Molecular Approach to Conjugated Polymers with Biomimetic

Article Cite This: Acc. Chem. Res. 2018, 51, 1581−1589

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Molecular Approach to Conjugated Polymers with Biomimetic Properties Paul Baek,†,‡ Lenny Voorhaar,†,‡ David Barker,† and Jadranka Travas-Sejdic*,†,‡ †

Polymer Electronics Research Centre, School of Chemical Sciences, University of Auckland, Auckland 1010, New Zealand The MacDiarmid Institute for Advanced Materials and Nanotechnology, Wellington 6140, New Zealand

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‡

CONSPECTUS: The field of bioelectronics involves the fascinating interplay between biology and human-made electronics. Applications such as tissue engineering, biosensing, drug delivery, and wearable electronics require biomimetic materials that can translate the physiological and chemical processes of biological systems, such as organs, tissues. and cells, into electrical signals and vice versa. However, the difference in the physical nature of soft biological elements and rigid electronic materials calls for new conductive or electroactive materials with added biomimetic properties that can bridge the gap. Soft electronics that utilize organic materials, such as conjugated polymers, can bring many important features to bioelectronics. Among the many advantages of conjugated polymers, the ability to modulate the biocompatibility, solubility, functionality, and mechanical properties through side chain engineering can alleviate the issues of mechanical mismatch and provide better interface between the electronics and biological elements. Additionally, conjugated polymers, being both ionically and electrically conductive through reversible doping processes provide means for direct sensing and stimulation of biological processes in cells, tissues, and organs. In this Account, we focus on our recent progress in molecular engineering of conjugated polymers with tunable biomimetic properties, such as biocompatibility, responsiveness, stretchability, self-healing, and adhesion. Our approach is general and versatile, which is based on functionalization of conjugated polymers with long side chains, commonly polymeric or biomolecules. Applications for such materials are wide-ranging, where we have demonstrated conductive, stimuli-responsive antifouling, and cell adhesive biointerfaces that can respond to external stimuli such as temperature, salt concentration, and redox reactions, the processes that in turn modify and reversibly switch the surface properties. Furthermore, utilizing the advantageous chemical, physical, mechanical and functional properties of the grafts, we progressed into grafting of the long side chains onto conjugated polymers in solution, with the vision of synthesizing solution-processable conjugated graft copolymers with biomimetic functionalities. Examples of the developed materials to date include rubbery and adhesive photoluminescent plastics, biomolecule-functionalized electrospun biosensors, thermally and dually responsive photoluminescent conjugated polymers, and tunable self-healing, adhesive, and stretchable strain sensors, advanced functional biocidal polymers, and filtration membranes. As outlined in these examples, the applications of these biomimetic, conjugated polymers are still in the development stage toward truly printable, organic bioelectronic devices. However, in this Account, we advocate that molecular engineering of conjugated polymers is an attractive approach to a versatile class of organic electronics with both ionic and electrical conductivity as well as mechanical properties required for next-generation bioelectronics. chemical functionalization.4 Due to the aforementioned properties, CPs have been extensively explored as promising materials in biomedical applications that require interaction and communication across an electronics−biological interface.5−8 For example, in their widespread use as biosensors, they are often used to both sense and transduce biorecognition events into optical or electronic signals.7 For tissue engineering, they can provide soft scaffolds to deliver electrical stimulation for growth or induce differentiation of tissues and cells.8 Lastly, CPs are also considered particularly advantageous in interfacing with the neural system as electrodes,9 modulated drug delivery

1. INTRODUCTION Organic electronic materials are well recognized for their obvious set of advantageous properties, the most valuable being synthesis by molecular design and ease of chemical functionalization.1 Conjugated polymers (CPs) are a class of organic polymeric materials with a unique set of optoelectronic properties. They can be reversibly transformed between insulating and (semi)conducting states by a redox process.2 Importantly, they are both electron and ion conductors, especially in aqueous media, where ion exchange is crucial for understanding the interaction between the biological entity and electronic material.3 Other advantages can be found in the biocompatibility, flexibility, and tunability of their optical, electronic, electrochemical, and mechanical properties through © 2018 American Chemical Society

Received: November 28, 2017 Published: June 13, 2018 1581

DOI: 10.1021/acs.accounts.7b00596 Acc. Chem. Res. 2018, 51, 1581−1589

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Accounts of Chemical Research

