Chitosan/gelatin porous scaffolds assembled with conductive poly(3,4-ethylenedioxythiophene) nanoparticles for neural tissue engineering.

Electroactive biomaterials are widely explored as scaffolds for nerve tissue regeneration. Poly(3,4-ethylenedioxythiophene) (PEDOT) is a conductive polymer that has been chosen to construct tissue engineered scaffolds because of its excellent conductivity and non-cytotoxicity. In the present study, an electrically conductive scaffold was prepared by assembling PEDOT on a chitosan/gelatin (Cs/Gel) porous scaffold surface via in situ interfacial polymerization. The hydrophilic Cs/Gel hydrogel was used as a template, and PEDOT nanoparticles were uniformly assembled on the scaffold surface. The static polymerization of the 3,4-ethylenedioxythiophene (EDOT) monomer at the interface between the aqueous phase and the organic phase was accompanied by the formation of the PEDOT-assembled Cs/Gel scaffolds. PEDOT/Cs/Gel scaffolds were characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), and Raman spectroscopy. The results confirmed the deposition of PEDOT nanoparticles with the mean diameter of 50 nm on the Cs/Gel scaffold channel surface. Compared to the Cs/Gel scaffold, the incorporation of PEDOT on the scaffold increased the electrical conductivity, hydrophilicity, mechanical properties and thermal stability, whereas decreased the water absorption and biodegradation. For biocompatibility, PEDOT/Cs/Gel scaffolds, especially the 2PEDOT/Cs/Gel scaffold group, significantly promoted neuron-like rat pheochromocytoma (PC12) cell adhesion and proliferation. The results of both the gene expression and protein level assessments suggested that the PEDOT-assembled Cs/Gel scaffold enhanced the PC12 cellular neurite growth with higher protein and gene expression levels. This is the first report on the construction of a conductive PEDOT/Cs/Gel porous scaffold via an in situ interfacial polymerization method, and the results demonstrate that it may be a promising conductive scaffold for neural tissue engineering.

[1]  Yu-Sheng Hsiao,et al.  Electrically tunable organic bioelectronics for spatial and temporal manipulation of neuron-like pheochromocytoma (PC-12) cells. , 2013, Biochimica et biophysica acta.

[2]  Shui Guan,et al.  Chitosan/gelatin porous scaffolds containing hyaluronic acid and heparan sulfate for neural tissue engineering , 2013, Journal of biomaterials science. Polymer edition.

[3]  M. Podda,et al.  Exposure to extremely low-frequency (50Hz) electromagnetic fields enhances adult hippocampal neurogenesis in C57BL/6 mice , 2010, Experimental Neurology.

[4]  A. Albertsson,et al.  Biodegradable and electrically conducting polymers for biomedical applications , 2013 .

[5]  D. Kaplan,et al.  Physical and biological regulation of neuron regenerative growth and network formation on recombinant dragline silks. , 2015, Biomaterials.

[6]  Hanry Yu,et al.  Peripheral nerve regeneration with sustained release of poly(phosphoester) microencapsulated nerve growth factor within nerve guide conduits. , 2003, Biomaterials.

[7]  Christine E Schmidt,et al.  Carboxylic acid-functionalized conductive polypyrrole as a bioactive platform for cell adhesion. , 2006, Biomacromolecules.

[8]  S. Cartmell,et al.  Conductive polymers: towards a smart biomaterial for tissue engineering. , 2014, Acta biomaterialia.

[9]  L. Scheideler,et al.  Enhancing surface free energy and hydrophilicity through chemical modification of microstructured titanium implant surfaces. , 2006, Journal of biomedical materials research. Part A.

[10]  P. Chu,et al.  Biodegradable poly-lactic acid based-composite reinforced unidirectionally with high-strength magnesium alloy wires. , 2015, Biomaterials.

[11]  Liguo Cui,et al.  In vitro studies on regulation of osteogenic activities by electrical stimulus on biodegradable electroactive polyelectrolyte multilayers. , 2014, Biomacromolecules.

