, indicating crosslinking of hydroxyl groups on the PVA backbone (Fig. 2B, [a]). Further, on increasing the n-PTCS concentration, a peak appeared in 2959 cm-1 associated with -CH2bonds (Fig. 2B, [b]),

[0042] and the absorbance of Si-CH3at 1220 cm-1 increased (Fig. 2B, [c]), consistent with the propyl (-CH2CH2CH3) group in the n-PTCS molecules. Significant changes were also observed at 999 cm-1 and 1097 cm-1 , corresponding to Si- O-C and Si-O-Si bands, respectively, when comparing PS samples with pure PVA (Fig. 2B, [d]).

[0208] These observations support the covalent crosslinking of PVA chains through the incorporation of n-PTCS molecules via a condensation reaction, as depicted in the schematic in Fig. 2A. In the crosslinking process, initially, n-PTCS molecules are believed to undergo hydrolysis in the polymer solution, reacting with water molecules and substituting the chlorine groups with hydroxyl groups, which results in the release of HCI. Subsequently, the PVA chains react with hydrolyzed n- PTCS molecules through a condensation reaction

[0043] , The FTIR results were also supported by Raman spectroscopy results shown in Fig. 8. The appearance of 490 cm-1 and 1000 cm-1 peaks in the Raman spectra, corresponding to Si-O-Si bonds, aligns with the observations from FTIR regarding the presence of Si-O-C and Si-O-Si bands in the PS samples. These bonds indicate the crosslinking of PVA chains facilitated by incorporating n-PTCS molecules. Additionally, the intensity enhancement of peaks at 2995 cm-1 and 3300 cm-1 in the Raman spectra with increasing n-PTCS concentration corresponds to the increased presence of -CH3and -CH2bonds, respectively, which is consistent with the FTIR results.

[0209] To investigate the crystalline transformation of the samples, XRD analysis was conducted (Fig. 2D). The XRD pattern of the PVA samples revealed a broad peak around 20°, showing its semi-crystalline nature

[0044] , After the addition of n-PTC, an increase in peak intensity and a reduction in peak width in the XRD pattern of PVA was observed

[0045] , This indicates that the crosslinking process promotes more ordered crystalline regions by facilitating the alignment of PVA chains, resulting in defined crystalline domains

[0044] , No additional peaks were detected in the crosslinked samples, indicating homogenous distribution of the n-PTCS within the PVA polymer matrix [46-48],Example 4: Thermal Stability of the Films

[0210] TGA and DSC analyses were conducted on both PVA (control) and PS (crosslinked) samples to investigate their thermal stability. Fig. 2E illustrates the TGA result, which can be divided into three distinct degradation phases l-lll. Phase I occurred in the temperature range of 50-150°C, related to the water evaporation, resulting in a weight loss of approximately 10% for all samples. Phase II, occurring from 200 to 400°C, with the resulting weight losses approximately 40% for PVA, PS1 , and PS5 samples, while PS10, PS20, and PS30 exhibited a reduced loss of about 20%. Phase II was associated with the continuous dehydration of the PVA polymer and the formation of polyene structures

[0049] , Phase III, related to the polymer decomposition into low-molecular-weight products

[0049] , began at about 350°C for PVA, 380°C for PS1 , 400°C for PS5 samples, and at 460°C for PS10, PS20, and PS30 samples. The shift of phase III to higher temperatures and the reduced severity of degradation in PS10, PS20, and PS30 samples compared to PVA, PS1 , and PS5 samples indicate that crosslinking with more than ~10% n-PTCS decreases the number of hydroxyl groups, resulting in reduced dehydration and altered thermal degradation profiles, thereby enhancing thermal stability [49-51],

[0211] The difference in the phase transmission temperatures can be justified in two ways. Firstly, the presence of n-PTCS and the crosslinking of the PVA polymer can lead to a reduction in the magnitudes of the decomposition in phases II and III. Secondly, the shift of phase II to higher temperatures can be attributed to the decreased number of hydroxyl groups in the crosslinked samples, resulting in reduced dehydration. Comparatively, the degradation in PS10, PS20, and PS30 samples was less severe than that in the PVA, PS1 , and PS5 samples, as evident in the TGA curves. The results indicate that the presence of more than 10% n-PTCS and the crosslinking of the PVA structure altered the thermal degradation profile and subsequently improved the thermal stability of the crosslinked films.