Figure 1. General scheme showing the chemical structures of CP backbones and monomers of polymeric side chain utilized, as well as the functionalization approaches undertaken to synthesize multifunctional CPs with biomimetic properties. The choice of side chain polymers governs the functionality to be added. For instance, grafting of biomolecules, such as cell adhesion peptides and DNA, renders CPs cell-adhesive15 or for use as sensing elements,7 while grafting of poly(acrylic acid), poly(n-butyl acrylate), or poly(acrylate urethane) provides stimuli-responsiveness (pH, for instance)16 (Adapted with permission from ref 16. Copyright 2013 American Chemical Society), dry adhesion17 (Adapted from ref 17. Copyright 2017 Elsevier), or stretchability18 (Reproduced with permission from ref 18. Copyright 2017 American Chemical Society), respectively.

systems,10 and flexible semiconductors and conductors for conformal bioelectronics.11 For these applications, various classes of CPs (as shown in Figure 1) have been utilized, where functionalization of CPs has been traditionally limited to short side chains. To date, short side chains have mainly served to afford recognition sites for biosensing7 or as means of improving the solubility to enable large-area fabrication of flexible and printed electronic devices.12 Our earlier work involved attachment of small substituent groups, such as ethylene glycol, carboxylic acid, or anionic or cationic moieties, as side chains onto a poly(phenylene vinylene) (PPV), which rendered them watersoluble for biosensing and optoelectronic applications.13,14 However, functionalization of CPs with long polymeric side chains is rather uncommon and presents opportunity to add new biomimetic properties. In this Account, we consider grafting approach to functionalized CPs in a broader context of current and future biomedical and bioelectronics applications, but focusing on development of solution-processable, multifunctional CPs with tunable biomimetic properties. Our focus has been on expanding our initial successes in derivatization of CPs to develop a general and versatile methodology for functionalization with polymeric side chains. Grafting of functional polymers imparts a range of novel properties onto CPs, including intrinsic biomimetic properties (stretchability, self-healing, and adhesion), as well as responsiveness to external stimuli (such as temperature and redox processes). We envision that all the desirable properties can be, in principle, imparted onto a single conjugated polymer chain. In particular, we take two general approaches toward fabrication of long-side chain grafted CPs,

grafting of polymers from CPs (1) deposited onto a surface and (2) in solution, where each approach is described in sections 2 and 3, respectively.

2. GRAFTING FROM CONJUGATED POLYMERS DEPOSITED ON SURFACES FOR SMART AND ELECTROACTIVE BIOINTERFACES Grafting of polymer brushes from CP films deposited onto surfaces can be used to tailor the surface properties of the polymer films for various biomedical applications, including biointerfaces.4 Here, the term “polymer brush” most commonly refers to densely grafted, flexible polymer chains on a surface. Our research on grafting functional polymer brushes onto CP surfaces was initially developed with a desire to design electrochemically responsive surfaces. For this approach, CP films can be synthesized chemically or electrochemically. When their deposition on surfaces is considered, it is more common to perform electrochemical polymerization deposition (Figure 2). The CP should, however, be derivatized with initiating sites for the polymeric brushes to be grown. Polymer brushes can be grown from the tethered initiating sites using controlled free radical polymerization techniques, such as atom transfer radical polymerization (ATRP) of various vinyl monomers. Particularly, conventional ATRP method, as well as new variants of “activator generated by electron transfer” (AGET) and “activator regenerated by electron transfer” (ARGET) that provide more tolerance to oxygen and use less catalysts,19 can be employed. The living characteristics of these polymerization processes allow for controlled growth of polymers with low dispersity and synthesis of polymeric blocks. Other polymer1582


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CPs in solution to afford solution-processable CP graft copolymers.

3. GRAFTING OF CONJUGATED POLYMERS IN SOLUTION FOR PHYSICOCHEMICAL PROPERTIES, FUNCTION, AND PROCESSABILITY 3.1. Molecular Engineering of CPs

