Immune-compatible semiconducting polymers for bioelectronics

Abstract

Implantable bioelectronic semiconducting polymers including thiophene and / or selenophene are provided. Films including the polymers coated on substrates are further provided. Organic electrochemical transistors including channels including the polymers are further provided. Methods of preparing the polymers are further provided. Bioelectronic implant comprising polymers coated on substrates are further provided.

Description

IMMUNE-COMPATIBLE SEMICONDUCTING POLYMERS FOR BIOELECTRONICS STATEMENT REGARDING FEDERALLY FUNDED RESEARCH

[0001] This invention was made with government support under EB034563 awarded by the National Institutes of Health, DMR2105367 awarded by the National Science Foundation, and N00014-21-1-2266 awarded by the Office of Naval Research. The government has certain rights in the invention. TECHNICAL FIELD

[0002] The present disclosure relates to polymers. BACKGROUND

[0003] Implantable bioelectronics have vital roles in healthcare and biological studies. Immune-mediated foreign-body response (“FBR”) currently challenges the achievement of long-term function and minimization of inflammatory reaction. FBR limits functional longevity of implants and causes side effects for patients. FBR triggers the cascade of immune cell recruitment, foreign body giant cell (“FBGC”) formation, collagen deposition, and encapsulation of the functional implants. For bioelectronic devices, FBR results in an increase of device-tissue interface impedance for transduction of electrical or chemical signals.

[0004] Because FBR behaviors for semiconducting polymers have not been characterized, the influences of different chemical designs and physical properties of semiconducting polymers on FBR behaviors remain elusive. For the molecular designs of semiconducting polymers, no design strategy for suppressing FBR has been reported.

[0005] Though semiconducting polymers have shown promise for direct electrical interfacing on bio-tissues, the understanding of the in vivo immune compatibility of such polymers is limited. Further, strategies for minimizing FBR through molecular design remain underexplored.

[0006] Thus, there is a need for molecular design strategies to enhance the immune compatibility of semiconducting polymers, such as by suppression of macrophage activation. Further, there is a need for polymer side-chain functionalization that decreases FBR by downregulating expression of inflammatory biomarkers. Further, there is a need for semiconductor polymers that suppress FBR while still providing high electrical performance.SUMMARY

[0007] In an example, the present disclosure provides an implantable bioelectronic semiconducting polymer including thiophene and / or selenophene. The polymer may include a thiophene backbone. The backbone may include selenophene. The polymer may include side chains including oligo(ethylene glycol) units. The polymer may include side chains including tri(ethylene glycol) units. The polymer may include side chains including a terminal. A charge-carrier mobility of the polymer is about 1 cm2·V-1·s-1.

[0008] In another example, the present disclosure provides a film including the polymer of examples of the present disclosure coated on a substrate.

[0009] In yet another example, the present disclosure provides an organic electrochemical transistor (“OECT”), including a channel including the polymer of examples of the present disclosure.

[0010] In yet another example, the present disclosure provides a method of preparing the polymer of examples of the present disclosure, including: heating a solution of an azido- substituted dibromo-bithiophene monomer of formula (II)and 2,5-bis(trialkylstannyl)thiophene or 2,5-bis(trialkylstannyl)selenophene, to provide an azido-substituted polymer of formula (III)wherein X is S or Se; depositing the polymer of formula (III) on a substrate to provide a coated substrate; and submerging the coated substrate in a precursor solution of an alkyne to provide the polymer. The alkyne may be selected from.

[0011] In yet another example, the present disclosure provides a bioelectronic implant including a polymer coated on a substrate.

[0012] Further areas of applicability will become apparent from the description provided herein. It should be understood that the description and specific examples are intended for purposes of illustration only and are not intended to limit the scope of the present disclosure. DRAWINGS

[0013] In order that the present disclosure may be well understood, there will now be described various forms thereof, given by way of example, reference being made to the accompanying drawings. The components in the figures are not necessarily to scale.

[0014] FIG. 1 illustrates an overlay of Fourier-Transform infrared (“FTIR”) spectra demonstrating side-chain functionalization of p(g2T-T)-a and p(g2T-Se)-a to THP- and TMO- substituted semiconducting polymers;

[0015] FIG. 2 illustrates plots of depth-profiling XPS spectra demonstrating S 2p and N 1s peaks for p(g2T-T)-a (top) and p(g2T-T)-TMO (bottom);

[0016] FIG.3 illustrates XPS characterization showing N 1s and S 2p peaks on top and bottom surfaces of a film of an example of a polymer before and after side-chain functionalization;

[0017] FIG. 4 illustrates a bar graph plot of the results of an MTT assay of the examples of semiconducting polymers, with uncoated SEBS substrates used as a control, with values representing mean values ± standard error of the mean (“SEM”);

[0018] FIG. 5 illustrates live / dead cell imaging of RAW 264.7 cells incubated with SEBS substrates coated with examples of semiconducting polymers, with scale bars of 200 μm;

[0019] FIG. 6 illustrates a bar graph plot of collagen density calculation for examples of semiconducting polymers coated on SEBS substrates and implanted in mice for 1 week, with values representing mean values ± SEM;

[0020] FIG.7 illustrates Masson’s trichome-stained tissue sections after 4-week subcutaneous implantation with SEBS substrates coated with each of p(g2T-T), p(g2T-Se), p(g2T-Se)-THP, and p(g2T-Se)-TMO semiconducting polymers, with scale bars of 1 millimeter;

[0021] FIG.8 illustrates a bar graph plot of quantification of collagen deposition density at the polymer-tissue interface after 4-week subcutaneous implantation with SEBS substrates coated with each of p(g2T-T), p(g2T-Se), p(g2T-T)-THP, p(g2T-Se)-THP, p(g2T-T)-TMO, and p(g2T-Se)-TMO, with values representing mean values ± SEM;

[0022] FIG. 9 illustrates a bar graph plot of CD68 immune-cell population at the polymer- tissue interface after 4-week subcutaneous implantation with SEBS substrates coated with each of p(g2T-T), p(g2T-Se), p(g2T-T)-THP, p(g2T-Se)-THP, p(g2T-T)-TMO, and p(g2T-Se)- TMO, with values representing mean values ± SEM;

[0023] FIG. 10 -cell population at the polymer- tissue interface after 4-week subcutaneous implantation with SEBS substrates coated with each of p(g2T-T), p(g2T-Se), p(g2T-T)-THP, p(g2T-Se)-THP, p(g2T-T)-TMO, and p(g2T-Se)- TMO, with values representing mean values ± SEM;

[0024] FIG. 11 illustrates a plot of the quantification of collagen density as a function of the distance from the implant surface to the tissue surface after implantation with SEBS substrates coated with each of p(g2T-T), p(g2T-Se), p(g2T-T)-THP, p(g2T-Se)-THP, p(g2T-T)-TMO, and p(g2T-Se)-TMO, with values representing mean values ± SEM;

[0025] FIG. 12 illustrates a bar graph plot of the relative area under the curve (“AUC”) for each of the plots illustrated in FIG. 11;

[0026] FIG. 13 illustrates a bar graph plot of the relative collagen Type I mRNA expression levels (such as fold changes) in the implanted region for each of p(g2T-T), p(g2T-Se), p(g2T- Se)-THP, and p(g2T-Se)-TMO, with values representing mean values ± SEM;