[0212] DSC curves for different samples are shown in Fig. 2F where the glass transition temperature (Tg) and melting temperature (Tm) values are indicated. Control PVA films exhibited a Tg of 55°C, increasing to 60°C, 70°C, 80°C, 82°C, and 82°C in PS1 , PS5, PS10, PS20 and PS30 samples, respectively. While there was no significant difference in Tg between pure PVA and PS1 samples, noticeable increases were observed starting from PS5, with the most substantial differences seen in PS10, PS20, and PS30 samples. This elevation in Tg is attributable to the crosslinking effect introduced by the silane molecule in the PVA films, leading to the mobility restriction of PVA chains. This limitation on chain movement and the transition from a glassy to a rubbery state, results in a higher Tg in crosslinked samples [52, 53], Moreover, as shown in Figure 2F, there was no significant difference in the Tm between the pure PVA and PS samples and the Tm of PVA remained stable at 165°C after crosslinking. This is due to the high thermal energy required to disrupt intermolecular bonds, which is evident even after crosslinking. Although crosslinking slightly increased thecrystallinity of PVA according to XRD results, it did not significantly alter Tm. While Tm remains relatively unchanged, the increase in Tg and crystallinity could still affect the materials overall thermal behavior and mechanical properties.Example 5: Lubricant Acquisition and Sliding and Contact Angle Measurements

[0213] To examine the effects of increasing the n-PTCS concentration on the absorption and retention of the lubricant in crosslinked PS samples, a lubricant acquisition test was conducted. The samples were weighed both before and after incubation with silicone oil. As shown in Fig. 2C, the results indicate a consistent increase in lubricant retention with increasing n-PTCS concentration. Specifically, PS30-L samples exhibited a nine-fold increase in lubricant acquisition compared to PS1- L samples (P < 0.0001), which have the least amount of crosslinker. This enhancement is attributable to the increase in the silane content in the PS films with increasing n-PTCS concentration, and the strong intermolecular interactions believed to be occurring between the silicon groups in both silicone oil and the PS films. To evaluate the wettability and water absorption properties of samples, water absorbance, static contact angle, and sliding angle measurements were conducted. As shown in Figure 3A, PVA films exhibited complete absorption of water droplets, consistent with their inherent hydrophilic nature. However, after adding n-PTCS, water droplet absorbance on PS surfaces decreased, with droplets remaining on their surfaces even after 30 min. Pure PVA films had a static contact angle of 61 ± 6.8°. The incorporation of 1%, 5%, 10%, 20%, and 30% n-PTCS increased the contact angles to 89 ± 4.8°, 101 ± 2.5°, 108 ± 1.4°, 110 ± 2.8°, and 117 ± 4.6°, respectively (Fig. 3B). Adding the lubricant to the PS samples decreased the corresponding contact angles to 78 ± 5.7°, 87 ± 5.9°, 100 ± 1.2°, 101 ± 4.5°, 109 ± 3.6° in PS1-L, PS5-L, PS10-L, PS20-L, and PS30-L samples, respectively, as expected for lubricant-infused surfaces