Stretchable electronics, for example, if further combined with the ability to adhere to complex surfaces including skin,26 open unprecedented opportunities in medical devices, health monitoring, sensing, biointegrated electronic devices, and soft robotics.27 Self-healing, which is intrinsic to biological systems and well researched in applications of polymers,28 is only in the early stages of development for electronics.29 The aim of our molecular engineering approach to functionalized and solutionprocessable CPs is to develop polymeric materials that conduct electricity and possess “designer” biomimetic properties, such as stretchability, adhesiveness, and self-healing.30 We draw here on the aforementioned examples of grafting of polymeric side chains from CP surfaces, taking advantage of the chemical, physical, and mechanical properties of the grafts. This approach does present interesting challenges, such as preserving electroactivity and conductivity of the CP backbone upon grafting, but also calls for exciting explorations, for example, in understanding of the both side chain and CP backbone chain conformations in the copolymer and their effects on the material’s optical and electrical properties, both in solution and in thin films. Therefore, the key features of these materials can be found in facile solution-processability and tailoring of the properties through side chain engineering. Molecular design of CP-based graft copolymers for a desired application requires consideration of the grafting methodology. Advances in graft copolymer synthesis31 provide us here with three general approaches, comprising graf ting through, graf ting f rom, and graf ting to, as shown in Figure 3. For the synthesis of

Figure 2. General scheme showing an example of electrochemical polymerization of ATRP initiator-functionalized EDOT, followed by grafting of copolymer brushes comprising DEGMMA and PEGMMA via AGET ATRP.22 Reproduced from ref 22 . Copyright 2015Royal Society of Chemistry. Depending on the composition of the two ethylene glycol-containing acrylate monomers, these conductive brushes can provide antifouling properties.

ization techniques such as reversible addition−fragmentation chain transfer (RAFT)20,21 can also be employed. By utilizing the redox properties of CPs, we demonstrated that switching surface hydrophobicity, as a function of redox state of the CP backbone, can be achieved using either zwitterionic side chains or their block copolymers with a hydrophobic poly(methyl methacrylate) (PMMA) block.23,24 In addition to controlling fouling and interaction with biomolecules and cells, applications of such stimuli-responsive conducting surfaces can be extended to electrochemically controlled surface wetting.25 In another study, we showed that controlling environmental conditions, such as temperature and salt concentration of the electrolyte solution, can reversibility switch the polymer brush conformation grafted from electrochemically deposited poly(3,4-ethylene dioxythiophene) (PEDOT) film on a gold electrode, from swollen to collapsed and vice versa.22 These effects were useful in controlling fouling by serum proteins, tuning the surface from fouling to completely antifouling, depending on the copolymer brush composition of di(ethylene glycol) methyl ether methacrylate (DEGMMA) and poly(ethylene glycol) methyl ether methacrylate (PEGMMA) grafted onto PEDOT. This approach was expanded into the adhesion of fibroblast cells onto such surfaces, where changing the brush composition and incorporation of the cell adhesion RGD peptide converted the non-celladhesive surface into cell-adhesive.15 Other types of polymer brushes, such as poly(acrylic acid) (PAA), grafted from PEDOT, showed responsiveness to pH (as shown in Figure 1), where the collapse of the brushes upon changing the acidity, in turn, controlled the surface electrochemical activity. As a result, PAA grafted CP films showed preserved and even enhanced electroactivity.16 These examples demonstrate the promise of grafting of polymer brushes from CPs on surfaces. The approach is particularly useful when the CPs are not solution-processable, which necessitates depositing them directly onto conducting surfaces. To alleviate the problem of a majority of CPs being intractable, we have invested continuous efforts in grafting of

Figure 3. Schematic diagram presenting three main synthetic methods toward CP graft copolymers.

CP graft copolymers in solution, the choice is driven by the final polymer architecture and compatibility of the monomers or polymeric macroinitiators with the synthetic conditions. For example, the grafting through approach typically requires a soluble macromonomer, whereas the grafting from approach requires a soluble CP macroinitiator. For grafting to methodology, both the CP backbone and the polymeric brushes must be soluble. In the following paragraphs, we discuss the CP 1583


