Highly Conductive Stretchable and Biocompatible Electrode–Hydrogel Hybrids for Advanced Tissue Engineering

Hydrogel-based, molecular permeable electronic devices are considered to be promising for electrical stimulation and recording of living tissues, either in vivo or in vitro. This study reports the fabrication of the first hydrogel-based devices that remain highly electrically conductive under substantial stretch and bending. Using a simple technique involving a combination of chemical polymerization and electropolymerization of poly (3,4-ethylenedioxythiophene) (PEDOT), a tight bonding of a conductive composite of PEDOT and polyurethane (PU) to an elastic double-network hydrogel is achieved to make fully organic PEDOT/PU-hydrogel hybrids. Their response to repeated bending, mechanical stretching, hydration-dessication cycles, storage in aqueous condition for up to 6 months, and autoclaving is assessed, demonstrating excellent stability, without any mechanical or electrical damage. The hybrids exhibit a high electrical conductivity of up to 120 S cm(-1) at 100% elongation. The adhesion, proliferation, and differentiation of neural and muscle cells cultured on these hybrids are demonstrated, as well as the fabrication of 3D hybrids, advancing the field of tissue engineering with integrated electronics.

[1]  Yonggang Huang,et al.  Electronic sensor and actuator webs for large-area complex geometry cardiac mapping and therapy , 2012, Proceedings of the National Academy of Sciences.

[2]  Yoshimi Tanaka,et al.  True Chemical Structure of Double Network Hydrogels , 2009 .

[3]  Matsuhiko Nishizawa,et al.  Conducting Polymer Microelectrodes Anchored to Hydrogel Films. , 2012, ACS macro letters.

[4]  R. Dennis,et al.  Functional evaluation of nerve-skeletal muscle constructs engineered in vitro , 2007, In Vitro Cellular & Developmental Biology - Animal.

[5]  Z. Suo,et al.  Highly stretchable and tough hydrogels , 2012, Nature.

[6]  Shoji Takeuchi,et al.  Three-dimensional neuron-muscle constructs with neuromuscular junctions. , 2013, Biomaterials.

[7]  L. Shea,et al.  Hydrogel design for supporting neurite outgrowth and promoting gene delivery to maximize neurite extension , 2012, Biotechnology and bioengineering.

[8]  E. Smela,et al.  Stretchable Electrodes with High Conductivity and Photo‐Patternability , 2007 .

[9]  J. Gong,et al.  Tuning of cell proliferation on tough gels by critical charge effect. , 2009, Journal of biomedical materials research. Part A.

[10]  C. Schmidt,et al.  A chemically polymerized electrically conducting composite of polypyrrole nanoparticles and polyurethane for tissue engineering. , 2011, Journal of biomedical materials research. Part A.

[11]  D. Moran,et al.  Conductive Core–Sheath Nanofibers and Their Potential Application in Neural Tissue Engineering , 2009, Advanced functional materials.

[12]  Benjamin C. K. Tee,et al.  Electronic Properties of Transparent Conductive Films of PEDOT:PSS on Stretchable Substrates , 2012 .

[13]  Herman H. Vandenburgh,et al.  A computerized mechanical cell stimulator for tissue culture: Effects on skeletal muscle organogenesis , 1988, In Vitro Cellular & Developmental Biology.

[14]  Alexander Kros,et al.  Poly(pyrrole) versus poly(3,4-ethylenedioxythiophene): implications for biosensor applications , 2005 .

[15]  X. Yu,et al.  A laminin and nerve growth factor-laden three-dimensional scaffold for enhanced neurite extension. , 1999, Tissue engineering.

[16]  Makoto Kanzaki,et al.  Accelerated de novo sarcomere assembly by electric pulse stimulation in C2C12 myotubes. , 2007, Experimental cell research.

[17]  Daryl R Kipke,et al.  Hybrid Conducting Polymer–Hydrogel Conduits for Axonal Growth and Neural Tissue Engineering , 2012, Advanced healthcare materials.

[18]  Stéphanie P. Lacour,et al.  Flexible and stretchable micro-electrodes for in vitro and in vivo neural interfaces , 2010, Medical & Biological Engineering & Computing.

[19]  David C. Martin,et al.  Electrochemical polymerization of conducting polymers in living neural tissue , 2007, Journal of neural engineering.

[20]  J. Rogers,et al.  Stretchable Electronics: Materials Strategies and Devices , 2008 .

[21]  H. Choi,et al.  Highly conductive, printable and stretchable composite films of carbon nanotubes and silver. , 2010, Nature nanotechnology.

[22]  K Stokes,et al.  Polyether polyurethanes for implantable pacemaker leads. , 1982, Biomaterials.

[23]  L. Poole-Warren,et al.  Thin film hydrophilic electroactive polymer coatings for bioelectrodes. , 2013, Journal of materials chemistry. B.

[24]  Gordon G Wallace,et al.  A Conducting‐Polymer Platform with Biodegradable Fibers for Stimulation and Guidance of Axonal Growth , 2009, Advanced materials.