[0038] ,

[0214] One of the important attributes of LIS is its capacity for a sliding effect on biofluid solutions, contributing to the enhancement of its repellency properties. The slippery behavior of the lubricant-infused samples and the stability of the lubricant layer were assessed by measuring the sliding angle of a 5 pL water or blood droplet at the first day of lubrication and also after three weeks (Fig. 3C). Consistent with contact angle experiments, due to innate hydrophilic properties of PVA, water droplets were readily absorbed by PVA samples, and no slippery properties were observed in the PVA control. In contrast, slippery properties were observed in the lubricated crosslinked PVA samples, with water sliding angles of 31 ± 3°, 13 ± 3°, 8 ± 2°, 9 ± 1 °, and 7 ± 1 ° and blood sliding angles of 23± 5°, 16± 3°, 10± 1 °, 10± 2°, and 8± 2°, in PS1-L, PS5-L, PS10-L, PS20-L, and PS30-L samples, respectively. Crosslinking with the silane crosslinking agent led to an improvement in slippery properties (Fig. 3C, graph on left). This enhancement can be attributed to increased lubricant retention and higher contact angles on these surfaces

[0028] ,

[0215] To show the durability and stability of the lubricant layer, and the intermolecular interactions formed between the composite film’s surface and the lubricant layer, sliding angle measurements were also carried out three weeks after the initial lubrication. As also seen in Fig. 3C(graph on right), no significant differences in sliding angles were seen in different samples when compared to day 1 of lubrication.

[0216] PVA naturally exhibits hydrophilicity, however, when modified with nonpolar molecules such as n-PTCS, the hydrophilic and wettability properties of pure PVA undergo a significant transformation. This transformation is evident in the high static contact angles observed on the surfaces of crosslinked samples, even with just a 1% addition of the silane crosslinker. Infusion with a low-surface-tension lubricant, such as silicone oil, results in the formation of a dynamic lubricant layer, leading to the development of low sliding angles and conferring super-repellent characteristics to the lubricated crosslinked surfaces.Example 6: Swelling, and Degradation Properties

[0217] A swelling and degradation test was conducted to further evaluate the crosslinking impact on water absorption and the ability of the lubricant layer to function as a diffusive barrier. Consistent with the water absorption results, the swelling test revealed that crosslinking with n-PTCS followed by lubrication significantly reduced the swelling ratio of samples when compared to PVA (Fig. 3D). The swelling percentage of PVA was 315 ± 10%, while the PS-L samples exhibited reduced swelling percentages of 90 ± 2%, 75 ± 4%, 42 ± 2%, 37 ± 6%, and 14 ± 4% for PS1-L, PS5-L, PS10- L, PS20-L, and PS30-L, respectively (P<0.0001).

[0218] The degradation of pure PVA films in an aqueous environment is primarily influenced by solubility and water absorption. To investigate the impact of crosslinking of the PVA membrane on its degradation properties, the weight loss of films submerged in PBS at 37°C was monitored over 8 weeks, as illustrated in Figs. 3E and 3F Increasing crosslinking concentration correlated with a significant reduction in the degradation rate of the PVA films. PVA films experienced a 40 ± 2.3% weight loss over 8 weeks, which decreased to 34 ± 1 .4%, 22 ± 2.3%, 12 ± 2.8%, 9 ± 1%, and 8 ± 1.5% in the PS1-L, PS5-L, PS10-L, PS20-L, and PS30-L samples, respectively. While PS1-L and PS5-L continued to experience weight loss throughout the 8 weeks, PS10-L, PS20-L, and PS30-L stabilized after the initial week. Swelling and degradation test results indicate that the presence of the n-PTCS in the PVA composition and the lubricant layer act as a diffusion barrier, significantly enhancing the stability of the PVA films in aqueous environments. Notably, the PS10-L, PS20-L, and PS30-L samples retained their structural integrity, while observable signs of deterioration and deformation were evident in the PVA, PS1-L, and PS5-L samples. These results demonstrate that crosslinking of the PVA membrane with a silane-based crosslinking agent, such as n-PTCS, significantly enhances degradation properties of the crosslinked films.Example 7: Mechanical Properties of the Films