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adhesive characteristics of the grafts (Figure 4c,d), which were not inherent of the ungrafted CPs.17,35 Moreover, the produced materials showed enhancement of photoluminescence quantum yields in both solution and solid state, attributed to a separation of PPV and PPE chains by the PnBA side chains, thus inhibiting π-stacking. This exemplifies how polymer architecture of the grafted CPs may result in important consequences for the optoelectrical properties of the material and will be discussed further below. We further extended the principle to design intrinsically healable and stretchable CPs to afford the desirable biomimetic properties for wearable bioelectronics. Here, an ATRP initiatorfunctionalized poly(thiophene) (PTh) backbone was grafted with low Tg (9.5 °C) and hydrogen-bonding poly(acrylate urethane) (PAU) side chains of various lengths (Figure 5a).18

grafting procedures carried out in our research group for each of these approaches. The grafting from approach involves polymerization of monomers from a preformed macroinitiator consisting of a conjugated polymer backbone with distributed initiator functionality. The method provides control over the molecular weight of CP backbone prior to grafting, as well as the brush length as a function of polymerization time. Compared to other grafting approaches, grafting from is arguably the most direct route to multifunctional grafted copolymers owing to the availability of a wide range of monomers that can be incorporated.31 Following the examples of grafting from surfaces, we have extensively utilized ATRP for grafting of polymeric side chains in solution. Grafting of low glass transition (Tg) acrylic polymers onto CP by the grafting from approach is expected to afford copolymers with elastomeric or adhesive properties of the grafts, while preserving the optoelectrical properties of CP backbone. We demonstrated earlier that surface-initiated ATRP grafting of low Tg (−70 °C)32 poly(2-ethylhexyl acrylate) brushes from poly(dimethylsiloxane) (PDMS) substrates provided 2-fold improvement in dry adhesion of PDMS flat films and 6-fold when the underlying PDMS substrate was micropatterned.33 The adhesive force (units in Newtons) of the grafted polymeric brushes were measured by the nanoindentation technique.33 Alternatively, adhesion of polymeric films can be quantified as adhesion energy (in J/m2) by measuring the stress applied perpendicular to the plane of the film when films are subject to double-cantilever beam experiments, as an example.34 By grafting similarly low Tg (−46 °C) poly(n-butyl acrylate) (PnBA) from poly(phenylene vinylenes) (PPVs) (Figure 4a,b) and poly(phenylene ethynylenes) (PPEs) by ARGET ATRP, we have shown that the resulting copolymers are solution processable and displayed

Figure 5. (a) Graft copolymer design toward intrinsically stretchable and healable conjugated polymers, which involves grafting of PAU from a PTh backbone via ATRP. (b) Measure of softness (by Young’s modulus) and stretchability (strain-at-break) of PTh-graft-PAU as a function of PAU length and solvent quality of the polymer solution from which polymer films are cast. (c) Room temperature mechanical healing of graft copolymers measured by observing the diffusion of stacked polymer layers under scanning electron microscope.18 Adapted with permission from ref 18. Copyright 2017 American Chemical Society.

In comparison to molecularly stretchable and healable segmented CPs,36,37 our graft copolymer concept enables preservation of the inherent electronic structure of the CP backbone. Varying the molecular design parameters, such as grafting length and copolymer film deposition conditions (e.g., solvent quality), were shown to control the film properties, as well as enable one to systematically investigate the effects of these parameters on the final mechanical, electrical and

Figure 4. (a) Schematic diagram showing grafting of PnBA from a PPV backbone via ARGET ATRP. (b) Differential scanning calorigram showing low Tg of PPV-graft-PnBAs, similar to that of PnBA homopolymer. Adhesive properties of the graft copolymers demonstrated by (c) simple tape peel test under UV light and (d) weight test, where the drop cast film is adhered to a glass vial filled with deionized water.35 Adapted from ref 35. Copyright 2016 Elsevier. 1584