[0027] FIG. 14 illustrates a bar graph plot of the relative collagen Type III mRNA expression levels (such as fold changes) in the implanted region for each of p(g2T-T), p(g2T-Se), p(g2T- Se)-THP, and p(g2T-Se)-TMO, with values representing mean values ± SEM;

[0028] FIG. 15 illustrates a bar graph plot of the relative collagen Type I mRNA expression levels (such as fold changes) in the implanted region for each of p(g2T-T), p(g2T-Se), p(g2T- T)-THP, p(g2T-Se)-THP, p(g2T-T)-TMO, and p(g2T-Se)-TMO, with values representing mean values ± SEM;

[0029] FIG. 16 illustrates a bar graph plot of the relative collagen Type III mRNA expression levels (such as fold changes) in the implanted region for each of p(g2T-T), p(g2T-Se), p(g2T- T)-THP, p(g2T-Se)-THP, p(g2T-T)-TMO, and p(g2T-Se)-TMO, with values representing mean values ± SEM;

[0030] FIG. 17 illustrates a bar graph plot of the quantification of CD68 immune-cell population at the tissue-polymer interface from immunofluorescence images for each of p(g2T- T), p(g2T-Se), p(g2T-Se)-THP, and p(g2T-Se)-TMO, with values representing mean values ± SEM;

[0031] FIG. 18 -cell population at the tissue-polymer interface from immunofluorescence images for each of p(g2T- T), p(g2T-Se), p(g2T-Se)-THP, and p(g2T-Se)-TMO, with values representing mean values ± SEM;

[0032] FIG. 19 illustrates a bar graph plot of expression level of pro-inflammatory marker CCR7 in cells exposed in vitro to each of p(g2T-T), p(g2T-Se), p(g2T-Se)-THP, and p(g2T- Se)-TMO, with values representing mean values ± SEM;

[0033] FIG.20 illustrates a bar graph plot of expression level of pro-inflammatory marker IFN- in cells exposed in vitro to each of p(g2T-T), p(g2T-Se), p(g2T-Se)-THP, and p(g2T-Se)- TMO, with values representing mean values ± SEM;

[0034] FIG.21 illustrates a bar graph plot of expression level of pro-inflammatory marker GM- CSF in cells exposed in vitro to each of p(g2T-T), p(g2T-Se), p(g2T-Se)-THP, and p(g2T-Se)- TMO, with values representing mean values ± SEM;

[0035] FIG. 22 illustrates a bar graph plot of expression level of pro-inflammatory marker MCP-1 in cells exposed in vitro to each of p(g2T-T), p(g2T-Se), p(g2T-Se)-THP, and p(g2T- Se)-TMO, with values representing mean values ± SEM;

[0036] FIG. 23 illustrates a bar graph plot of expression level of pro-inflammatory marker IL- 23 in cells exposed in vitro to each of p(g2T-T), p(g2T-Se), p(g2T-Se)-THP, and p(g2T-Se)- TMO, with values representing mean values ± SEM;

[0037] FIG. 24 illustrates a bar graph plot of expression level of pro-inflammatory marker IL- 6 in cells exposed in vitro to each of p(g2T-T), p(g2T-Se), p(g2T-Se)-THP, and p(g2T-Se)- TMO, with values representing mean values ± SEM;

[0038] FIG. 25 illustrates a bar graph plot of expression level of pro-inflammatory marker IL- in vitro to each of p(g2T-T), p(g2T-Se), p(g2T-Se)-THP, and p(g2T-Se)- TMO, with values representing mean values ± SEM;

[0039] FIG. 26 illustrates a bar graph plot of expression level of pro-inflammatory marker IL- 27 in cells exposed in vitro to each of p(g2T-T), p(g2T-Se), p(g2T-Se)-THP, and p(g2T-Se)- TMO, with values representing mean values ± SEM;

[0040] FIG. 27 illustrates a bar graph plot of expression level of pro-inflammatory marker IL- 12p70 in cells exposed in vitro to each of p(g2T-T), p(g2T-Se), p(g2T-Se)-THP, and p(g2T- Se)-TMO, with values representing mean values ± SEM;

[0041] FIG. 28 illustrates a bar graph plot of expression level of pro-inflammatory marker IL- in vitro to each of p(g2T-T), p(g2T-Se), p(g2T-Se)-THP, and p(g2T-Se)- TMO, with values representing mean values ± SEM;

[0042] FIG.29 illustrates a bar graph plot of expression level of anti-inflammatory marker IL- 10 in cells exposed in vitro to each of p(g2T-T), p(g2T-Se), p(g2T-Se)-THP, and p(g2T-Se)- TMO, with values representing mean values ± SEM;

[0043] FIG.30 illustrates a bar graph plot of expression level of anti-inflammatory marker IL- 4 in cells exposed in vitro to each of p(g2T-T), p(g2T-Se), p(g2T-Se)-THP, and p(g2T-Se)- TMO, with values representing mean values ± SEM;

[0044] FIG. 31 illustrates a bar graph plot of cell toxicity of p(g2T-Se) at various concentrations during in vitro cell treatment with or without lipopolysaccharide (“LPS”), with values representing mean values ± SEM;

[0045] FIG.32 illustrates a bar graph plot of cell toxicity of p(g2T-T) at various concentrations during in vitro cell treatment with or without LPS, with values representing mean values ± SEM;

[0046] FIG. 33 illustrates a bar graph plot of cell toxicity of selenophene at various concentrations during in vitro cell treatment with or without LPS, with values representing mean values ± SEM;

[0047] FIG.34 illustrates a bar graph plot of cell toxicity of thiophene at various concentrations during in vitro cell treatment with or without LPS, with values representing mean values ± SEM;

[0048] FIG. 35 illustrates a bar graph plot of mean fluorescence intensity (“MFI”) of inflammation-related biomarker p-p38 treated with selenophene at various concentrations and with or without LPS, with values representing mean values ± SEM;

[0049] FIG. 36 illustrates a bar graph plot of MFI of inflammation-related biomarker p-ERK treated with selenophene at various concentrations and with or without LPS, with values representing mean values ± SEM;

[0050] FIG. 37 illustrates a bar graph plot of MFI of inflammation-related biomarker iNOS treated with selenophene at various concentrations and with or without LPS, with values representing mean values ± SEM;

[0051] FIG. 38 illustrates a bar graph plot of MFI of inflammation-related biomarker p-JNK treated with selenophene at various concentrations and with or without LPS, with values representing mean values ± SEM;

[0052] FIG. 39 illustrates a bar graph plot of MFI of inflammation-related biomarker p-p38 treated with thiophene at various concentrations and with or without LPS, with values representing mean values ± SEM;

[0053] FIG. 40 illustrates a bar graph plot of MFI of inflammation-related biomarker p-ERK treated with thiophene at various concentrations and with or without LPS, with values representing mean values ± SEM;

[0054] FIG. 41 illustrates a bar graph plot of MFI of inflammation-related biomarker iNOS treated with thiophene at various concentrations and with or without LPS, with values representing mean values ± SEM;

[0055] FIG. 42 illustrates a bar graph plot of MFI of inflammation-related biomarker p-JNK treated with thiophene at various concentrations and with or without LPS, with values representing mean values ± SEM;

[0056] FIG. 43 illustrates a bar graph plot of MFI of inflammation-related biomarker p-p38 treated with p(g2T-Se) at various concentrations and with or without LPS, with values representing mean values ± SEM;

