提高神经导管生物活性的策略
Strategies to Improve the Biological Activity of Nerve Conduits
DOI: 10.12677/BP.2021.113003, PDF,  被引量   
作者: 陈晓莉, 汤晓璇, 顾心逸, 凌 珏*, 杨宇民：南通大学，教育部/江苏省神经再生重点实验室/神经再生协同创新中心，江苏 南通
关键词: 神经导管；仿生；微环境；周围神经修复； Nerve Conduits； Bionic； Microenvironment； Peripheral Nerve Regeneration
摘要: 随着组织工程学研究的不断深入，神经导管的研究也已从简单的初级制备过渡到高级的仿生和功能制备。越来越多的研究表明，由组织工程产品材料的表面特性构成的微环境对组织工程和器官再生具有重要影响。例如材料的表面拓扑在指导细胞行为方面起着非常重要的作用，包括细胞形态、细胞粘附、分化和轴突引导。神经营养因子也被尝试引入神经导管，这些神经营养因子可控制细胞的命运，轴突的生长和引导，树突结构和修剪，突触的形成和突触可塑；而外源性电刺激能促进细胞增殖、神经细胞分化、轴突生长和伸展，并促进神经营养因子的产生。仅仅依靠单一因素，很难达到修复长距离神经缺损的理想效果，而研制具有多种因素组合调控的人工神经移植物，或成为神经再生领域的新思路。
Abstract: The development of nerve conduits for repairing peripheral nerve injury is now focusing on their advanced bionic and multifunctional properties rather than the primary structures, as the continuous studies in tissue engineering field. More and more studies have shown that the microenvironment formed by the surface properties of biomaterials has an important impact on tissue regeneration. For example, the surface microstructure of materials plays a very important role in guiding cell behavior, including cell morphology, cell adhesion, differentiation and axon guidance. On the other hand, neurotrophic factors that are introduced in innerve conduits can also improve axon growth and guidance, dendritic structure and pruning, synapse formation and synaptic plasticity; moreover, exogenous electrical stimulation can promote cell proliferation, nerve cell differentiation, axon growth and the production of neurotrophic factors. However, successful repair of long-distance peripheral still remains challenges only relying on single factor; therefore, development of nerve conduits with multi-cues may shed some light on peripheral nerve regeneratıon.
文章引用：陈晓莉, 汤晓璇, 顾心逸, 凌珏, 杨宇民. 提高神经导管生物活性的策略[J]. 生物过程, 2021, 11(3): 19-29. https://doi.org/10.12677/BP.2021.113003

参考文献

[1] Rajaram, A., Chen, X.-B. and Schreyer, D.J. (2012) Strategic Design and Recent Fabrication Techniques for Bioengi-neered Tissue Scaffolds to Improve Peripheral Nerve Regeneration. Tissue Engineering Part B—Reviews, 18, 454-467. [Google Scholar] [CrossRef] [PubMed]
[2] Faroni, A., Mobasseri, S.A., Kingham, P.J. and Reid, A.J. (2015) Peripheral Nerve Regeneration: Experimental Strategies and Future Perspectives. Advanced Drug Delivery Reviews, 82-83, 160-167. [Google Scholar] [CrossRef] [PubMed]
[3] Tabakow, P., Jarmundowicz, W., Czapiga, B., Fortuna, W., Miedzybrodzki, R., Czyz, M., Huber, J., Szarek, D., Okurowski, S., Szewczyk, P., Gorski, A. and Raisman, G. (2013) Transplantation of Autologous Olfactory Ensheathing Cells in Complete Human Spinal Cord Injury. Cell Transplanta-tion, 22, 1591-1612. [Google Scholar] [CrossRef] 
[4] Mano, J.F., Sousa, R.A., Boesel, L.F., Neves, N.M. and Reis, R.L. (2004) Bloinert, Biodegradable and Injectable Polymeric Matrix Composites for Hard Tissue Replacement: State of the Art and Recent Developments. Composites Science and Technology, 64, 789-817. [Google Scholar] [CrossRef] 
[5] Scotti, C., Tonnarelli, B., Papadimitropoulos, A., Scherber-ich, A., Schaeren, S., Schauerte, A., Lopez-Rios, J., Zeller, R., Barbero, A. and Martin, I. (2010) Recapitulation of En-dochondral Bone Formation Using Human Adult Mesenchymal Stem Cells as a Paradigm for Developmental Engineer-ing. Proceedings of the National Academy of Sciences of the United States of America, 107, 7251-7256. [Google Scholar] [CrossRef] [PubMed]