[0219] To evaluate the mechanical characteristics of the film samples before and after crosslinking with varying concentrations of n-PTCS, several mechanical tests were performed including, tensile stretching, tensile fatigue, bending fatigue, torsional strength (twisting), and suturesretention tests. To test the material properties under large tensile forces, uniaxial tensile tests were conducted. The stress-strain curves of the samples are shown in Fig. 4B. The Young’s modulus, elongation, and tensile strength were derived from the stress-strain curves and are presented in Figs.4C-4E. The results of the tensile tests demonstrated an enhancement in both tensile strength and elasticity by addition of increased crosslinking agent. Noteworthy is the significantly higher tensile strength observed in the PS10-L films, reaching 29 ± 1 .2 MPa, surpassing values for other samples (17.5 ± 2.2, 20.5 ± 1 , 24 ± 1.2, and 21.8 ± 0.8 MPa for PS1-L, PS5-L, PS20-L, and PS30-L, respectively). Increasing the amount of n-PTCS to 20% and 30% is believed to have made the structure brittle, possibly due to the self-polymerization of the free n-PTCS agents to form particles in these samples which acted as stress points. Notably, the elongation at the ultimate tensile strength point for PVA control samples was 36.5 ± 3.3%. With the addition of the crosslinker, the elongation significantly increased, measuring 105 ± 5.3%, 113 ± 5.3%, 177 ± 4.8%, 103 ± 5%, and 64 ± 3% for PVA, PS1-L, PS5-L, PS20-L, and PS30-L, respectively.

[0220] In addition to strength and elasticity, high fatigue resistance can be important for biomaterials, especially in numerous biomedical applications where materials experience repetitive forces. To assess a material’s behavior under repetitive loading, a variety of fatigue testing can be performed in vitro. For this assessment, bending and tensile fatigue tests were performed to investigate how the samples respond to various and repeated loading. In both bending (Fig. 4F) and tensile fatigue tests (Fig. 5A), samples were initially pre-tensioned, and their ability to maintain this initial tension was evaluated after each testing cycle to over 1000 cycles.

[0221] Results for the bending fatigue test have shown that PVA control samples experienced a 30% and 50% reduction in tension retention after 10 and 1000 cycles. In contrast, crosslinked PS samples remained robust throughout the testing, maintaining their initial tension without any significant depletion in structural integrity (Fig 4F). For PS1-L, PS20-L, and PS30-L samples, there was an approximate 5-7% decline in stress levels after only 10 cycles, a change which then stabilized through to the 1000th cycle. This may be due to the brittle structure of the PS20-L and PS30-L samples. In PS1-L samples, the presence of non-crosslinked PVA chains during the cyclic test, potentially leads to structural loosening and a resulting decrease in residual stress. In contrast, this was not observed in PS samples with n-PTCS concentration greater than 1%.

[0222] Results from the tensile fatigue test show that PVA, PS1-L, PS20-L, and PS30-L samples experienced approximately 40% fatigue failure after 10 cycles, with a continuous reduction in their initial tension by about 44%, 45%, 47%, and 22%, respectively, by the 1000th cycle. In contrast, PS5-L and PS10-L samples showed only 15% failure after 10 cycles and retained approximately 70% and 83% of their initial tension by the 1000th cycle (Fig. 5A), highlighting their high elasticity and strong covalent bond structure. Notably, all samples, including PVA control and crosslinked samples, exhibited deformation after 1000 cycles. However, PS5-L and PS10-L samples demonstrated reversible deformation within a 10-minute timeframe, emphasizing their super flexible characteristics.With the uniaxial elasticity characterized in the tensile and fatigue tests, there were some indications that the samples were highly flexible. To further assess this flexibility, the implementation of a straightforward twisting test was designed. This test aimed to evaluate the flexibility properties of both pure PVA and composite samples under the application of shear stress through continuous twisting 360 °. As illustrated in Figs. 4G and 4H, the number of twisting cycles at the failure point demonstrated a significant increase with the crosslinking. Notably, the PS10-L samples demonstrated exceptional flexibility, reaching a maximum twisting number of 18 cycles. However, the rigid structure of the PVA films and the brittle structure of the PS20-L and PS30-L resulted in sample fractures occurring at lower cycle counts.