[0057] FIG. 44 illustrates a bar graph plot of MFI of inflammation-related biomarker p-ERK treated with p(g2T-Se) at various concentrations and with or without LPS, with values representing mean values ± SEM;

[0058] FIG. 45 illustrates a bar graph plot of MFI of inflammation-related biomarker iNOS treated with p(g2T-Se) at various concentrations and with or without LPS, with values representing mean values ± SEM;

[0059] FIG. 46 illustrates a bar graph plot of MFI of inflammation-related biomarker p-JNK treated with p(g2T-Se) at various concentrations and with or without LPS, with values representing mean values ± SEM;

[0060] FIG. 47 illustrates a bar graph plot of MFI of inflammation-related biomarker p-p38 treated with p(g2T-T) at various concentrations and with or without LPS, with values representing mean values ± SEM;

[0061] FIG. 48 illustrates a bar graph plot of MFI of inflammation-related biomarker p-ERK treated with p(g2T-T) at various concentrations and with or without LPS, with values representing mean values ± SEM;

[0062] FIG. 49 illustrates a bar graph plot of MFI of inflammation-related biomarker iNOS treated with p(g2T-T) at various concentrations and with or without LPS, with values representing mean values ± SEM;

[0063] FIG. 50 illustrates a bar graph plot of MFI of inflammation-related biomarker p-JNK treated with p(g2T-T) at various concentrations and with or without LPS, with values representing mean values ± SEM;

[0064] FIG. 51 illustrates a schematic of an example of an organic electrochemical transistor (“OECT”) device;

[0065] FIG.52 illustrates a plot of transfer characteristics including transconductance (gm) and drain current for each of p(g2T-T), p(g2T-Se), p(g2T-Se)-THP, and p(g2T-Se)-TMO as OECT channels;

[0066] FIG. 53 illustrates a bar graph plot of mobility and normalized transconductance for each of p(g2T-T), p(g2T-Se), p(g2T-Se)-THP, and p(g2T-Se)-TMO, with values representing mean values ± SEM;

[0067] FIG. 54 illustrates a bar graph plot of mobility and normalized transconductance for each of p(g2T-T)-a and p(g2T-Se)-a, with values representing mean values ± SEM;

[0068] FIG. 55 illustrates a bar graph plot of mobility and normalized transconductance for each of p(g2T-T)-THP, p(g2T-T)-TMO, p(g2T-Se)-THP, and p(g2T-T)-TMO, with values representing mean values ± SEM;

[0069] FIG. 56 illustrates a bar graph plot of relative degree of crystallinity and lamellar spacing for each of p(g2T-T), p(g2T-Se), p(g2T-Se)-THP, and p(g2T-Se)-TMO; and

[0070] FIG.57 illustrates a bar graph plot of normalized UV-Vis absorption spectra of p(g2T- T), p(g2T-Se), p(g2T-Se)-THP, and p(g2T-Se)-TMO.

[0071] The drawings described herein are for illustration purposes only and are not intended to limit the scope of the present disclosure in any way. DETAILED DESCRIPTION

[0072] The following description is merely exemplary in nature and is not intended to limit the present disclosure, application, or uses.

[0073] In describing elements of the present disclosure, the terms “1st,” “2nd,” “first,” “second,” “A,” “B,” “(a),” “(b),” and the like may be used herein. These terms are only used to distinguish one element from another element, but do not limit the corresponding elements irrespective of the nature or order of the corresponding elements.

[0074] Numerical values, including endpoints of ranges, may be expressed herein as approximations preceded by the term “about,” “approximately,” or the like. In such cases, other examples include the particular numerical values. Regardless of whether a numerical value is expressed as an approximation, two examples are included in this disclosure: one expressed as an approximation, and another not expressed as an approximation. It will be further understood that an endpoint of each range is significant both in relation to another endpoint, and independently of another endpoint.

[0075] The uses of the terms “a” and “an” and “the” and similar referents in the context of describing the present disclosure (especially in the context of following claims) are to be construed to cover both the singular and the plural, unless otherwise indicated herein or clearly contradicted by context. Recitation of ranges of values herein are merely intended ot serve as a shorthand method of referring individually to each separate value falling within the range, unless otherwise indicated herein, and each separate value is incorporated into the specification as if it were individually recited herein. All methods described herein may be performed in any suitable order unless otherwise indicated herein or otherwise clearly contradicted by context.

[0076] As used herein, the terms “comprise(s),” “include(s),” “having,” “has,” “can,” “contain(s),” and variants thereof, are intended to be open-ended transitional phrases, terms, or words that do not preclude the possibility of additional acts, structures, elements, or components. The present description also contemplates other embodiments “comprising,” “consisting of,” and “consisting essentially of” the examples or elements presented herein, whether explicitly set forth or not.

[0077] As used herein, the term “about,” when used in the context of a numerical value or range set forth means a variation of ±15%, or less, of the numerical value. For example, a value differing by ±15%, ±14%, ±10%, or ±5%, among others, would satisfy the definition of “about,” unless more narrowly defined in particular instances.

[0078] Herein is described design strategies for incorporating immunomodulatory moieties into both the backbones and side chains of semiconducting polymers, thereby substantially suppressing FBR as indicated by up to about a 68% decrease in collagen density. By systematic and rigorous immunological assays, including PCR-based collagen quantification and cytokine assays, combined with an in vitro mechanistic study of anti-inflammatory effect, a reasonably complete understanding of the mechanism of the suppression effect on the FBR was obtained. By measuring in organic electrochemical transistor (“OECT”) devices, the suppression of FBRresulted in little detriment to the electrical performance of the semiconducting polymers, with charge-carrier mobility maintaining about 1 cm2·V-1·s-1.

[0079] In an example, the present disclosure provides a semiconducting polymer film including a substrate on which a semiconducting polymer is coated.

[0080] In an example, a semiconducting polymer may include thiophene and / or selenophene.

[0081] In certain examples, the polymer may include a thiophene backbone. In certain examples, the backbone may include selenophene. In certain examples, the polymer may include side chains including oligo(ethylene glycol) units.oligo(ethylene glycol) units

[0082] In certain examples, the polymer may include side chains including tri(ethylene glycol) units or tetra(ethylene glycol) units.