[6] Moskow, J., Ferrigno, B., Mistry, N., Jaiswal, D., Bulsara, K., Ru-draiah, S. and Kumbar, S.G. (2019) Review: Bioengineering Approach for the Repair and Regeneration of Peripheral Nerve. Bioactive Materials, 4, 107-113. [Google Scholar] [CrossRef] [PubMed]
[7] Teixeira, A.I., Abrams, G.A., Bertics, P.J., Murphy, C.J. and Nealey, P.F. (2003) Epithelial Contact Guidance on Well-Defined Micro- and Nanostructured Substrates. Journal of Cell Science, 116, 1881-1892. [Google Scholar] [CrossRef] [PubMed]
[8] Cai, J., Peng, X.J., Nelson, K.D., Eberhart, R. and Smith, G.M. (2005) Permeable Guidance Channels Containing Microfilament Scaffolds Enhance Axon Growth and Maturation. Journal of Biomedical Materials Research Part A, 75, 374-386. [Google Scholar] [CrossRef] [PubMed]
[9] Liu, Q., Huang, J., Shao, H., Song, L. and Zhang, Y. (2016) Dual-Factor Loaded Functional Silk Fibroin Scaffolds for Peripheral Nerve Regeneration with the Aid of Neovascularization. RSC Advances, 6, 7683-7691. [Google Scholar] [CrossRef] 
[10] Tsimbouri, P., Gadegaard, N., Burgess, K., White, K., Reynolds, P., Herzyk, P., Oreffo, R. and Dalby, M.J. (2014) Nanotopographical Effects on Mesenchymal Stem Cell Morphology and Phenotype. Journal of Cellular Biochemistry, 115, 380-390. [Google Scholar] [CrossRef] [PubMed]
[11] Spivey, E.C., Khaing, Z.Z., Shear, J.B. and Schmidt, C.E. (2012) The Fundamental Role of Subcellular Topography in Peripheral Nerve Repair Therapies. Biomaterials, 33, 4264-4276. [Google Scholar] [CrossRef] [PubMed]
[12] Sun, M., McGowan, M., Kingham, P.J., Terenghi, G. and Downes, S. (2010) Novel Thin-Walled Nerve Conduit with Micro-grooved Surface Patterns for Enhanced Peripheral Nerve Repair. Journal of Materials Science-Materials in Medicine, 21, 2765-2774. [Google Scholar] [CrossRef] [PubMed]
[13] Mobasseri, A., Faroni, A., Minogue, B.M., Downes, S., Terenghi, G. and Reid, A.J. (2015) Polymer Scaffolds with Preferential Parallel Grooves Enhance Nerve Regenera-tion. Tissue Engineering Part A, 21, 1152-1162. [Google Scholar] [CrossRef] [PubMed]
[14] Wang, C.-Y., Zhang, K.-H., Fan, C.-Y., Mo, X.-M., Ruan, H.-J. and Li, F.-F. (2011) Aligned Natural-Synthetic Polyblend Nanofibers for Peripheral Nerve Regeneration. Acta Bio-materialia, 7, 634-643. [Google Scholar] [CrossRef] [PubMed]
[15] Zhang, K., Jinglei, W., Huang, C. and Mo, X. (2013) Fabrication of Silk Fibroin/P(LLA-CL) Aligned Nanofibrous Scaffolds for Nerve Tissue Engineering. Macromolecular Materials and Engineering, 298, 565-574. [Google Scholar] [CrossRef] 
[16] Mahairaki, V., Lim, S.H., Christopherson, G.T., Xu, L., Nasonkin, I., Yu, C., Mao, H.-Q. and Koliatsos, V.E. (2011) Nanofiber Matrices Promote the Neuronal Differentiation of Human Embryonic Stem Cell-Derived Neural Precursors in Vitro. Tissue Engineering Part A, 17, 855-863. [Google Scholar] [CrossRef] [PubMed]
[17] Zheng, J., Kontoveros, D., Lin, F., Hua, G., Reneker, D.H., Becker, M.L. and Willits, R.K. (2015) Enhanced Schwann Cell Attachment and Alignment Using One-Pot “Dual Click” GRGDS and YIGSR Derivatized Nanofibers. Biomacromolecules, 16, 357-363. [Google Scholar] [CrossRef] [PubMed]
