Conductive Materials

Acknowledgements

5.2 Conductive Materials

Conductive materials used for biological applications mainly consist of con- ductive polymers, piezoelectric polymeric materials, novel conductive nano- materials including carbon nanotubes and graphene, and self-assembled conductive hydrogels.

Published on 03 May 2017 on http://pubs.rsc.org | doi:10.1039/9781788010542-00110

5.2.1   Conductive Polymers

Conductive polymers demonstrate outstanding performance for an effective combination of the electrical properties of metals and the physicochemical properties of organic polymers.³⁶ normally, conductive polymers are organic polymers composed of high electrical properties with loosely held electrons in their backbones, and doping is an essential process for obtaining high conductivity polymers.^37,38 they have generated extensive significance for many biomedical applications including cell adhesion, proliferation and dif- ferentiation regulated by electrical stimulation.^33,39–42 several different kinds of conductive polymers, such as polypyrrole (ppy), polyaniline (pani) and polythiophene derivatives, have been developed and investigated for their potential application in the field of tissue engineering.

5.2.1.1 Polypyrrole

polypyrrole (ppy) (Figure 5.1) is among the top most commonly investigated conductive polymers for electronic devices and chemical sensors because of its unique properties, including high conductivity, good chemical stability and ease of synthesis.^36,43–46

the immense potential ppy exhibits for biomedical applications is attributed to its excellent properties of biocompatibility in vitro and in vivo.^19,47–49 it has also been revealed to provide promising reinforcement for the adhesion and growth of various cells.22,37,50–52 due to its effect on cell behavior, ppy has been broadly studied in the biomedical and tissue engi- neering fields.

5.2.1.2 Polyaniline

polyaniline (pani) (Figure 5.2) is another common conductive polymer widely studied due to its simplicity of synthesis and good environmental stability.^53,54 Mattioli-Belmonte reported the good biocompatibility of pani both in vitro and in vivo for the first time.⁵⁵ since then, numerous studies have

Figure 5.1    Chemical structure of polypyrrole.

Figure 5.2    Chemical structure of polyaniline.

Published on 03 May 2017 on http://pubs.rsc.org | doi:10.1039/9781788010542-00110

reported the excellent biocompatibility of pani and its ability to improve cell growth.^56–58

establishing the biocompatibility of pani both in vivo and in vitro led to a new research focus on designing materials for tissue engineering appli- cations. therefore, pani-based composites were considered, observed and studied in various biomedical applications, particularly for scaffolds in tissue engineering.^59–64

5.2.1.3 Polythiophene Derivatives

polythiophene derivatives are another type of electrically conductive poly- mer investigated in the fields of biomedical and tissue engineering.^65–68 poly(3,4-ethylenedioxythiophene) (pedot) (Figure 5.3) is considered to be the leading type of polythiophene derivative with outstanding conductivity, stability and low redox potentials.^69–71 two important qualities that make pedot excellent for biosensing as well as bioengineering applications are its low inherent cytotoxicity and inflammatory response after implantation^72,73 pedot has been explored for use in cochlear implants, vision prosthesis, neural regeneration devices and neural recording electrodes. these studies have led to great discoveries currently being used in bioengineering applica- tions including neural electrodes, nerve grafts and heart muscle patches.^74–76

5.2.2   Piezoelectric Polymeric Materials

tissue engineering applications do not only rely on conductive polymers;

piezoelectric polymeric materials have also been considered.^34,77,78 the advantage of piezoelectric polymeric materials in biomedical applications is the delivery of an electrical stimulus without the need for an external power source. under mechanical strain, piezoelectric polymeric materials produce a transient surface charge by mechanical deformations.¹⁴

the piezoelectricity of poly(vinylidene fluoride) (pVdF) was first discovered by heiji.⁷⁹ its unique molecular structure led to a transient surface charge produced on the synthetic, semi-crystalline polymer with piezoelectric prop- erties (Figure 5.4). due to its flexibility and non-toxicity,^80–84 pVdF has been widely studied for many different biomedical applications fields,^85–87 espe- cially in tissue engineering applications, including bone, neural and muscle regeneration.^88–93

Figure 5.3    Chemical structure of polythiophene and poly(3,4-ethylenedioxythio- phene).