[12]  B. F. Yousif,et al.  A review on the degradability of polymeric composites based on natural fibres , 2013 .

[13]  Liping Wang,et al.  Poly(3,4-ethylenedioxythiophene)/poly(styrenesulfonate)-poly(vinyl alcohol)/poly(acrylic acid) interpenetrating polymer networks for improving optrode-neural tissue interface in optogenetics. , 2012, Biomaterials.

[14]  David C. Martin,et al.  In situ polymerization of a conductive polymer in acellular muscle tissue constructs. , 2008, Tissue engineering. Part A.

[15]  Christine E Schmidt,et al.  Neural tissue engineering: strategies for repair and regeneration. , 2003, Annual review of biomedical engineering.

[16]  A. Albertsson,et al.  Adjustable degradation properties and biocompatibility of amorphous and functional poly(ester-acrylate)-based materials. , 2014, Biomacromolecules.

[17]  Yu-Sheng Hsiao,et al.  Organic Photovoltaics and Bioelectrodes Providing Electrical Stimulation for PC12 Cell Differentiation and Neurite Outgrowth. , 2016, ACS applied materials & interfaces.

[18]  Peter X. Ma,et al.  Conductive PPY/PDLLA conduit for peripheral nerve regeneration. , 2014, Biomaterials.

[19]  Tianqing Liu,et al.  Hyaluronic acid doped-poly(3,4-ethylenedioxythiophene)/chitosan/gelatin (PEDOT-HA/Cs/Gel) porous conductive scaffold for nerve regeneration. , 2017, Materials science & engineering. C, Materials for biological applications.

[20]  M. Prabhakaran,et al.  Biocompatibility evaluation of electrically conductive nanofibrous scaffolds for cardiac tissue engineering. , 2013, Journal of materials chemistry. B.

[21]  Z. Cui,et al.  Fabrication and characterization of conductive poly (3,4-ethylenedioxythiophene) doped with hyaluronic acid/poly (l-lactic acid) composite film for biomedical application. , 2017, Journal of bioscience and bioengineering.

[22]  X. Mo,et al.  Polypyrrole-coated poly(l-lactic acid-co-ε-caprolactone)/silk fibroin nanofibrous membranes promoting neural cell proliferation and differentiation with electrical stimulation. , 2016, Journal of materials chemistry. B.

[23]  B. Mamba,et al.  Chitosan-based nanomaterials: a state-of-the-art review. , 2013, International journal of biological macromolecules.

[24]  C. Soeller,et al.  Poly(3,4-ethylenedioxythiophene) and Polyaniline Bilayer Nanostructures with High Conductivity and Electrocatalytic Activity , 2008 .

[25]  P. Ma,et al.  Electroactive biodegradable polyurethane significantly enhanced Schwann cells myelin gene expression and neurotrophin secretion for peripheral nerve tissue engineering. , 2016, Biomaterials.

[26]  Fabrizio Gelain,et al.  Nanomaterials design and tests for neural tissue engineering. , 2013, Chemical Society reviews.

[27]  M. Shoichet,et al.  Controlling cell adhesion and degradation of chitosan films by N-acetylation. , 2005, Biomaterials.

[28]  K. Neoh,et al.  Electrical stimulation of adipose-derived mesenchymal stem cells in conductive scaffolds and the roles of voltage-gated ion channels. , 2016, Acta Biomaterialia.

[29]  Xu Jiang,et al.  Current applications and future perspectives of artificial nerve conduits , 2010, Experimental Neurology.

[30]  Guorui Jin,et al.  The electrically conductive scaffold as the skeleton of stem cell niche in regenerative medicine. , 2014, Materials science & engineering. C, Materials for biological applications.

[31]  Omid Akhavan,et al.  Graphene scaffolds in progressive nanotechnology/stem cell-based tissue engineering of the nervous system. , 2016, Journal of materials chemistry. B.