[18] Xie, J., MacEwan, M.R., Li, X., Sakiyama-Elbert, S.E. and Xia, Y. (2009) Neurite Outgrowth on Nanofiber Scaffolds with Different Orders, Structures, and Surface Properties. Acs Nano, 3, 1151-1159. [Google Scholar] [CrossRef] [PubMed]
[19] Christopherson, G.T., Song, H. and Mao, H.-Q. (2009) The Influence of Fiber Diameter of Electrospun Substrates on Neural Stem Cell Differentiation and Proliferation. Biomaterials, 30, 556-564. [Google Scholar] [CrossRef] [PubMed]
[20] Newman, K.D., McLaughlin, C.R., Carlsson, D., Li, F., Liu, Y. and Griffith, M. (2006) Bioactive Hydrogel-Filament Scaffolds for Nerve Repair and Regeneration. International Journal of Artificial Organs, 29, 1082-1091. [Google Scholar] [CrossRef] [PubMed]
[21] Wang, X.D., Hu, W., Cao, Y., Yao, J., Wu, J. and Gu, X.S. (2005) Dog Sciatic Nerve Regeneration across a 30-mm Defect Bridged by a Chitosan/PGA Artificial Nerve Graft. Brain, 128, 1897-1910. [Google Scholar] [CrossRef] [PubMed]
[22] Yao, L., de Ruiter, G.C.W., Wang, H., Knight, A.M., Spinner, R.J., Yaszemski, M.J., Windebank, A.J. and Pandit, A. (2010) Controlling Dispersion of Axonal Regeneration Using a Mul-tichannel Collagen Nerve Conduit. Biomaterials, 31, 5789-5797. [Google Scholar] [CrossRef] [PubMed]
[23] Lundborg, G. and Kanje, M. (1996) Bioartificial Nerve Grafts. A Prototype. Scandinavian Journal of Plastic and Reconstructive Surgery and Hand Surgery, 30, 105-110. [Google Scholar] [CrossRef] [PubMed]
[24] Lundborg, G., Dahlin, L., Dohi, D., Kanje, M. and Terada, N. (1997) A New Type of “Bioartificial” Nerve Graft for Bridging Extended Defects in Nerves. Journal of Hand Surgery (Edinburgh, Scotland), 22, 299-303. [Google Scholar] [CrossRef] 
[25] Hsu, S.-H., Lu, P.S., Ni, H.-C. and Su, C.-H. (2007) Fabri-cation and Evaluation of Microgrooved Polymers as Peripheral Nerve Conduits. Biomedical Microdevices, 9, 665-674. [Google Scholar] [CrossRef] [PubMed]
[26] McWhorter, F.Y., Davis, C.T. and Liu, W.F. (2015) Physical and Mechanical Regulation of Macrophage Phenotype and Function. Cellular and Molecular Life Sciences, 72, 1303-1316. [Google Scholar] [CrossRef] [PubMed]
[27] Reeves, A.R.D., Spiller, K.L., Freytes, D.O., Vunjak-Novakovic, G. and Kaplan, D.L. (2015) Controlled Release of Cytokines Using Silk-Biomaterials for Macrophage Polarization. Bio-materials, 73, 272-283. [Google Scholar] [CrossRef] [PubMed]
[28] Naskar, D., Nayak, S., Dey, T. and Kundu, S.C. (2014) Non-Mulberry Silk Fibroin Influence Osteogenesis and Osteoblast-Macrophage Cross Talk on Titanium Based Surface. Scientific Reports, 4, Article No. 4745. [Google Scholar] [CrossRef] [PubMed]
[29] Cui, X., Wen, J., Zhao, X., Chen, X., Shao, Z. and Jiang, J.J. (2013) A Pi-lot Study of Macrophage Responses to Silk Fibroin Particles. Journal of Biomedical Materials Research Part A, 101, 1511-1517. [Google Scholar] [CrossRef] [PubMed]
[30] Galeotti, F. andicsova, A., Yunus, S. and Botta, C. (2012) Precise Surface Patterning of Silk Fibroin Films by Breath Figures. Soft Matter, 8, 4815-4821. [Google Scholar] [CrossRef] 