[0223] In conjunction with the previous test, the strength and elasticity of the samples were further assessed through suture retention tests. Suture retention is an important property, particularly in the context of membrane implants and their anastomotic strength, especially in vascular applications. To gauge the impact of crosslinking in PVA films and their improved mechanical properties on anastomotic features, suture retention tests were conducted to quantitatively measure the strength of suture retention.

[0224] The mean suture retention strength for the PVA control film was 9.8 ± 0.7 g. As depicted in Fig. 5B, all composite samples, except PS30-L, significantly surpassed this level. The PS10-L sample exhibited the maximum suture retention strength, measuring 26 ± 3.6 g, showcasing superior performance compared to other samples. Furthermore, camera-based monitoring (not shown, see reference

[0086] ) validated that the primary failure occurred in both PVA and PS30 samples due to their rigidity and brittleness, attributed to the presence of a hole defect introduced by a needle. The interpretation of principle strain distribution mapping (not shown, see reference

[0086] ) tends to confirm this hypothesis, highlighting areas of high strain with a red color, and areas of low strain with a blue color.

[0225] In heat maps of the PVA and PS5 samples, in particular, a high strain concentration was evident around the suture insertion point and the presence of dark blue strain mapping distal from the suture insertion point indicated insufficient suture retention by the bulk material. In contrast, the PS10, PS20, and PS30 samples demonstrated increased strain at the suture insertion point, however, this strain was more evenly distributed across the bulk material. This is indicated by the lack of blue coloring on the surface, and a decreased color change gradient.

[0226] In summary, the morphological and mechanical investigation of the PS samples indicates that addition of concentrations of 1% and 5% crosslinking agent n-PTCS may not be sufficient to crosslink the entire PVA chain, thereby failing to enhance the mechanical and stability properties of the control PVA film compared to samples containing 10% n-PTCS. Conversely, adding 20% and 30% of n-PTCS may result in undesirably high levels of crosslinking, significantly increasing the brittleness of the PVA membranes. Given that the PS10-L sample exhibits high elasticity, strength, flexibility, and suture retention, 10% was identified as the optimized concentration of crosslinking forthe crosslinking agent n-PTCS for effectively crosslinking the PVA membrane and providing desirable mechanical properties. The PS10-L crosslinked sample was subjected to further tests to explore its blood and bacterial repellency.Example 8: Blood and Plasma Repellency Studies

[0227] The blood and plasma repellency of control PVA and PS10-L samples was evaluated using plasma and whole blood clotting assays. Sample resistance to blood clot adhesion was assessed by measuring attached clot mass and examining clot adhesion with SEM analysis. PS10-L samples exhibited significantly lower amounts of clot mass (14.4 ± 4 mg) adhered to their surfaces compared to PVA films (120 ± 36 mg, P <0.0005). SEM analysis confirmed minimal adhesion of blood cells and no visible fibrin clot adhesion on the PS10-L samples, while dense clot layers were observed on the PVA samples (not shown, see reference

[0086] ). Plasma clotting assays further revealed the superior antithrombotic properties of PS10-L samples. PS10-L samples significantly increased plasma clotting times to 966 ± 204 s compared with PVA samples 459.6 ± 65 s (P < 0.0001) (Fig. 6B). In addition, SEM images revealed that the fibrin clot completely covered PVA samples, while no evident clot adhesion was observed on PS10-L samples (not shown, see reference