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

[33]  H. Deng,et al.  Progress on the morphological control of conductive network in conductive polymer composites and the use as electroactive multifunctional materials , 2014 .

[34]  Emily Chang,et al.  Novel Degradable Co-polymers of Polypyrrole Support Cell Proliferation and Enhance Neurite Out-Growth with Electrical Stimulation , 2010, Journal of biomaterials science. Polymer edition.

[35]  C. Schmidt,et al.  Synthesis and characterization of polypyrrole-hyaluronic acid composite biomaterials for tissue engineering applications. , 2000, Journal of biomedical materials research.

[36]  David F Williams,et al.  Neural tissue engineering options for peripheral nerve regeneration. , 2014, Biomaterials.

[37]  Alain Guignandon,et al.  The effect of RGD density on osteoblast and endothelial cell behavior on RGD-grafted polyethylene terephthalate surfaces. , 2009, Biomaterials.

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

[39]  Seeram Ramakrishna,et al.  Electrospun conducting polymer nanofibers and electrical stimulation of nerve stem cells. , 2011, Journal of bioscience and bioengineering.

[40]  C. Schmidt,et al.  Electrical stimulation of human mesenchymal stem cells on biomineralized conducting polymers enhances their differentiation towards osteogenic outcomes. , 2015, Journal of materials chemistry. B.

[41]  S. Madihally,et al.  3D conductive nanocomposite scaffold for bone tissue engineering , 2013, International journal of nanomedicine.

[42]  G. Vunjak‐Novakovic,et al.  Electrically Conductive Chitosan/Carbon Scaffolds for Cardiac Tissue Engineering , 2014, Biomacromolecules.

[43]  Sheng Feng,et al.  Aligned Electroactive TMV Nanofibers as Enabling Scaffold for Neural Tissue Engineering. , 2015, Biomacromolecules.

[44]  Shu Wang,et al.  Construction of a 3D rGO-collagen hybrid scaffold for enhancement of the neural differentiation of mesenchymal stem cells. , 2016, Nanoscale.

[45]  Q. Wei,et al.  Electrophoretic deposition of chitosan/gelatin coatings with controlled porous surface topography to enhance initial osteoblast adhesive responses. , 2016, Journal of materials chemistry. B.

[46]  Hossein Baharvand,et al.  Application of conductive polymers, scaffolds and electrical stimulation for nerve tissue engineering , 2011, Journal of tissue engineering and regenerative medicine.

[47]  Yan Xiong,et al.  Micro-Nanostructured Polyaniline Assembled in Cellulose Matrix via Interfacial Polymerization for Applications in Nerve Regeneration. , 2016, ACS applied materials & interfaces.

[48]  Uma Maheswari Krishnan,et al.  Development of biomaterial scaffold for nerve tissue engineering: Biomaterial mediated neural regeneration , 2009, Journal of Biomedical Science.

[49]  M. Elsabee,et al.  Chitosan based edible films and coatings: a review. , 2013, Materials science & engineering. C, Materials for biological applications.

[50]  F. Abbasi,et al.  Microstructure and characteristic properties of gelatin/chitosan scaffold prepared by a combined freeze-drying/leaching method. , 2013, Materials science & engineering. C, Materials for biological applications.

[51]  Benjamin Geiger,et al.  Cell interactions with hierarchically structured nano-patterned adhesive surfaces. , 2009, Soft matter.

[52]  Lei Lu,et al.  Electrical Stimulation to Conductive Scaffold Promotes Axonal Regeneration and Remyelination in a Rat Model of Large Nerve Defect , 2012, PloS one.

[53]  J. Dai,et al.  Three-dimensional graphene foam as a biocompatible and conductive scaffold for neural stem cells , 2013, Scientific Reports.

[54]  P. Dallas,et al.  Interfacial polymerization of conductive polymers: Generation of polymeric nanostructures in a 2-D space. , 2015, Advances in colloid and interface science.