[31] Mitropoulos, A.N., Marelli, B., Ghezzi, C.E., Applegate, M.B., Partlow, B.P., Kaplan, D.L. and Omenetto, F.G. (2015) Transparent, Nanostructured Silk Fibroin Hydrogels with Tunable Me-chanical Properties. Acs Biomaterials Science & Engineering, 1, 964-970. [Google Scholar] [CrossRef] [PubMed]
[32] Wieringa, P., Tonazzini, I., Micera, S. and Cecchini, M. (2012) Nanotopography Induced Contact Guidance of the F11 Cell Line during Neuronal Differentiation: A Neuronal Model Cell Line for Tissue Scaffold Development. Nanotechnology, 23, Article ID: 275102. [Google Scholar] [CrossRef] [PubMed]
[33] Beduer, A., Vieu, C., Arnauduc, F., Sol, J.-C., Loubinoux, I. and Vaysse, L. (2012) Engineering of Adult Human Neural Stem Cells Differentiation through Surface Micropatterning. Biomaterials, 33, 504-514. [Google Scholar] [CrossRef] [PubMed]
[34] Wieringa, P.A., de Pinho, A.R.G., Micera, S., van Wezel, R.J.A. and Moroni, L. (2018) Biomimetic Architectures for Peripheral Nerve Repair: A Review of Biofabrication Strate-gies. Advanced Healthcare Materials, 7, Article ID: 1701164. [Google Scholar] [CrossRef] [PubMed]
[35] Li, X., Li, M., Sun, J., Zhuang, Y., Shi, J., Guan, D., Chen, Y. and Dai, J. (2016) Radially Aligned Electrospun Fibers with Continuous Gradient of SDF1 alpha for the Guidance of Neural Stem Cells. Small, 12, 5009-5018. [Google Scholar] [CrossRef] [PubMed]
[36] Park, S.Y., Ki, C.S., Park, Y.H., Lee, K.G., Kang, S.W., Kweon, H.Y. and Kim, H.J. (2015) Functional Recovery Guided by an Electrospun Silk Fibroin Conduit after Sciatic Nerve Injury in Rats. Journal of Tissue Engineering and Regenerative Medicine, 9, 66-76. [Google Scholar] [CrossRef] [PubMed]
[37] Wang, Y., Kong, Y., Zhao, Y., Feng, Q., Wu, Y., Tang, X., Gu, X. and Yang, Y. (2016) Electrospun, Reinforcing Network-Containing, Silk Fibroin-Based Nerve Guidance Conduits for Pe-ripheral Nerve Repair. Journal of Biomaterials and Tissue Engineering, 6, 53-60. [Google Scholar] [CrossRef] 
[38] Jeffries, E.M. and Wang, Y. (2012) Biomimetic Micropatterned Mul-ti-Channel Nerve Guides by Templated Electrospinning. Biotechnology and Bioengineering, 109, 1571-1582. [Google Scholar] [CrossRef] [PubMed]
[39] Yanagisawa, S., Zhu, Z., Kobayashi, I., Uchino, K., Tamada, Y., Tamura, T. and Asakura, T. (2007) Improving Cell-Adhesive Properties of Recombinant Bombyx mori Silk by Incorporation of Col-lagen or Fibronectin Derived Peptides Produced by Transgenic Silkworms. Biomacromolecules, 8, 3487-3492. [Google Scholar] [CrossRef] [PubMed]
[40] Widhe, M., Johansson, U., Hillerdahl, C.-O. and Hedhammar, M. (2013) Recombinant Spider Silk with Cell Binding Motifs for Specific Adherence of Cells. Biomaterials, 34, 8223-8234. [Google Scholar] [CrossRef] [PubMed]
[41] Schuh, C.M.A.P., Monforte, X., Hackethal, J., Redl, H. and Teuschl, A.H. (2016) Covalent Binding of Placental Derived Proteins to Silk Fibroin Improves Schwann Cell Adhe-sion and Proliferation. Journal of Materials Science—Materials in Medicine, 27, 188. [Google Scholar] [CrossRef] [PubMed]
[42] Musson, D.S., Naot, D., Chhana, A., Matthews, B.G., McIntosh, J.D., Lin, S.T.C., Choi, A.J., Callon, K.E., Dunbar, P.R., Lesage, S., Coleman, B. and Cornish, J. (2015) In Vitro Evalu-ation of a Novel Non-Mulberry Silk Scaffold for Use in Tendon Regeneration. Tissue Engineering Part A, 21, 1539-1551. [Google Scholar] [CrossRef] [PubMed]