[0083] In certain examples, the polymer has a charge-carrier mobility of from about 0.50 cm2·V-1·s-1to about 1.50 cm2·V-1·s-1, including, for example, from about, or to about, 0.51 cm2·V-1·s-1, or 0.52 cm2·V-1·s-1, or 0.53 cm2·V-1·s-1, or 0.54 cm2·V-1·s-1, or 0.55 cm2·V-1·s-1, or 0.56 cm2·V-1·s-1, or 0.57 cm2·V-1·s-1, or 0.58 cm2·V-1·s-1, or 0.59 cm2·V-1·s-1, or 0.60 cm2·V-1·s-1, or 0.61 cm2·V-1·s-1, or 0.62 cm2·V-1·s-1, or 0.63 cm2·V-1·s-1, or 0.64 cm2·V-1·s-1, or 0.65 cm2·V-1·s-1, or 0.66 cm2·V-1·s-1, or 0.67 cm2·V-1·s-1, or 0.68 cm2·V-1·s-1, or 0.69 cm2·V-1·s-1, or 0.70 cm2·V-1·s-1, or 0.71 cm2·V-1·s-1, or 0.72 cm2·V-1·s-1, or 0.73 cm2·V-1·s-1, or 0.74 cm2·V-1·s-1, or 0.75 cm2·V-1·s-1, or 0.76 cm2·V-1·s-1, or 0.77 cm2·V-1·s-1, or 0.78 cm2·V-1·s-1, or 0.79 cm2·V-1·s-1, or 0.80 cm2·V-1·s-1, or 0.81 cm2·V-1·s-1, or 0.82 cm2·V-1·s-1, or 0.83 cm2·V-1·s-1, or 0.84 cm2·V-1·s-1, or 0.85 cm2·V-1·s-1, or 0.86 cm2·V-1·s-1, or 0.87 cm2·V-1·s-1, or 0.88 cm2·V-1·s-1, or 0.89 cm2·V-1·s-1, or 0.90 cm2·V-1·s-1, or 0.91 cm2·V-1·s-1, or 0.92 cm2·V-1·s-1, or 0.93 cm2·V-1·s-1, or 0.94 cm2·V-1·s-1, or 0.95 cm2·V-1·s-1, or 0.96 cm2·V-1·s-1, or 0.97 cm2·V-1·s-1, or 0.98 cm2·V-1·s-1, or 0.99 cm2·V-1·s-1, or 1.00 cm2·V-1·s-1, or 1.01 cm2·V-1·s-1, or 1.02 cm2·V-1·s-1, or 1.03 cm2·V-1·s-1, or 1.04 cm2·V-1·s-1, or 1.05 cm2·V-1·s-1, or 1.06 cm2·V-1·s-1, or 1.07 cm2·V-1·s-1, or 1.08 cm2·V-1·s-1, 1.09 cm2·V-1·s-1, or 1.10 cm2·V-1·s-1, or 1.11 cm2·V-1·s-1, or 1.12 cm2·V-1·s-1, or 1.13 cm2·V-1·s-1, or 1.14 cm2·V-1·s-1, or 1.15 cm2·V-1·s-1, or 1.16 cm2·V-1·s-1, or 1.17 cm2·V-1·s-1, or 1.18 cm2·V-1·s-1, or 1.19 cm2·V-1·s-1, or 1.20 cm2·V-1·s-1, or 1.21 cm2·V-1·s-1, or 1.22 cm2·V-1·s-1, or 1.23 cm2·V-1·s-1, or 1.24 cm2·V-1·s-1, or 1.25 cm2·V-1·s-1, or 1.26 cm2·V-1·s-1, or 1.27 cm2·V-1·s-1, or 1.28 cm2·V-1·s-1, or 1.29 cm2·V-1·s-1, or 1.30 cm2·V-1·s-1, or 1.31 cm2·V-1·s-1, or 1.32 cm2·V-1·s-1, or 1.33 cm2·V-1·s-1, or 1.34 cm2·V-1·s-1, or 1.35 cm2·V-1·s-1, or 1.36 cm2·V-1·s-1, or1.37 cm2·V-1·s-1, or 1.38 cm2·V-1·s-1, or 1.39 cm2·V-1·s-1, or 1.40 cm2·V-1·s-1, or 1.41 cm2·V-1·s-1, or 1.42 cm2·V-1·s-1, or 1.43 cm2·V-1·s-1, or 1.44 cm2·V-1·s-1, or 1.45 cm2·V-1·s-1, or 1.46 cm2·V-1·s-1, or 1.47 cm2·V-1·s-1, or 1.48 cm2·V-1·s-1, or 1.49 cm2·V-1·s-1; or a range formed from any two of the foregoing charge-carrier mobilities, including any subranges therebetween.

[0084] In an example, the present disclosure provides a semiconducting polymer of formula (I):wherein X is an atom of an element selected from S and Se; and R is selected from4-((1-methyl-1H-1,2,3-triazol-4-yl)methyl)thiomorpholinyl-1,1-dioxide ("TMO").

[0085] In an example, a film may include the polymer of examples of the present disclosure coated on a substrate.

[0086] In an example, an organic electrochemical transistor (“OECT”) may include a channel including the polymer of examples of the present disclosure.

[0087] In an example, a method of preparing the polymer of examples of the present disclosure includes: heating a solution of an azido-substituted dibromo-bithiophene monomer of formula (II)and 2,5-bis(trialkylstannyl)thiophene or 2,5-bis(trialkylstannyl)selenophene, to provide an azido-substituted polymer of formula (III)wherein X is S or Se; depositing the polymer of formula (III) on a substrate to provide a coated substrate; and submerging the coated substrate in a precursor solution of an alkyne to providethe polymer. In certain examples, the alkyne is selected from.

[0088] In an example, a bioelectronic implant may include the polymer of examples of the present disclosure.

[0089] The compositions and processes described above may be better understood in connection with the following Examples. In addition, the following non-limiting examples are an illustration. The illustrated methods are applicable to other examples of semiconducting polymers of the present disclosure. The procedures described as general methods describe what is believed will be typically effective to prepare the compositions indicated. However, the person skilled in the art will appreciate that it may be necessary to vary the procedures for any given example of the present disclosure, for example, vary the order or steps and / or the chemical reagents used. EXAMPLES

[0090] I. Materials and Methods.

[0091] A. Materials

[0092] The chemicals used herein, including tetra(ethylene glycol), copper(I) iodide, copper(I) bromide, potassium tert-butoxide, iodine, triphenylphosphine, imidazole, N- bromosuccinimide, sodium azide, selenophene, n-butyllithium, trimethyltin chloride, N,N,N,N,N-pentamethyldiethylenetriamine, 2,5-bis(trimethylstannyl)thiophene, trimethyl(phenyl)tin, bromobenzene, anhydrous dichloromethane (“DCM”), anhydrous chloroform, anhydrous dimethylformamide (“DMF”), and anhydrous chlorobenzene were purchased from Sigma-Aldrich and used without further purification. 3,3’-Dibromo-2,2’- bithiophene was purchased from Chemscene. 4-Propargylthiomorpholine 1,1-dioxide was purchased from TCI. Tetrahydro-2-(2-propynyloxy)-2H-pyran was purchased from Oakwood Chemical. 5,5’-Dibromo-3,3’-bis(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)-2,2’-bithiophene was purchased from SunaTech Inc. Polystyrene-block-poly(ethylene-ran-butylene)-block- polystyrene (“SEBS”) was obtained from Asahi Kasei.

[0093] Male C57BL / mice (6-8 weeks) were purchased from Charles River Laboratory. RAW 264.7 cell line was obtained from ATCC and was cultured according to instructions. RAW 264.7 cell line was routinely checked for mycoplasma contamination.