[0086] ). Consistent with the plasma clotting time, the blood clotting time revealed significant delays for PS10-L samples compared to pure PVA samples (P < 0.0005) (Fig. 6D). Coagulation started within 3.6 ± 0.5 min for PVA samples, whereas PS10-L samples showed a delay of at least two-fold, with clots starting to form after 9.6 ± 0.5 min. After 10 min, PVA samples were observed to be entirely covered by blood clots, whereas PS10-L samples exhibited minimal signs of blood clot adhesion on their surface (see reference

[0086] ). Blood and plasma sliding time analysis further emphasized the enhanced repellency properties of PS10-L surfaces, as evidenced by the immediate sliding of blood and plasma droplets on these surfaces, in contrast to PVA samples that showed no sliding properties( not shown, see reference

[0086] ).

[0228] To evaluate the red blood cell adhesion before clot formation and upon initial contact with the samples, a blood staining test was conducted. Samples were immersed in citrated human whole blood for 30 s, and adhered blood cells were then detached in water. The absorbance of the solution was measured using a plate reader at 450 nm 54. PS10-L films exhibited significantly fewer adhered blood cells compared to PVA samples, as indicated by a significantly lower absorbance of 0.17 ± 0.07 for PS10-L versus 1.03 ± 0.17 for PVA (Figure 6d-i and d-ii) (P < 0.0001) (Fig. 6C). This substantial reduction in blood cell adhesion aligns with the observations from SEM images of the blood clot adherence test, confirming the super repellency properties of PS10-L samples. These results align with findings from previous studies, which have shown the effectiveness of the lubricant layer in attenuating plasma and blood clotting and non-specific adhesion of proteins and cells [28, 38, 55, 56],Bacterial Adhesion and Repellancy

[0229] Before a biofilm can form and stabilize on a surface, bacterial substances must first find a surface to settle and adhere to 57. To assess the resistance of control PVA and PS10-L samples to bacterial adhesion, movement, and settlement, various bacterial adhesion tests were conducted. These tests included bacterial migration, adhesion, and stamping assays, utilizing Gramnegative GFP-tagged E. coli bacteria commonly found in clinical environments.

[0230] In the bacterial migration test (Figure 7A), noticeable adhesion, growth, and migration were observed on PVA samples. Additional details of the bacterial migration test are provided in reference

[0086] which is incorporated by reference herein for those details. In contrast, PS10-L samples acted as a barrier, preventing bacterial movement due to their non-adhesive and slippery nature. Following the test, adhered bacteria were detached from the samples, diluted, cultured on an agar plate, and plate coverage was measured. Plates cultured with bacteria from PS10-L samples exhibited a significantly lower coverage of bacterial colonies when compared to PVA samples (P< 0.0005) (Fig. 7A)

[0231] In the bacterial adhesion test, samples were immersed in a highly concentrated bacterial solution for 24 h and then rinsed to remove loosely attached bacteria. Detached bacteria were cultured, and CFU was measured to assess bacterial adhesion on lubricant-infused and control samples. Consistent with the migration test results, PS10-L samples exhibited a significantly lower mean bacterial colony count (5 x 103 CFU / mL) compared to PVA samples (9 x 105 CFU / mL, P<0.0005) (Fig. 7B). Before detachment, images of the samples showed a visible green bacterial layer on PVA samples (not shown, see reference

[0086] ), indicating strong adhesion even after gentle washing and without UV exposure. In contrast, PS10-L samples showed no distinct green layer, demonstrating their resistance to bacterial attachment.