[25]  Justin A. Blanco,et al.  Dissolvable films of silk fibroin for ultrathin conformal bio-integrated electronics. , 2010, Nature materials.

[26]  C. Schmidt,et al.  Biomimetic conducting polymer-based tissue scaffolds. , 2013, Current opinion in biotechnology.

[27]  Nigel H Lovell,et al.  Conductive hydrogels: mechanically robust hybrids for use as biomaterials. , 2012, Macromolecular bioscience.

[28]  Kinam Kim,et al.  Highly stretchable electric circuits from a composite material of silver nanoparticles and elastomeric fibres. , 2012, Nature nanotechnology.

[29]  Elise M. Stewart,et al.  A Single Component Conducting Polymer Hydrogel as a Scaffold for Tissue Engineering , 2012 .

[30]  Yonggang Huang,et al.  Materials and Mechanics for Stretchable Electronics , 2010, Science.

[31]  Heungsoo Shin,et al.  The stimulation of myoblast differentiation by electrically conductive sub-micron fibers. , 2009, Biomaterials.

[32]  N. Kotov,et al.  Stretchable nanoparticle conductors with self-organized conductive pathways , 2013, Nature.

[33]  Brian Litt,et al.  Flexible, Foldable, Actively Multiplexed, High-Density Electrode Array for Mapping Brain Activity in vivo , 2011, Nature Neuroscience.

[34]  H. Vandenburgh,et al.  Mechanical stimulation improves tissue-engineered human skeletal muscle. , 2002, American journal of physiology. Cell physiology.

[35]  L. Poole-Warren,et al.  Stiffness Quantification of Conductive Polymers for Bioelectrodes , 2014 .

[36]  Matsuhiko Nishizawa,et al.  Conducting polymer electrodes printed on hydrogel. , 2010, Journal of the American Chemical Society.

[37]  P. Tresco,et al.  Response of brain tissue to chronically implanted neural electrodes , 2005, Journal of Neuroscience Methods.

[38]  H. Vandenburgh,et al.  In vitro model for stretch-induced hypertrophy of skeletal muscle. , 1979, Science.

[39]  M. Nishizawa,et al.  Spatiotemporally controlled contraction of micropatterned skeletal muscle cells on a hydrogel sheet. , 2011, Lab on a chip.

[40]  Nigel H Lovell,et al.  Impact of co-incorporating laminin peptide dopants and neurotrophic growth factors on conducting polymer properties. , 2010, Acta biomaterialia.

[41]  K. West,et al.  Highly Stretchable and Conductive Polymer Material Made from Poly(3,4‐ethylenedioxythiophene) and Polyurethane Elastomers , 2007 .

[42]  Khoon S Lim,et al.  Conductive hydrogels with tailored bioactivity for implantable electrode coatings. , 2014, Acta biomaterialia.

[43]  C. McCaig,et al.  The direction of growth of differentiating neurones and myoblasts from frog embryos in an applied electric field. , 1981, The Journal of physiology.

[44]  Ron Weiss,et al.  Formation and optogenetic control of engineered 3D skeletal muscle bioactuators. , 2012, Lab on a chip.

[45]  T. Someya,et al.  A Rubberlike Stretchable Active Matrix Using Elastic Conductors , 2008, Science.

[46]  Adam W Feinberg,et al.  Engineered skeletal muscle tissue for soft robotics: fabrication strategies, current applications, and future challenges. , 2014, Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology.

[47]  R Langer,et al.  Stimulation of neurite outgrowth using an electrically conducting polymer. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[48]  C. Schmidt,et al.  Nerve Growth Factor-Immobilized Electrically Conducting Fibrous Scaffolds for Potential Use in Neural Engineering Applications , 2012, IEEE Transactions on NanoBioscience.

[49]  Daryl R. Kipke,et al.  Conducting-polymer nanotubes improve electrical properties, mechanical adhesion, neural attachment, and neurite outgrowth of neural electrodes. , 2010, Small.

[50]  Michael C. McAlpine,et al.  Graphene-based wireless bacteria detection on tooth enamel , 2012, Nature Communications.

[51]  T. Someya,et al.  Stretchable active-matrix organic light-emitting diode display using printable elastic conductors. , 2009, Nature materials.

[52]  Hiromu Yawo,et al.  Optically controlled contraction of photosensitive skeletal muscle cells , 2012, Biotechnology and bioengineering.

[53]  Gordon G Wallace,et al.  Skeletal muscle cell proliferation and differentiation on polypyrrole substrates doped with extracellular matrix components. , 2009, Biomaterials.

[54]  T. Kurokawa,et al.  Double‐Network Hydrogels with Extremely High Mechanical Strength , 2003 .

[55]  S. Sen,et al.  Matrix Elasticity Directs Stem Cell Lineage Specification , 2006, Cell.

[56]  Frank P T Baaijens,et al.  Effects of a combined mechanical stimulation protocol: Value for skeletal muscle tissue engineering. , 2010, Journal of biomechanics.

[57]  C. Bettinger,et al.  Biomaterials‐Based Electronics: Polymers and Interfaces for Biology and Medicine , 2012, Advanced healthcare materials.