[0094] B. Characterizations

[0095] Microwave polymerization was conducted using a Biotage Initiator +. Nuclear magnetic resonance (“NMR”) spectra were recorded on a Bruker Avance III HD console spectrometer (1H 400 MHz,13C 100 MHz) at 293 K. Chemical shifts were given in parts per million (“ppm”) with respect to tetramethylsilane (“TMS”) as an internal standard, and coupling constants (J) given in Hertz (“Hz”). High-resolution mass spectra (“HR-MS”) were recorded on an Agilent 6530 LC Q-TOF mass spectrometer using electrospray ionization with fragmentation voltage set at 70 V, and processed with an Agilent MassHunter Operating System. Number average molecular weight (Mn), weight average molecular weight (Mw), and polydispersity index (“PDI”) were evaluated by Tosoh EcoSEC size exclusion chromatography system (“GPC”) using DMF + 0.01 M LiBr as eluent (50°C) calibrated with polystyrene standards. The UV-Vis absorption spectra were recorded on the Shimadzu UV-3600 plus UV- VIS-NIR spectrophotometer. The atomic force microscope (“AFM”) imaging was done with the Bruker Multimode 8 AFM. The depth-profiling X-ray photoelectron spectroscopy (“XPS”) -ray source and a delay line detector (“DLD”) system with Ar1000+ with 5 keV to etch. Grazing-incidence X-ray diffraction (“GIXD”) was performed at the Advanced Photon Source at Argonne National Laboratory on beamline 8-ID-E, with photon energy 10.92 keV and collimated beam 200 μm x 10 μm (H x V) incident on the sample at an incident angle of 0.13°. GIXD samples were prepared by transferring thin films from OTS-treated substrates to Si wafer pieces. Samples were maintained in a rough vacuum environment (10-3mbar) during measurements, 217 mm away from a pixel array detector (Pilatus 1M, Dectris). Pairs of exposures of 5 seconds each with different detector heights were captured and combined to fill in gaps between the detector modules, demonstrating that the scattering pattern did not change during the measurement. The Matlab package GIXSGUI was used to apply all necessary corrections and combine the images, as well as to compute integrations (linecuts). The relative degree of crystallinity (“rDoC”) for each sample was computed from the sine-weighted integration of the partial pole figure for the (100) lamellar feature in each pattern and normalized by the sample thickness. The lamellar spacing was calculated for the out-of-plane (100) peak. The 2D images are displayed on the same (logarithmic) false color intensity scale.

[0096] II. Synthesis of 3,3’-bis(2-(2-(2-(2-azidoethoxy)ethoxy)ethoxy)ethoxy)-5,5’-dibromo- 2,2’-bithiophene Monomer (Compound 4).

[0097] 3,3’-bis(2-(2-(2-(2-azidoethoxy)ethoxy)ethoxy)ethoxy)-5,5’-dibromo-2,2’- bithiophene (Compound 4) was prepared according to Scheme 1.Scheme 1

[0098] A. Synthesis of 2,2’-((((((([2,2’-bithiophene]-3,3’diylbis(oxy))bis(ethane-2,1- diyl))bis(oxy))bis(ethane-2,1-diyl))bis(oxy))bis(ethane-2,1-diyl))bis9oxy))bis(ethan-1-ol) (Compound 1, Scheme 1)

[0099] To a nitrogen-gas-filled round-bottom flask (“RBF”) with a stirring bar, potassium tert- butoxide (37.3 mmol, 4.2 g), copper(I) iodide (5 mmol, 0.95 g), 3,3’-dibromo-2,2’-bithiophene (12.4 mmol, 4 g), and tetra(ethylene glycol) (12.4 mmol, 24 g) were added. The mixture was heated to 100°C for 20 hours. The mixture was cooled to room temperature and filtered. The solid was washed with DCM and the organic phase was washed with 1 M HCl and brine successively. The solvent was removed using rotary evaporation and the residue was purified by column chromatography (silica gel, EA). The final Compound 1 was isolated as a yellow oil (5 g, 73 %).1H NMR (400 MHz, CDCl3) J = 5.5 Hz, 2H), 6.85 (d, J = 5.5 Hz, 2H), 4.25 (t, J = 4.8 Hz, 4H), 3.90 (t, J = 4.8 Hz, 4H), 3.79 – 3.72 (m, 4H), 3.72 – 3.62 (m,16H), 3.62 – 3.55 (m, 4H), 2.46 (s, 2H);13C NMR (101 MHz, CDCl3115.00, 114.72, 72.47, 71.40, 70.93, 70.67, 70.38, 70.06, 61.76. HRMS (ESI) calcd for C24H39O10S2[M+H]+551.1979, found 551.1989.

[0100] B. Synthesis of 3,3’-bis(2-(2-(2-(2-iodoethoxy)ethoxy)ethoxy)ethoxy)-2,2’- bithiophene (Compound 2, Scheme 1)

[0101] To a nitrogen-gas-filled RBF with I2(14.2 mmol, 3.6 g), imidazole (16.4 mmol, 1.1 g), and Compound 1 (5.4 mmol, 3 g) in 40 mL DCM, PPh3(13.1 mmol, 3.4 g) in DCM was added at 0°C. The mixture was stirred at room temperature for 12 – 16 hours. The organic phase was washed with brine. The solvent was removed using rotary evaporation and the residue was purified by column chromatography (silica gel, ethyl acetate:hexanes = 1:1). The final Compound 2 was isolated as a yellow oil (2.4 g, 65 %).1H NMR (400 MHz, CDCl3(d, J = 5.6 Hz, 2H), 6.85 (d, J = 5.6 Hz, 2H), 4.29 – 4.19 (m, 4H), 3.96 – 3.86 (m, 4H), 3.74 (dt, J = 9.5, 5.8 Hz, 8H), 3.71 – 3.60 (m, 12H), 3.30 – 3.18 (m, 4H).13C NMR (101 MHz, CDCl3HRMS (ESI) calcd for C24H37I2O8S2[M+H]+771.0014, found 771.0022.

[0102] C. Synthesis of 5,5’-dibromo-3,3’-bis(2-(2-(2-(2-iodoethoxy)ethoxy)ethoxy)ethoxy)- 2,2’-bithiophene (Compound 3, Scheme 1)

[0103] To a nitrogen-gas-filled RBF, Compound 2 (2.2 mmol, 1.5 g) was dissolved in 30 mL THF and cooled to -10°C. N-bromosuccinimide (“NBS”) (4.6 mmol, 0.81 g) in 10 mL THF was added to the solution dropwise. The mixture was stirred at room temperature for 2 hours. The mixture was then quenched with aqueous sodium sulfite solution. The mixture was washed with brine and extracted with DCM. The solvent was removed using rotary evaporation and the residue was purified by column chromatography (silica gel, ethyl acetate:hexanes = 1:1). The final Compound 3 was isolated as a yellow oil (1.8 g, 98 %).1H NMR (400 MHz, CDCl3) – 4.13 (m, 4H), 3.93 – 3.83 (m, 4H), 3.72 (ddd, J = 15.0, 13.3, 8.4 Hz, 20H), 3.25 (t, J = 6.9 Hz, 4H);13C NMR (101 MHz, CDCl372.00, 71.72, 70.97, 70.80, 70.72, 70.27, 69.92. HRMS (ESI) calcd for C24H35Br2I2O8S2[M+H]+926.8224, found 926.8225.

[0104] D. Synthesis of 3,3’-bis(2-(2-(2-(2-azidoethoxy)ethoxy)ethoxy)ethoxy)-5,5’-dibromo- 2,2’-bithiophene (Compound 4, Scheme 1)

[0105] To a nitrogen-gas-filled RBF, Compound 3 (1.2 mmol, 1 g) was dissolved in 30 mL N- dimethylformamide (“DMF”) was added to the solution dropwise. The mixture was stirred at 60°C for 12 – 16 hours. The solvent was removed using rotary evaporation and the residuewas purified by column chromatography (silica gel, ethyl acetate:hexanes = 1:1). The final Compound 4 was isolated as a yellow oil (0.76 g, 84 %).1H NMR (400 MHz, CDCl36.85 (s, 2H), 4.20 (t, J = 4.7 Hz, 4H), 3.87 (t, J = 4.7 Hz, 4H), 3.78 – 3.61 (m, 20H), 3.38 (t, J = 4.9 Hz, 4H);13C NMR (101 MHz, CDCl370.73, 70.04, 69.89, 50.70. HRMS (ESI) calcd for C24H35Br2N6O8S2[M+H]+757.0319, found 757.0302.