[43] Yu, W.-M., Yu, H., Chen, Z.-L. and Strickland, S. (2009) Disruption of Laminin in the Peripheral Nervous System Impedes Nonmyelinating Schwann Cell Development and Impairs Nociceptive Sensory Function. Glia, 57, 850-859. [Google Scholar] [CrossRef] [PubMed]
[44] Plantman, S., Patarroyo, M., Fried, K., Domogatskaya, A., Tryggvason, K., Hammarberg, H. and Cullheim, S. (2008) Integrin-Laminin Interactions Controlling Neurite Outgrowth from Adult DRG Neurons in Vitro. Molecular and Cellular Neuroscience, 39, 50-62. [Google Scholar] [CrossRef] [PubMed]
[45] Deister, C., Aljabari, S. and Schmidt, C.E. (2007) Effects of Colla-gen 1, Fibronectin, Laminin and Hyaluronic Acid Concentration in Multi-Component Gels on Neurite Extension. Journal of Biomaterials Science—Polymer Edition, 18, 983-997. [Google Scholar] [CrossRef] [PubMed]
[46] Gardiner, N.J. (2011) Integrins and the Extracellular Matrix: Key Mediators of Development and Regeneration of the Sensory Nervous System. Developmental Neurobiology, 71, 1054-1072. [Google Scholar] [CrossRef] [PubMed]
[47] Romano, N.H., Madl, C.M. and Heilshorn, S.C. (2015) Ma-trix RGD Ligand Density and L1CAM-Mediated Schwann Cell Interactions Synergistically Enhance Neurite Outgrowth. Acta Biomaterialia, 11, 48-57. [Google Scholar] [CrossRef] [PubMed]
[48] Widhe, M., Shalaly, N.D. and Hedhammar, M. (2016) A Fibron-ectin Mimetic Motif Improves Integrin Mediated Cell Biding to Recombinant Spider Silk Matrices. Biomaterials, 74, 256-266. [Google Scholar] [CrossRef] [PubMed]
[49] Yang, Y.J., Kwon, Y., Choi, B.-H., Jung, D., Seo, J.H., Lee, K.H. and Cha, H.J. (2014) Multifunctional Adhesive Silk Fibroin with Blending of RGD-Bioconjugated Mussel Adhesive Protein. Biomacromolecules, 15, 1390-1398. [Google Scholar] [CrossRef] [PubMed]
[50] Zhang, N., He, L. and Wu, W. (2016) Self-Assembling Peptide Nano-fibrous Hydrogel as a Promising Strategy in Nerve Repair after Traumatic Injury in the Nervous System. Neural Regen-eration Research, 11, 717-718. [Google Scholar] [CrossRef] [PubMed]
[51] Xiao, W., Hu, X.Y., Zeng, W., Huang, J.H., Zhang, Y.G. and Luo, Z.J. (2013) Rapid Sciatic Nerve Regeneration of Rats by a Surface Modified Collagen-Chitosan Scaffold. Inju-ry—International Journal of the Care of the Injured, 44, 941-946. [Google Scholar] [CrossRef] [PubMed]
[52] Zhu, L., Wang, K., Ma, T., Huang, L., Xia, B., Zhu, S., Yang, Y., Liu, Z., Quan, X., Luo, K., Kong, D., Huang, J. and Luo, Z. (2017) Noncovalent Bonding of RGD and YIGSR to an Electrospun Poly(epsilon-Caprolactone) Conduit through Peptide Self-Assembly to Synergistically Promote Sciatic Nerve Regeneration in Rats. Advanced Healthcare Materials, 6, Article ID: 1600860. [Google Scholar] [CrossRef] [PubMed]
[53] Chen, S., Zhao, Y., Yan, X., Zhang, L., Li, G. and Yang, Y. (2019) PAM/GO/gel/SA Composite Hydrogel Conduit with Bioactivity for Repairing Peripheral Nerve Injury. Journal of Bio-medical Materials Research Part A, 107, 1273-1283. [Google Scholar] [CrossRef] [PubMed]
[54] Gordon, T. (2009) The Role of Neurotrophic Factors in Nerve Regeneration. Neurosurgical Focus, 26, E3. [Google Scholar] [CrossRef] 