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Accounts of Chemical Research structural properties of the material. The length of the side chain was shown to play a crucial role in both physical and electrical properties. For instance, the graft copolymers became more stretchable (measured by strain) and softer (measured by low Young’s modulus) as the length of the side chains increased (Figure 5b). Furthermore, the use of a mixture of a good and poor solvents for the CP backbone for casting of the films dictated the graft copolymer structure. This was reflected in the enhanced electrical conductivity, stretchability, and healing abilities of the cast films. To evaluate structural healing of the polymeric films, scanning electron microscopy was employed as shown in Figure 5c. Alternatively, the efficiency of healing can be quantified by comparing the toughness (area under the stress−strain curve) of polymers before and after healing.38 Here and in other discussed work,18,39,40 we often space out the ATRP-initiator carrying monomers with either nonfunctionalized or differently functionalized monomers. This is desired for several purposes: first, incorporating such monomers alleviates the steric hindrances of acrylic monomers during the grafting process; second, these may significantly aid solubility of the CP macroinitiator for the grafting from approach; and last, controlling the grafting density through the “spacer monomer” allows synthesis of CP copolymer of low graft-density, which is considered important in preserving the electronic properties of the CP backbone. In the case of PTh-gPAUs, for example, ungrafted PTh macroinitiator containing 20% of ATRP-initiator carrying monomers (using 3-hexylthiophene as the spacer) had electrical conductivity of 5.2 S cm−1, while graft copolymers with PAU side chain degree of polymerization (DP) of 17 units still had appreciable conductivity of 0.02 S cm−1.18 This approach to functionalized CPs can be extended into synthesis of other multifunctional grafted CPs. Recently, we synthesized a range of termonomers of CPs based on thiophene phenylenes (ThPs)39 and pyrrole phenylenes (PyPs)41 that carry versatile functional sites on the central phenylene ring. These termonomers can be considered as “building blocks” of a CP backbone and are useful for further polymer modification (Figure 6). Their derivatization produced organic solvent soluble CPs, where, in particular, the termonomers bearing ATRP-initiating sites and an azide moiety proved to be useful for further functionalization. Here, the azide provides the additional option of functionalization by click chemistry.42 The click site can be used to functionalize these materials with biological motifs, such as cell adhesion peptides, which are useful in tissue engineering scaffolds and similar applications.43 Importantly, both click chemistry and ATRP chemistry are found to be complementary and orthogonal in nature and could be performed from the same CP backbone. Termonomers carrying ethylene glycol (EG) side chains or a methoxy group can also be used here to impart hydrophilicity, protein fouling, or spacing out of other termonomers of choice. Despite having long, chemically distinct polymeric grafts prepared by both click and ATRP chemistries, the resulting graft copolymers preserved the electrochemical properties of the parent CP.39 While the synthesis of the termonomers is nontrivial, once made they allow a myriad of CPs to be prepared simply via altering the choice and ratios of termonomers. The grafting through approach involves preparation of conventional polymer chains with end-functionalized CP monomer of a desired conjugated backbone, which are referred to as macromonomers. The macromonomers are then (co)polymerized with CP monomers to yield a graft

Figure 6. Schematic route to multifunctional CPs based on a library of ThPs.39 Reproduced from ref 39. Copyright 2015 Royal Society of Chemistry.

copolymer.31 Generally, this approach enables control over the molecular weight and dispersity of the preformed macromonomer, and it is commonly carried out via electropolymerization on an electrode surface rather than in solution. A common issue with macromonomers in the case of CPs is that the end-functionalized CP monomer would get buried within the entangled macromonomer chains, sterically hindering the electro- or chemical polymerization of the macromonomer with other CP monomers.31 Due to these reasons, synthesizing grafted CPs with long polymeric side chains using grafting through methodology is limiting. Somewhat outside the scope of soluble grafted CPs, we considered this approach in fabricating gene sensors based on CPs on electrodes.41,44 We electrochemically grafted through thiophene phenylene (ThP) and pyrrole phenylene (PyP) termonomers that carried covalently bound oligonucleotides (ON) with either an ethylene glycol functionalized ThP termonomer or pyrrole. The method provided a rapid immobilization of the probefunctionalized sensing films on electrodes that proved to provide highly sensitive, label-free, electrochemical gene sensing.41 The grafting to approach, on the other hand, entails covalent attachment of preformed polymer chains onto a CP backbone. This method provides excellent control over the molecular weight of the preformed polymer as well as the CP backbone as they are synthesized and characterized independently prior to grafting. A consideration here is the solubility of all of the components, particularly of the CP backbone. Additionally, this approach is appropriate when low grafting density is desired due to the steric hindrance of grafting to the CP backbone. Employing this approach, we utilized the click sites on our 1585


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Figure 7. (a) Fabrication and (b,c) sensor responses of electrospun, PAA-grafted PEDOT DNA sensor.44 Adapted from ref 44. Copyright 2018 Elsevier.