[0106] III. Synthesis of 2,5-bis(trimethylstannyl)selenophene (Scheme 2).

[0107] 2,5-Bis(trimethylstannyl)selenophene (Compound 5) was prepared according to Scheme 2 below.selenophene 5Scheme 2

[0108] To a nitrogen-gas-filled RBF with selenophene (10 mmol, 1.3 g) in THF, n-butyllithium (21.8 mmol, 12.8 mL) was added dropwise at -78°C. The reaction was stirred at room temperature for 30 minutes. The mixture was cooled to -78°C. Trimethyltin chloride (25 mmol, 25 mL) was then added dropwise. The mixture was warmed to room temperature and stirred for 12 – 16 hours. The mixture was then poured into water and extracted with diethyl ether. The organic phase was then concentrated. The final Compound 5 was recrystallized from methanol as a white solid (1.5 g, 33 %).1H NMR (400 MHz, CDCl3– 0.27 (m, 18H).13C NMR (101 MHz, CDCl3-7.78.

[0109] IV. Polymer Synthesis from Compound 4 (Scheme 3).Scheme 3

[0110] To a mixture of Compound 4 (50 mg, 0.0774 mmol, 1.0 eq.), 2,5- bis(trimethylstannyl)thiophene (31.9 mg, 0.0774 mmol, 1.0 eq.) or 2,5- bis(trimethylstannyl)selenophene (Compound 5, 35.6 mg, 0.0774 mmol, 1.0 eq.), Pd(PPh3)4(3.6 mg, 0.0031 mmol, 0.04 eq.), and CuI (0.6 mg, 0.0031, 0.04 eq.) was added 2 mL of anhydrous DMF in a nitrogen-filled glovebox. The reaction vial was sealed and submitted to a microwave reactor with the following temperature profile: 2 minutes at 80°C, and 6 minutes at 100°C. After the reaction was cooled down, 10 mol% of trimethyl(phenyl)stannane were added and the crude polymer solution was heated again for 2 minutes at 80°C. To complete the end-capping of the polymer, 10 mol% of bromobenzene was added, and the reaction vessel submitted to microwave heating for 2 minutes at 80°C. The crude polymer was then precipitated into methanol, filtered, loaded to a Soxhlet thimble, and washed successively with hexanes and ethyl acetate (each for 24 hours). The polymer was finally collected from the thimble with chloroform. The chloroform solution was then concentrated to give polymer p(g2T-T)-a (X = S) or p(g2T-Se)-a (X = Se). The molecular weights are provided in Table 1 below. TABLE 1 Polymer Mn(kDa) Mw(kDa) PDI p(g2T-T)-a 30 62 2.1 p(g2T-Se)-a 52 130 2.5

[0111] V. Functionalization of THP and TMO Groups on Polymer Side Chains.

[0112] Semiconducting polymer p(g2T-T)-a or p(g2T-Se)-a was dissolved in chloroform. The solution was spin-coated on a n-octadecyltrimethoxysilane (“OTS”) layer modified substrate at 1000 rpm / min for 1 minute, and then annealed at 110°C for 1 minute in a nitrogen-filled glovebox. The precursor solution was prepared by dissolving the alkyne-attached precursor molecule (4-propargylthiomorpholine 1,1-dioxide or tetrahydro-2-(2-propynyloxy)-2H-pyran) (~2 mM), copper(I) bromide (~0.2 mM), and N,N,N,N,N-pentamethyldiethylenetriamine (“PMDETA,” ~2 mM) in nitrogen-gas-purged methanol in a vial in the glovebox. The solution was thoroughly mixed. The deposited conjugated polymer film on a substrate was submerged in the precursor solution for 12 – 16 hours to allow in-film side-chain functionalization to occur. Subsequently, the films were removed from the glovebox and washed with water and methanol several times. The films were blown to dry using nitrogen gas. FIG. 1 illustrates FTIR spectra showing the disappearance of the azide peak after side-chain functionalization.FIG. 2 illustrates depth-profiling XPS spectra showing S 2p and N 1s peaks for p(g2T-T)-a (top) and p(g2T-T)-TMO (bottom), showing TMO side-chain functionalization. FIG. 3 illustrates XPS spectra indicating successful functionalization of THP and TMO groups.

[0113] The side-chain functionalized semiconducting polymers are shown below:p(g2T-T)-TMO; and p(g2T-Se)-TMO.

[0114] Experiments below were performed in comparison to p(g2T-T) and p(g2T-Se) as controls:p(g2T-T); and p(g2T-Se).

[0115] VI. In Vitro Cell Viability Assay.

[0116] RAW 264.7 cells (60,000 cells per well) were incubated with various semiconducting polymer-coated SEBS substrates in a 48-well plate for 24 hours. The cell culture media was DMEM (Gibco) containing 10% heat-inactivated fetal bovine serum (“FBS”), 1 mM sodium pyruvate, 55 mM HEPES, and 1% penicillin-streptomycin. Then MTT assay and Live / Dead cell staining were conducted for cell viability assay. MTT assay was measured using a plate reader (Biotek) as illustrated in FIG. 4. Live / dead cell imaging was taken using EVOSTM M7000 imaging system (Invitrogen) and is illustrated in FIG. 5. The examples of semiconducting polymers of the present disclosure do not demonstrate significant cell toxicity, ensuring their potential as biomaterials.

[0117] VII. In Vivo Implantation Experiment.

[0118] The semiconducting polymer films (thickness of ~150 nm) were transferred onto both sides of O2-plasma-treated SEBS substrates (thickness of ~0.8 mm). Implants were prepared by punching the substrates into circular disks with diameters of 5 mm. The implants were sterilized using 70% ethanol and UV sterilization for 20 minutes each. During the implantation, the back skin of the mouse was depilated with a razor and disinfected with isopropyl alcohol tissue and povidone-iodine tissue. The backside skin of the mouse was minimally incised. The materials were implanted in the subcutaneous region. Then the incise was closed by a skin clip.

[0119] The semiconducting polymers of the present disclosure were implanted for periods of one and four weeks.

[0120] VIII. Tissue Staining and Imaging.