[55] Rich, K.M., Alexander, T.D., Pryor, J.C. and Hollowell, J.P. (1989) Nerve Growth Factor Enhances Regeneration through Silicone Chambers. Experimental Neurology, 105, 162-170. [Google Scholar] [CrossRef] [PubMed]
[56] Yang, Y., Zhao, W., He, J., Zhao, Y., Ding, F. and Gu, X. (2011) Nerve Conduits Based on Immobilization of Nerve Growth Factor onto Modified Chitosan by Using Genipin as a Crosslinking Agent. European Journal of Pharmaceutics and Biopharmaceutics, 79, 519-525. [Google Scholar] [CrossRef] [PubMed]
[57] Fine, E.G., Decosterd, I., Papaloizos, M., Zurn, A.D. and Aebischer, P. (2002) GDNF and NGF Released by Synthetic Guidance Channels Support Sciatic Nerve Regeneration across a Long Gap. The European Journal of Neuroscience, 15, 589-601. [Google Scholar] [CrossRef] [PubMed]
[58] Zhang, H., Wang, K., Xing, Y. and Yu, Q. (2015) Ly-sine-Doped Polypyrrole/Spider Silk Protein/Poly(L-lactic) Acid Containing Nerve Growth Factor Composite Fibers for Neural Application. Materials Science & Engineering C—Materials for Biological Applications, 56, 564-573. [Google Scholar] [CrossRef] [PubMed]
[59] Catrina, S., Gander, B. and Madduri, S. (2013) Nerve Conduit Scaffolds for Discrete Delivery of Two Neurotrophic Factors. European Journal of Pharmaceutics and Biopharmaceu-tics, 85, 139-142. [Google Scholar] [CrossRef] [PubMed]
[60] Kapur, T.A. and Shoichet, M.S. (2004) Immobilized Concentration Gradients of Nerve Growth Factor Guide Neurite Outgrowth. Journal of Biomedical Materials Research Part A, 68, 235-243. [Google Scholar] [CrossRef] [PubMed]
[61] Johnson, B.N., Lancaster, K.Z., Zhen, G., He, J., Gupta, M.K., Kong, Y.L., Engel, E.A., Krick, K.D., Ju, A., Meng, F., Enquist, L.W., Jia, X. and McAlpine, M.C. (2015) 3D Printed Anatomical Nerve Regeneration Pathways. Advanced Functional Materials, 25, 6205-6217. [Google Scholar] [CrossRef] [PubMed]
[62] Moore, K., Macsween, M. and Shoichet, M. (2006) Immobilized Concentration Gradients of Neurotrophic Factors Guide Neurite Outgrowth of Primary Neurons in Macroporous Scaf-folds. Tissue Engineering, 12, 267-278. [Google Scholar] [CrossRef] [PubMed]
[63] Roy, J., Kennedy, T.E. and Costantino, S. (2013) Engineered Cell Culture Substrates for Axon Guidance Studies: Moving beyond Proof of Concept. Lab on a Chip, 13, 498-508. [Google Scholar] [CrossRef] [PubMed]
[64] Wheeler, B.C., Corey, J.M., Brewer, G.J. and Branch, D.W. (1999) Mi-crocontact Printing for Precise Control of Nerve Cell Growth in Culture. Journal of Biomechanical Engineering, 121, 73-78. [Google Scholar] [CrossRef] [PubMed]
[65] Adams, D.N., Kao, E.Y.C., Hypolite, C.L., Distefano, M.D., Hu, W.S. and Letourneau, P.C. (2005) Growth Cones Turn and Migrate up an Immobilized Gradient of the Laminin IKVAV Peptide. Journal of Neurobiology, 62, 134-147. [Google Scholar] [CrossRef] [PubMed]
[66] Tung, T.H. (2015) Clinical Strategies to Enhance Nerve Regeneration. Neural Regeneration Research, 10, 22-24. [Google Scholar] [CrossRef] [PubMed]
[67] Geremia, N.M., Gordon, T., Brushart, T.M., Al-Majed, A.A. and Verge, V.M.K. (2007) Electrical Stimulation Promotes Sensory Neuron Regeneration and Growth-Associated Gene Ex-pression. Experimental Neurology, 205, 347-359. [Google Scholar] [CrossRef] [PubMed]