CPs are widely used in biosensing applications.7 In particular, CP-based electrochemical biosensors provide electrical, labelfree readouts, along with cost-effective fabrication.46 As previously discussed, functionalization of CP monomers with biological molecules, prior to CP sensing film deposition on electrodes41 using grafting through approach, provides a means of high-throughput gene sensing microarray fabrication. This bioprobe immobilization principle was further applied to a DNA sensor based on electrospun CP fibers with polyanionic PAA grafts (Figure 7a),44 where a detection limit of 1 aM for the non-Hodgkin lymphoma gene was achieved (Figure 7b), along with an exceptional selectivity toward one-base mismatched sequences (Figure 7c). Such selectivity was attributed to the electrostatic repulsion of target DNA sequences by the negatively charged PAA grafts.44 Stretchable bioelectronics offer numerous exciting opportunities in wearable and biomedical devices, including wearable electrocardiography47 and neural probes. 48 To provide mechanical compliance to soft tissues and organs, as well as comfort, mechanical flexibility and stretchability is paramount.1 Advances in engineering of CPs have demonstrated that CPs can be made stretchable for such applications.30 Approaches include embedding or compositing CPs with elastomers, such as poly(dimethylsiloxane) (PDMS), poly(imide) (PI), or poly(urethane) (PU).38,49 The concept of molecularly and intrinsically stretchable electronics, however, avoids difficulties arising from chemical incompatibility in conducting composites.30 In addition, intrinsically self-healing materials would improve durability of devices; a desirable characteristic for biomedical devices and

PThPs to graft thermoresponsive poly(2-n-propyl-2-oxazoline) (PnPropOx) chains after grafting of PEGMMA chains from ATRP-initiating sites that provided water solubility for the click reactions.45 The success of the grafting can be attributed to the sufficient spacing between the azide moieties and the neighboring grafted PEGMMA provided by the low grafting density. The final copolymer displayed characteristics of all of the components of the system, lower critical solution temperature behavior of PnPropOx, optical properties of the PThP, and water solubility of PEGMMA. 3.2. Applications

Here, we demonstrate that the added biomimetic properties through side chain engineering of CPs can be applied to biomedical and wearable electronic applications. In regard to stimuli-responsive CPs, we demonstrated that grafting of polymers from CP films produces functional electroactive surfaces that are responsive to various stimuli, such as pH, salt, or temperature.22 As previously mentioned, PEGMMA and DEGMMA copolymerized side chains grafted from a PEDOT surface showed dynamic switching of their conformation induced by the changes in temperature and salt concentration; which are dependent on the brush copolymer composition.22 Certain compositions of these brushes afforded protein antifouling from a serum solution and modulated fibroblast cell adhesion.15 On the other hand, multifunctional and photoluminescent PThP-graf t-PEGMMAs are water-soluble and thermoresponsive, due to additional grafting of PnPropOx, providing a water-based optical temperature indicator.45 1586


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need to “smarten up” this intriguing and unique class of polymeric materials, to make them processable and possess biomimetic characteristics, namely, soft, adhesive, self-healing, stretchable, and responsive. Our generic and facile approach to “designer” CPs with predetermined physiochemical properties entails grafting CPs with long, polymeric side chains that afford CP graft copolymers with features of both, the grafts and the CP backbone. The methodology provides solubility to CPs, solving a notorious problem of majority of CPs being intractable and therefore nonprocessable. To demonstrate processability, so far we have mainly considered solution-based processing, for example, spin coating, dip-coating, and electrospinning of grafted CPs; however, the processing characteristics are, to a greater extent, determined by the properties of the side chains; therefore, there is no reason why these materials cannot be processed by other means, such as extrusion or molding. An exciting area of research that is widely open is understanding and controlling the properties of such materials, where chemically distinct polymeric chains are bound in a single macromolecule. In particular, it is expected that these copolymers can undergo diverse self-assembly and supramolecular organization in solutions, at interfaces, and in thin films. Polymer architecture and environmental parameters will affect steric constraints and stacking, hydrogen bonding, electrostatic, and other interactions that would allow such polymers to adopt unique molecular structures and morphologies. These will, in turn, determine the optoelectronics and other physical properties of the materials, as discussed above in our example on the effect of solvent quality on the conformation and properties of PTh-g-PAU. Although CP graft copolymers cannot yet compete with the state-of-the-art performance of inorganic semiconductors or conductors embedded into elastomers (or made into composites thereof) in conventional electronic devices (e.g., field-effect transistors), functionalized CPs present great opportunities in bioelectronics due to the simplicity of lowcost processing, ease of adding chemical and biological functionalities, and tunability of optoelectronic, mechanical, and physical properties. In current research underway in our laboratory, we investigate grafting of cell-adhesive peptides, using click chemistry, from our highly soluble PThPs, where the resulting graft copolymer can be processed by electrospinning into porous 3D fiber mats. The electrospun mats present excellent biocompatible substrates for tissue engineering, with an observed improvement in cell proliferation compared to electrospun mats of the ungrafted PThPs. As highlighted by us and others,3 this field of applications of CPs is extremely interdisciplinary, and crossing the boundaries of science, engineering, biology, and medicine is essential. This is a nontrivial task, which requires learning new languages and skills for all participants involved.