[0232] To further evaluate the bacteria-repellent properties of the surfaces, a stamping assay was conducted to simulate conditions similar to high-touch surfaces in hospital settings (a schematic of this test is shown in reference

[0086] ). After the test, samples were rinsed and transferred to a fresh LB medium to detach adherent bacteria through agitation. The detached bacteria were then serially diluted 105 times, and CFUs were quantified by inoculating 20 pL of the diluted solution onto agar plates after 24 h. As seen in Fig. 7C, PS10-L samples stamped with GFP-tagged E. coli exhibited a 100-fold reduction in mean bacterial colony formation when compared to PVA samples (1 x 102 CFU / mL and 1 x 104 CFU / mL respectively). Moreover, the sliding behavior of concentrated bacterial droplets was investigated on control PVA and PS10-L samples (not shown, see reference

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Claims

We claim:1 . A method for making a silane-crosslinked poly(vinyl alcohol) (PVA) film comprising the steps of:(a) adding a selected amount of one or more silane crosslinking agent to an aqueous solution of PVA to generate an aqueous film-forming solution; and(b) forming a film of the silane-crosslinked PVA from the aqueous film-forming solution on a substrate and removing aqueous solvent from the solution to form the film, wherein the one or more silane-crosslinking agent is an organosilane of formula I:RiR2R3-Si-X,I where: each X is, independently, Cl, alkoxy, or acyloxy (-O-CO-R), where R is an optionally substituted alkyl group having 1 to 3 carbon atoms, an optionally substituted cycloalkyl having 6-12 carbon atoms or an optionally substituted phenyl group; each Ri is, independently, hydrogen, an optionally substituted alkyl group, an optionally substituted cycloalkyl group, an optionalluy substituted alkenyl group, an optionally substituted aryl group or a siloxane group of formula:-O-Si-(R4)3;R2is Ri or X;R3is Ri or X; and each R4is, independently, an optionally substituted alkyl group, a optionally substituted cycloalkyl group, an optionally substituted alkenyl group, an optionally substituted alkoxy group or an optionally substituted aryl group.

2. The method of claim 1 , wherein the amount of one or more silane crosslinking agent added to the aqueous solution of PVA ranges from 1% to 40% volume of agent / volume of polymer solution3. The method of claim 2, wherein the amount of one or more silane crosslinking agent added to the aqueous solution of PVA ranges from 5% to 20% v / v.

4. The method of claim 2, wherein the amount of one or more silane crosslinking agent added to the aqueous solution of PVA ranges from 5% to 15% v / v.

5. The method of any one of claims 1-4, wherein the amount of PVA dissolved in the aqueous solution ranges from 5% to 30% weight of PVA / volume of aqueous solvent6. The method of any one of claims 1-4, wherein the amount of PVA dissolved in the aqueous solution ranges from 10% to15% weight of PVA / volume of aqueous solvent.

7. The method of any one of claims 1-6, wherein the aqueous solvent is water.

8. The method of any one of claims 1 -6, wherein the aqueous solution of PVA is formed by addition of solid PVA to the aqueous solvent at a temperature of 20-80 °C with stirring to dissolve PVA.

9. The method of any one of claims 1-6, where the PVA ranges in Mw (weight average molecular weight) from 5,000 to 200,000 D and where the PVA is 70-100% hydrolyzed (contains from 0-30% residual acetate residues).

10. The method of any one of claims 1-6, where the PVA ranges in Mw from 89,000 to 98,000 D and where the PVA is 95% or more hydrolyzed.

11. The method of any one of claims 1-10, wherein the aqueous solution containing one or more silane crosslinking agents and PVA is heated to a temperature ranging from 50 to 70 °C for 1- 12 hours prior to film formation.

12. The method of any one of claims 1-11 , wherein the film generated ranges in thickness from 200-400 microns.

13. The method of any one of claims 1-12, wherein the substrate upon which the film is formed is ceramic, plastic, glass, quartz or metal.

14. The method of any one of claims 1-13, wherein the film formed is self-supporting.

15. A method for making a lubricant infused PVA film which comprises the steps:(a) making a silane-crosslinked poly(vinyl alcohol) (PVA) film as in any one of claims 1- 14; and(b) infusing the film with a selected amount of silicone oil for a time sufficient for absorption of lubricant into the silane-crosslinked poly(vinyl alcohol) (PVA) film; and(c) holding the lubricated film at a tilt angle of about 45° for a time sufficient to remove excess lubricant from the film.