[0121] The harvested skins were incubated in 2% PFA for 2 days at 4°C for fixation. The fixed skins underwent a paraffin embedding process and were sectioned into 5 μm thickness. Masson’s trichrome staining was conducted by Human Tissue Resource Center, The University of Chicago. Bright-field imaging was conducted using EVOSTM M7000 imaging system (Invitrogen). As illustrated in FIG.6, after one week of implantation the collagen layer elicited by p(g2T-Se) polymer had a lower density than from the control p(g2T-T) polymer, indicating less inflammation. After four weeks of implantation with the fibrotic capsule fully developed, MT staining results illustrated in FIG. 7 show a collagen density of ~13% at the p(g2T-Se) polymer-tissue interface, marking a ~50% decrease from the collagen density of 25% from p(g2T-T). The side-chain functionalization on p(g2T-Se) with THP and TMO further lower collagen density by another 35% and 39%, respectively, as illustrated Figure FIG.8. The side- chain functionalization on p(g2T-Se) with THP and TMO lowered CD68 significantly, as a marker of macrophages, as illustrated in FIG. 9; significantly, as a marker of myofibroblasts, as illustrated in FIG.10. FIG. 11 illustrates a plot of the collagen density as a function of the distance from the implant surface to the tissue surface. FIG. 12 illustrates a bar graph of the areas under the curves (“AUC”) for each of the semiconducting polymer plots illustrated in FIG. 11.

[0122] The collagen layer was composed mostly of type I and type III collagens, so the observed trend for collagen density was further validated by quantifying mRNA expression levels for collagen types I and III in the tissue regions around the implants. As illustrated in FIGs. 13 and 14, including selenophene in the polymer backbone decreased the levels of both collagen types by approximately 20-40%. As illustrated in FIGs. 15 and 16, including THP or TMO side-chain functionalization resulted in overall decrease of the levels of collagen types to approximately 50-70%.

[0123] For fluorescence staining, the sectioned slide was submitted to a deparaffination process and perm / blocking process in (0.3 % Triton X-100, 1% BSA in PBS) for 3 hours at room temperature. The slides were washed with PBS three times and incubated in primary antibody solution (0.1% tween 20 in PBS) for overnight at 4°C. Then, the slides were washed with PBS three times and incubated in secondary antibody (solution) for 2 hours at room temperature, followed by washing with PBS three times. The slides were stained with dAPI and covered by mounting solution. Antibody information: Anti-alpha smooth muscle Actin antibody (EPR5368, abcam), CD68 Monoclonal Antibody (FA-11, Invitrogen), Donkey anti- Rat IgG (H+L) Alexa FluroTM 594 Secondary Antibody, and Goat anti-Rabbit IgG AlexaFluorTM 647 Secondary Antibody (Invitrogen). The fluorescence imaging was conducted using Olympus confocal microscopy imaging system. The results in FIGs. 17 and 18 illustrate that both the backbone and side-chain functionalization helped to suppress immune cell recruitments. Particularly, p(g2T-Se)-TMO achieved decreases in the populations of macrophages and myofibroblasts by about 68% and 79%, respectively, compared to p(g2T-T).

[0124] IX. In Vivo Cytokine / chemokine Expression Level.

[0125] The harvested mouse skin was chopped and added to T-PER (Thermofisher Scientific) containing protease inhibitor (Thermofisher Scientific). The skin lysis was conducted using Lysis Matrix D (MP Biomedicals) and recommended protocol. The lysis solution was centrifuged at 20k rcf, 4°C, for 20 minutes to remove tissue fragments. Cytokines or chemokines concentration in supernatants were measured using Legendplex (Biolegend) or ELISA (Invitrogen).

[0126] X. In Vitro Evaluation of the Inhibitory Effect on Inflammation Signals.

[0127] To study the inflammatory signaling mechanism of the suppressed FBR, the expression levels of mouse inflammation-related markers at the end of the four-week implantation.

[0128] RAW 264.7 cells (60,000 cells per well) were seeded to a 48-well plate and incubated in a cell incubator for 24 hours. The cell media was carefully exchanged with the cell media (5% DMSO) containing various doses of monomers or polymers for 6 hours. Then, LPS (final concentration, 25 ng / mL) was added to the cell media, and the cells were incubated for 12 hours for the stimulation of the inflammation signal. After the stimulation, the cells were fixed using BD Lyse / Fix buffer for 10 minutes at 37°C and subsequently permeabilized using BD Phosflow Perm Buffer III for 30 minutes at 4°C. The cells were stained with anti-pERK BV421 (clone: 6B8B69, Biolegend), anti-p-p38 PE (clone: A16016A, Biolegend), anti-iNOS Alexa FluroTM 488 (clone: CXNFT, Invitrogen), and anti-pJNK Alexa FluroTM 647 (clone: N9- 66, BD) overnight at 4°C (dilution factor was 1:50). The cells were acquired using BD LSR flow cytometer and data was analyzed using FlowJo (TreeStar).

[0129] The results indicated that including both the selenophene in the backbone, and the THP- and TMO-side-chain functionalization, downregulated the pro-inflammatory biomarkers,including: C-C chemokine receptor type 7 (“CCR7,” FIG. 19); interferon- -20); granulocyte-macrophage colony-stimulating factor (“GM-CSF,” FIG. 21); monocyte chemoattractant protein-1 (“MCP-1,” FIG. 22); interleukins (IL)-23 (FIG. 23), IL-6 (FIG.24),IL- 25), IL-27 (FIG. 26), IL-12p70 (FIG. 27), and IL- G. 28). At the same time,upregulations were observed for anti-inflammatory biomarkers, including IL-10 (FIG.29), andIL-4 (FIG. 30). Together, the results suggested that the selenophene backbone and immunomodulatory side-chain functionalization led to the recruitment or differentiation ofmacrophages in anti- -inflammatoryphenotypes

[0130] XI. In Vitro ROS Evaluation.

[0131] The cytokine analysis above suggested some changes in macrophage behaviors during FBR, so a group of in vitro tests were conducted by directly exposing selenophene and thiophene to macrophages. To activate the inflammatory behavior, lipopolysaccharide (“LPS”), an inflammatory activator of immune cells, was added into the cell culture media.

[0132] In the first group tests, RAW 264.7 macrophages were incubated in media with selenophene or thiophene small molecules of different concentrations. RAW 264.7 cells (30,000 cells per well) were seeded to a 96-well plate and incubated in a cell incubator for 24 hours. The cell media was carefully exchanged with the cell media (5% DMSO) containing monomers (final concentration was 1 mmol / L) for 6 hours. Then LPS (final concentration was 25 ng / mL) was added to the media, and the cells were incubated for 3 hours for stimulation of the inflammation signal. After the stimulation, the cells were washed using PBS twice and incubated with PBS containing 2’,7’-dichlorodihydrofluorescein diacetate (DCFH2-DA, final concentration was 5 μM) for 30 minutes. Then, the cells were washed using PBS twice and resuspended in a flow buffer (PBS with 2% FBS). The cells were acquired suing BD LSR flow cytometer and data was analyzed using FlowJo (TreeStar).

[0133] During the cell culture processes over time, serious cell toxicity was not observed even at the maximum treatment dose in the two groups, as illustrated in FIGs.31-34. After 12 hours, the inflammatory activities of macrophages were tracked by measuring the concentrations of several representative pro-inflammatory biomarkers in macrophages, including phospho-p38 (“p-p38”), phospho-extracellular signal-regulated kinases (“p-ERK”), nitric oxide synthase (“iNOS”), and phospho-c-Jun N-terminal Kinase (“p-JNK”). As illustrated in FIGs.35-42, the presence of selenophene suppressed the expression of the inflammatory biomarkers in a dose- dependent way, but no such effect was observed form thiophene.