implants.29 Graft copolymers present an ideal opportunity in that regard. There have been only a few reports on molecular design of intrinsically stretchable and healable materials based on CPs.18,36 Our recent and current efforts are directed to incorporating stretchability and healing in CPs by means of polymeric grafts. As previously mentioned, healable and stretchable, low Tg PTh-g-PAUs with hydrogen-bonding side chains were utilized in organic strain sensors when solution dipcoated onto a cotton gauze.18 The strain sensor’s characteristic depended on the solvent used for dip-coating, as the conformation of the graft copolymer depended on the solvent quality for both CP backbone and the grafts (Figure 8).

Figure 8. (a,b) Demonstration of organic strain sensor fabricated from PTh-g-PAU (48 = PAU DP), showing a clear difference in the electrical response (measured as a change of resistance in response to repetitive stretching from 0 to 100% strain) as a function of solvent quality, in which the polymers were dissolved.18 Adapted with permission from ref 18. Copyright 2017 American Chemical Society.

4. CONCLUSIONS Increased focus on CP functionalization may well underpin faster uptake of electronic polymers in devices that can be integrated with human bodies to monitor, modulate, and repair biological functions.1 CPs can be used to provide mixed ionic and electrical conductivity in aqueous media, while advanced functionalization of CPs enables tuning of their solubility, incorporates stimuli-responsive behavior, modulates cell adhesion, growth, and differentiation, and generally improves biocompatibility, all desirable traits in bioelectronics applications.1 In vivo biosensing,50 body- or organ-integrated conformal medical devices,51 2D and 3D tissue engineering scaffolds that sense and control cellular behavior,52 and organs-on-a-chip platforms53 are a few of the exciting and appropriate areas of application for organic bioelectronics, which will be complemented by current developments in stretchable and conformal electronic devices.54 New discovery of electroactive biomaterials, such as CPs, underpins such developments. CPs are “smart”, electroactive, and electrically and ionically conducting, thus they have potential to fulfill many expectations of future bioelectronics systems. However, to realize that promise, we

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. ORCID

David Barker: 0000-0002-3425-6552 Jadranka Travas-Sejdic: 0000-0002-1205-3770 Notes

The authors declare no competing financial interest. 1587


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Accounts of Chemical Research Biographies

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Paul Baek received his B.Sc. Honors in Chemistry in 2014 from University of Auckland, supervised under Prof. Jadranka Travas-Sejdic. He is currently pursuing a Ph.D. in Chemistry at University of Auckland. His main research interests are found in development of advanced electronic polymers for wearable electronic sensors and biomedical applications. Lenny Voorhaar received her B.Sc. and M.Sc. in Molecular Life Sciences from Wageningen University and obtained her Ph.D. in Organic and Macromolecular Chemistry from Ghent University under supervision of Prof. Richard Hoogenboom in 2015. She is currently working as a research fellow with A. Prof. Barker and Prof. TravasSejdic on the topic of stretchable and self-healing conducting polymers. David Barker is an Associate Professor in organic and medicinal chemistry at the School of Chemical Sciences at University of Auckland. His research interests focus on synthesis of a wide range of targets including biologically active natural products, novel therapeutic agents, and functional polymeric scaffolds. Jadranka Travas-Sejdic is a Professor at the School of Chemical Sciences, Director of the Polymer Electronics Research Centre at University of Auckland, and a principal investigator and the Functional Nanostructures theme Science Leader at MacDiarmid Institute for Advanced Materials and Nanotechnology, New Zealand. Her research interests are in the fields of advancing and applications of polymeric materials for biosensing and bioelectronics. She has authored over 250 publications, including 9 book chapters.

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ACKNOWLEDGMENTS We acknowledge University of Auckland, New Zealand, and Australian Institute of Nuclear Science and Engineering, Australia, for the Ph.D. scholarships for P.B. and the Royal Society of New Zealand (Marsden Fund, grant number 3708747) for financial support of this work.

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Molecular Approach to Conjugated Polymers with Biomimetic

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