16. The method of claim 15, wherein the silane-crosslinked poly(vinyl alcohol) (PVA) film is washed with water and dried prior to infusion of the silicone oil.

17. The method of claim 15 or 16, wherein the lubricant is silicone oil.

18. The method of claim 15 or 16, wherein the lubricant is silicone oil having viscosity ranging from 10-1000 cSt.

19. The method of claim 15 or 16, wherein the lubricant is silicone oil having viscosity of of 250-450 cSt.

20. The method of any one of claims 15-19, wherein the silicone oil is medical grade.

21. A silane-crosslinked poly(vinyl alcohol) (PVA) film crosslinked with a silane-crosslinking agent of formula I:RiR2R3-Si-X,I where: each X is independently Cl, alkoxy, or acyloxy (-O-CO-R), whereR is an optionally substituted alkyl group having 1 to 3 carbon atoms, an optionally substituted cycloalkyl havig 6-12 carbon atoms or an optionally substituted phenyl group; each Ri is independently, an optionally substituted alkyl group, an optionally substituted cycloalkyl group, an optionalluy substituted alkenyl group, an optionally substituted aryl group, hydrogen, or a siloxane group of formula:-O-Si-(R4)3;R2is Ri or X;R3is Ri or X; and each R4is independently an optionalluy substituted alkyl group, a optionally substituted cycloalkyl group, an optionally substituted alkenyl group, an optionally substituted alkoxy group or an optionally substituted aryl group.

22. A lubricated silane-crosslinked PVA film wherein a silane-crosslinked PVA film of claim 21 is lubricated with silicone oil.

23. A silane-crosslinked PVA film or lubricated-infused film made by the method of any one of claims 1-20.24 An article having at least one surface, at least a portion of which surface contacts a biological fluid, wherein the portion of the at least one surface which contacts the biological fluid is coated with a silane-crosslinked PVA film infused with silicone oil of claim 22 or 23.

25. The article of claim 24, wherein the biological fluid is blood, plasma, or a fluid containing one or more microorganism.

26. The method, crosslinked film, lubricated crosslinked film or article of any preceding claim wherein, in the silane crosslinking agent, X is Cl or alkoxy.

27. The method, crosslinked film, lubricated crosslinked film or article of any preceding claim, wherein, in the silane crosslinking agent, Ri is an alklyl, an alkoxyl or an aryl group.

28. The method, crosslinked film, lubricated crosslinked film or article of any preceding claim, wherein, in the silane crosslinking agent, Ri is an alkyl, an alkoxyl or an aryl group.

29. The method, crosslinked film, lubricated crosslinked film or article of any preceding claim, wherein, in the silane crosslinking agent, X is Cl.

30. The method, crosslinked film, lubricated crosslinked film or article of any preceding claim, wherein, in the silane crosslinking agent, R2and R3are both Cl.

31. The method, crosslinked film, lubricated crosslinked film or article of any preceding claim, wherein, in the silane crosslinking agent, R-i is an alkyl group having 1-6 carbon atoms.

32. The method, crosslinked film, lubricated crosslinked film or article of any preceding claim, wherein in the silane crosslinking agent Ri is an n-propyl group.

33. The method, crosslinked film, lubricated crosslinked film or article of any preceding claim, wherein the silane crosslinking agent is n-propyl trichlorosilane.

34. A method of preventing biofouling of an article surface or a device surface that contacts a biological fluid which comprises providing a lubricant-infused silane-crosslinked PVA film on the surface of the article or device that contacts the biological fluid, wherein the silane-crosslinked PVA film or lubricated film is a film of any one of claims 21-23 or 26-32 or wherein the silane-crosslinked PVA film is a film prepared by the method of any one of claims 1-14, or wherein the lubricant-infused silane-crosslinked PVA film is a film prepared by the method of any one of claims 15-20.

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