[68] Kimura, K., Yanagida, Y., Haruyama, T., Kobatake, E. and Aizawa, M. (1998) Gene Expression in the Electrically Stimulated Differentiation of PC12 Cells. Journal of Biotechnol-ogy, 63, 55-65. [Google Scholar] [CrossRef] 
[69] Lu, M.-C., Ho, C.-Y., Hsu, S.-F., Lee, H.-C., Lin, J.-H., Yao, C.-H. and Chen, Y.-S. (2008) Effects of Electrical Stimulation at Different Frequencies on Regeneration of Tran-sected Peripheral Nerve. Neurorehabilitation and Neural Repair, 22, 367-373. [Google Scholar] [CrossRef] [PubMed]
[70] Lu, M.-C., Tsai, C.-C., Chen, S.-C., Tsai, F.-J., Yao, C.-H. and Chen, Y.-S. (2009) Use of Electrical Stimulation at Different Current Levels to Promote Recovery after Peripheral Nerve Injury in Rats. Journal of Trauma-Injury Infection and Critical Care, 67, 1066-1072. [Google Scholar] [CrossRef] 
[71] Yeh, C.-C., Lin, Y.-C., Tsai, F.-J., Huang, C.-Y., Yao, C.-H. and Chen, Y.-S. (2010) Timing of Applying Electrical Stimulation Is an Important Factor Deciding the Success Rate and Maturity of Regenerating Rat Sciatic Nerves. Neurorehabilitation and Neural Repair, 24, 730-735. [Google Scholar] [CrossRef] [PubMed]
[72] Li, L., Yu, M., Ma, P.X. and Guo, B. (2016) Electroactive De-gradable Copolymers Enhancing Osteogenic Differentiation from Bone Marrow Derived Mesenchymal Stem Cells. Journal of Materials Chemistry B, 4, 471-481. [Google Scholar] [CrossRef] 
[73] You, J.-O., Rafat, M., Ye, G.J.C. and Auguste, D.T. (2011) Nanoengi-neering the Heart: Conductive Scaffolds Enhance Connexin 43 Expression. Nano Letters, 11, 3643-3648. [Google Scholar] [CrossRef] [PubMed]
[74] Martins, A.M., Eng, G., Caridade, S.G., Mano, J.F., Reis, R.L. and Vun-jak-Novakovic, G. (2014) Electrically Conductive Chitosan/Carbon Scaffolds for Cardiac Tissue Engineering. Biom-acromolecules, 15, 635-643. [Google Scholar] [CrossRef] [PubMed]
[75] Kai, D., Prabhakaran, M.P., Jin, G. and Ramakrishna, S. (2011) Polypyr-role-Contained Electrospun Conductive Nanofibrous Membranes for Cardiac Tissue Engineering. Journal of Biomedical Materials Research Part A, 99, 376-385. [Google Scholar] [CrossRef] [PubMed]
[76] Mihardja, S.S., Sievers, R.E. and Lee, R.J. (2008) The Effect of Polypyr-role on Arteriogenesis in an Acute Rat Infarct Model. Biomaterials, 29, 4205-4210. [Google Scholar] [CrossRef] [PubMed]
[77] Das, S., Sharma, M., Saharia, D., Sarma, K.K., Sarma, M.G., Borthakur, B.B. and Bora, U. (2015) In Vivo Studies of Silk Based Gold Nano-Composite Conduits for Function-al Peripheral Nerve Regeneration. Biomaterials, 62, 66-75. [Google Scholar] [CrossRef] [PubMed]
[78] Altizer, A.M., Moriarty, L.J., Bell, S.M., Schreiner, C.M., Scott, W.J. and Borgens, R.B. (2001) Endogenous Electric Current Is Associated with Normal Development of the Ver-tebrate Limb. Developmental Dynamics: An Official Publication of the American Association of Anatomists, 221, 391-401. [Google Scholar] [CrossRef] [PubMed]
[79] Wu, Y., Wang, L., Guo, B., Shao, Y. and Ma, P.X. (2016) Electroactive Biodegradable Polyurethane Significantly Enhanced Schwann Cells Myelin Gene Expression and Neurotrophin Secretion for Peripheral Nerve Tissue Engineering. Biomaterials, 87, 18-31. [Google Scholar] [CrossRef] [PubMed]