Published on 03 May 2017 on http://pubs.rsc.org | doi:10.1039/9781788010542-00110

5.2.3   Other Novel Conductive Nanomaterials

there has been a shift in research on conductive materials into the nanoscale since nanomaterials were found to have a large specific surface area that can efficiently support electron transfer. in the biomedical and bioengineering fields, conductive nanomaterials have been investigated and employed as biosensors,^94,95 neural probes^96,97 and for tissue engineering.^98,99 specifically, carbon nanotubes (Cnts) have shown significant capability in guiding the dif- ferentiation orientations of stem cells, as well as working as an extracellular matrix to provoke cellular attachment and growth.^100,101 another conductive nanomaterial is graphene, which has been observed to regenerate electroactive tissues. graphene exhibits many desirable advantages, such as good biocom- patibility and biostability, making it a particularly promising biomaterial.¹⁰²

5.2.3.1 Carbon Nanotubes

Carbon nanotubes (Cnts) have emerged as promising conductive nanoma- terials for biomedical applications based on their unique properties.100,103–107

specifically, they are conducting fillers integrated into non-conductive poly- mers. this process provides a material that can be used as a scaffold with structural reinforcement and electrical conductivity to direct cell behaviors and offer favorable conditions to induce proper cellular functions due to its nanoscale cues, texture and roughness. several studies have shown that Cnts can be excellent substrates for cell attachment and growth.^108–112

additionally, bioactive electrically conductive three-dimensional (3d) scaf- folds can be prepared for tissue engineering by coating polymers, bioglasses, or collagen with Cnts. Cnt coatings have become a promising method and have the potential to develop the upcoming generation of engineered mate- rials for biomedical applications.^113–117

5.2.3.2 Graphene

graphene, a two-dimensional monolayer of carbon atoms, is another com- mon type of conductive nanomaterial with intrinsic nanostructure electrical properties. due to these properties, graphene has been observed being used for various types of applications, including bioanalysis, tumor therapy and stem cell research.^118–123 In vitro studies have demonstrated exceptional sup- port of graphene-based nanomaterials for adhesion, proliferation and differ- entiation behavior for many stem cells.^124,125

Figure 5.4    Chemical structure of poly(vinylidene fluoride).

Published on 03 May 2017 on http://pubs.rsc.org | doi:10.1039/9781788010542-00110

3d graphene foams (3d-gF) are graphene derivatives with 3d porous struc- tures and electrical conductivity,¹²⁶ which may help in advancing tissue engi- neering, specifically for novel scaffolds. 3d-gF can possess topographical as well as chemical and electrical signals in one scaffold. this will help create a steady environment for neural tissue regeneration; of major significance in tissue engineering and biomedical applications.¹²⁷

5.2.4   Self-Assembled Conductive Hydrogels

self-assembled conductive hydrogels are a type of composite material rapidly emerging in biomedical applications due to their ability to combine the prop- erties and advantages of each constituent, as well as their unique molecular structure.¹²⁸ Following the first reported conductive hydrogels by gong et al.

in 1991,¹²⁹ several studies have been focused on applying conductive hydro- gels for biosensors,^130,131 drug delivery^132,133 and tissue engineering.^134–138 a few examples include a poly(2-hydroxyethyl methacrylate) (pheMa)/ppy hydrogel entrapped with oxidoreductase enzymes designed for glucose oxi- dase biosensing,¹³¹ pani-polyacrylamide conductive hydrogels synthesized for the fabrication of controlled drug release devices¹³³ and Cnt-incorpo- rated gelatin methacrylate (gelMa) hydrogels developed for cardiac tissue engineering.135,137,138

5.3   Biocompatibility and Biodegradation of