[0134] The second group of in vitro tests compared p(g2T-Se) with p(g2T-T) polymers. RAW 264.7 cells (30,000 cells per well) were seeded to a 96-well plate and incubated in a cell incubator for 24 hours. The cell media was carefully exchanged with the cell media (5% DMSO) containing polymers (final concentration was 20 μg / L) for 6 hours. Then LPS (final concentration was 25 ng / mL) was added to the media, and the cells were incubated for 3 hoursfor stimulation of the inflammation signal. After the stimulation, the cells were washed using PBS twice and incubated with PBS containing 2’,7’-dichlorodihydrofluorescein diacetate (DCFH2-DA, final concentration was 5 μM) for 30 minutes. Then, the cells were washed using PBS twice and resuspended in a flow buffer (PBS with 2% FBS). The cells were acquired suing BD LSR flow cytometer and data was analyzed using FlowJo (TreeStar).

[0135] The in vitro tests demonstrated the effect of selenophene in the polymer backbone in suppressing the inflammatory behavior of macrophages, as illustrated in FIGs. 43-50.

[0136] XII. Organic Electrochemical Transistor (“OECT”) Fabrication and Characterization.

[0137] The electrical performance of immune-compatible designs of semiconductors was tested in OECT devices. A schematic of an OECT device is illustrated in FIG. 51. A glass substrate was cleaned with acetone, isopropyl alcohol, and water, successively. The source / drain gold electrodes (60-nanometer thick) were then patterned via e-beam evaporation with a metal shadow mask. The channel length (L) and width (W) were 200 μm and 4 mm, respectively. The semiconducting polymer films were transferred onto the channel area using a polydimethylsiloxane (“PDMS”) stamp. The electrolyte of 0.1 M NaCl in water was dropped on top of the channel. The gate electrode was served by Ag / AgCl. The performance of the OECTs was measured using Keithley 4200 in an ambient environment. The transconductance (1):where Id is the drain current, and Vg is the gate voltage. The charge-carrier mobility was measured using the constant gate current method.

[0138] FIG. 52 illustrates transfer characteristics of semiconducting polymers p(g2T-T), p(g2T-Se), p(g2T-Se)-THP, and p(g2T-Se)-TMO. The results of transconductance and charge- carrier mobility calculations demonstrated that selenophene in the polymer backbone resulted in a higher transconductance and mobility compared to a full thiophene polymer backbone, as illustrated in FIGs. 53-55. For the side-chain functionalization with THP and TMO, which are relatively sterically bulky, the steric hindrance effect may lead to a minor decrease in performance, but the charge-carrier mobility remained around 1.0 cm2·V-1·s-1for selenophene- containing backbones. The tetra-ethylene-glycol units in the polymer side-chains may provide some buffering of the steric bulk of the side chains.

[0139] By including selenophene in the backbone, compared to thiophene, a higher relative degree of crystallinity (“rDoC”) and smaller lamellar packing distance were obtained, as illustrated in FIG. 56. UV-Vis spectroscopy indicated a redshift for the absorption onset,indicating a decrease of the bandgap resulting from an improvement in structural ordering, as illustrated in FIG.57. After side-chain functionalization, both p(g2T-Se)-THP and p(g2T-Se)- TMO displayed decreased rDoC and increased lamellar packing distances relative to p(g2T- Se), which may have caused the slight decrease in electrical performance. However, UV-Vis spectra illustrated in FIG. 57 indicated that p(g2T-Se)-THP and p(g2T-Se)-TMO substantially preserved the short-range aggregation level.

[0140] Although the present disclosure has been described with reference to examples and the accompanying drawings, the present disclosure is not limited thereto, but may be variously modified and altered by those skilled in the art to which the present disclosure pertains without departing from the spirit and scope of the present disclosure.

[0141] The subject-matter of the disclosure may also relate, among others, to the following aspects:

[0142] A first aspect relates to an implantable bioelectronic semiconducting polymer comprising thiophene and / or selenophene.

[0143] A second aspect relates to the polymer of aspect 1, comprising a thiophene backbone.

[0144] A third aspect relates to the polymer of any preceding aspect, wherein the backbone comprises selenophene.

[0145] A fourth aspect relates to any preceding aspect, comprising side chains comprising oligo(ethylene glycol) units.

[0146] A fifth aspect relates to the polymer of aspect 4, comprising side chains comprising tri(ethylene glycol) units or tetra(ethylene glycol) units.

[0147] A sixth aspect relates to the polymer of any preceding aspect, comprising side chains comprising a terminal functional group selected from.

[0148] seventh aspect relates to the polymer of any preceding aspect, wherein the polymer is of formula (I):wherein X is S or Se; and wherein.

[0149] An eighth aspect relates to the polymer of any preceding aspect, wherein a charge- carrier mobility is about 1.0 cm2·V-1·s-1.

[0150] A ninth aspect relates to a film comprising the polymer of any preceding aspect coated on a substrate.

[0151] A tenth aspect relates to an organic electrochemical transistor (“OECT”), comprising a channel comprising the polymer of aspects 1 to 8.

[0152] An eleventh aspect relates to a method of preparing the polymer of aspects 1 to 8, comprising: heating a solution of an azido-substituted dibromo-bithiophene monomer of formula (II)and 2,5-bis(trialkylstannyl)thiophene or 2,5-bis(trialkylstannyl)selenophene, to provide an azido-substituted polymer of formula (III)wherein X is S or Se; depositing the polymer of formula (III) on a substrate to provide a coated substrate; and submerging the coated substrate in a precursor solution of an alkyne to provide the polymer.

[0153] A twelfth aspect relates to the method of aspect 11, wherein the alkyne is selected from.

[0154] A thirteenth aspect relates to a bioelectronic implant comprising a polymer of aspects 1 to 8 coated on a substrate.

[0155] In addition to the features mentioned in each of the independent aspects enumerated above, some examples may show, alone or in combination, the optional features mentioned in the dependent aspects and / or as disclosed in the description above and shown in the figures.

Claims

CLAIMS What is claimed is:

1. An implantable bioelectronic semiconducting polymer comprising thiophene and / or selenophene.

2. The polymer of claim 1, comprising a thiophene backbone.

3. The polymer of claim 1 or 2, wherein the backbone comprises selenophene.

4. The polymer of claims 1 to 3, comprising side chains comprising oligo(ethylene glycol) units.

5. The polymer of claim 4, comprising side chains comprising tri(ethylene glycol) units or tetra(ethylene glycol) units.

6. The polymer of claims 1 to 5, comprising side chains comprising a terminal7. The polymer of claims 1 to 6, wherein the polymer is of formula (I):wherein X is S or Se; andwherein .

8. The polymer of claims 1 to 7, wherein a charge-carrier mobility is about 1.0 cm2·V-1·s-1.

9. A film comprising the polymer of claims 1 to 8 coated on a substrate.

10. An organic electrochemical transistor (“OECT”), comprising a channel comprising the polymer of claims 1 to 8.

11. A method of preparing the polymer of claims 1 to 8, comprising: heating a solution of an azido-substituted dibromo-bithiophene monomer of formula (II)and 2,5-bis(trialkylstannyl)thiophene or 2,5-bis(trialkylstannyl)selenophene, to provide an azido-substituted polymer of formula (III)wherein X is S or Se; depositing the polymer of formula (III) on a substrate to provide a coated substrate; and submerging the coated substrate in a precursor solution of an alkyne to provide the polymer.

12. The method of claim 11, wherein the alkyne is selected from.

13. A bioelectronic implant comprising a polymer of claims 1 to 8 coated on a substrate.

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