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Polymeric scaffolds for three-dimensional culture of nerve cells: a model of peripheral nerve regeneration

  • Biomaterials for 3D Cell Biology Prospective Article
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Abstract

Understanding peripheral nerve repair requires the evaluation of three-dimensional (3D) structures that serve as platforms for 3D cell culture. Multiple platforms for 3D cell culture have been developed, mimicking peripheral nerve growth and function, in order to study tissue repair or diseases. To recreate an appropriate 3D environment for peripheral nerve cells, key factors are to be considered, including selection of cells, polymeric biomaterials to be used, and fabrication techniques to shape and form the 3D scaffolds for cellular culture. This review focuses on polymeric 3D platforms used for the development of 3D peripheral nerve cell cultures.

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References

  1. J.W. Griffin, M.V. Hogan, A.B. Chhabra, and D.N. Deal: Peripheral nerve repair and reconstruction. J. Bone Joint Surg.–Am. 95, 2144 (2013).

    Article  Google Scholar 

  2. H.E. Resnick, K.B. Stansberry, T.B. Harris, M. Tirivedi, K. Smith, P. Morgan, and A.I. Vinik: Diabetes, peripheral neuropathy, and old age disability. Muscle Nerve 25, 43 (2002).

    Article  Google Scholar 

  3. D. Grinsell and C.P. Keating: Peripheral nerve reconstruction after injury: a review of clinical and experimental therapies. Biomed. Res. Int. 2014, 698256 (2014).

    Article  CAS  Google Scholar 

  4. National Institute of Neurological Disorders and Stroke. Peripheral Neuropathy Fact Sheet (Bethesda, Maryland, 2014).

    Google Scholar 

  5. C.A. Taylor, D. Braza, J.B. Rice, and T. Dillingham: The incidence of peripheral nerve injury in extremity trauma. Am. J. Phys. Med. Rehabil. 87, 381 (2008).

    Article  Google Scholar 

  6. S.H. Choi, Y.H. Kim, M. Hebisch, C. Sliwinski, S. Lee, C. D’Avanzo, H. Chen, B. Hooli, C. Asselin, J. Muffat, J.B. Klee, C. Zhang, B.J. Wainger, M. Peitz, D.M. Kovacs, C.J. Woolf, S.L. Wagner, R.E. Tanzi, and D.Y. Kim: A three-dimensional human neural cell culture model of Alzheimer’s disease. Nature 515, 274 (2014).

    Article  CAS  Google Scholar 

  7. T. Alberio, L. Lopiano, and M. Fasano: Cellular models to investigate biochemical pathways in Parkinson’s disease. FEBS J. 279, 1146 (2012).

    Article  CAS  Google Scholar 

  8. M. Ravi, V. Paramesh, S.R. Kaviya, E. Anuradha, and F.D. Paul Solomon: 3D cell culture systems: advantages and applications. J. Cell. Physiol. 230, 16 (2015).

    Article  CAS  Google Scholar 

  9. The American Society for Cell Biology: 2014 ASCB/IFCB Meeting abstracts. Mol. Biol. Cell 25, 3987 (2014).

    Article  Google Scholar 

  10. G. Kempermann and F.H. Gage: New nerve cells for the adult brain. Sci. Am. 280, 48 (1998).

    Article  Google Scholar 

  11. B.D. Simons and H. Clevers: Strategies for homeostatic stem cell self-renewal in adult tissues. Cell 145, 851 (2011).

    Article  CAS  Google Scholar 

  12. R. Edmondson, J.J. Broglie, A.F. Adcock, and L. Yang: Three-dimensional cell culture systems and their applications in drug discovery and cell-based biosensors. Assay Drug Dev. Technol. 12, 207 (2014).

    Article  CAS  Google Scholar 

  13. B.L. Behan, D.G. DeWitt, D.R. Bogdanowicz, A.N. Koppes, S.S. Bale, and D.M. Thompson: Single-walled carbon nanotubes alter Schwann cell behavior differentially within 2D and 3D environments. J. Biomed. Mater. Res. A 96A, 46 (2011).

    Article  CAS  Google Scholar 

  14. A. Mobasseri, A. Faroni, B.M. Minogue, S. Downes, G. Terenghi, and A.J. Reid: Polymer scaffolds with preferential parallel grooves enhance nerve regeneration. Tissue Eng. A 21, 1152 (2015).

    Article  CAS  Google Scholar 

  15. L. Tian, M.P. Prabhakaran, and S. Ramakrishna: Strategies for regeneration of components of nervous system: scaffolds, cells and biomolecules. Regen. Biomater. 2, 31 (2015).

    Article  CAS  Google Scholar 

  16. R.J.S.R. Shane Tubbs, E. Rizk, M.M. Shoja, M. Loukas, and N. Barbaro: Nerves and Nerve Injuries: Vol 2: Pain, Treatment, Injury, Disease and Future Directions (Academic Press, London, United Kingdom, 2015).

    Google Scholar 

  17. D. Freeman: Top causes of chronic pain plus treatments to help overcome pain. http://www.webmd.com (2010).

    Google Scholar 

  18. F.-Y. Hsieh and S. Hsu: 3D bioprinting: a new insight into the therapeutic strategy of neural tissue regeneration. Organogenesis 11, 153 (2015).

    Article  Google Scholar 

  19. M. Georgiou, S.C.J. Bunting, H.A. Davies, A.J. Loughlin, J.P. Golding, and J.B. Phillips: Engineered neural tissue for peripheral nerve repair. Biomaterials 34, 7335 (2013).

    Article  CAS  Google Scholar 

  20. Y. Xu, Z. Zhang, X. Chen, R. Li, D. Li, and S. Feng: A silk fibroin/collagen nerve scaffold seeded with a co-culture of Schwann cells and adipose-derived stem cells for sciatic nerve regeneration. PLoS ONE 11, 1 (2016).

    Google Scholar 

  21. B.N. Johnson, K.Z. Lancaster, G. Zhen, J. He, M.K. Gupta, Y.L. Kong, E.A. Engel, K.D. Krick, A. Ju, F. Meng, L.W. Enquist, X. Jia, and M.C. McAlpine: 3D printed anatomical nerve regeneration pathways. Adv. Funct. Mater. 25, 6205 (2015).

    Article  CAS  Google Scholar 

  22. D. Angius, H. Wang, R.J. Spinner, Y. Gutierrez-Cotto, M.J. Yaszemeski, and A.J. Windebank: A systematic review of animal models used to study nerve regereration in tissue-engineered scaffolds. Biomaterials 33, 8034 (2013).

    Article  Google Scholar 

  23. G.R.D. Evans: Challenges to nerve regeneration. Semin. Surg. Oncol. 19, 312 (2000).

    Article  CAS  Google Scholar 

  24. Z. Yongqiang: Tissue engineering and peripheral nerve regeneration (III)—sciatic nerve regeneration with PDLLA nerve guide. Sci. China, Ser. B, Chem. 44, 419 (2001).

    Article  Google Scholar 

  25. L.G. Griffith and G. Naughton: Tissue engineering—current challenges and expanding opportunities. Science 295, 1009 (2002).

    Article  CAS  Google Scholar 

  26. X. Xm, V. Guénard, N. Kleitman, and B. Mb: Axonal regeneration into Schwann cell-seeded guidance channels grafted into transected adult rat spinal cord. J. Comp. Neurol. 351, 1995 (1995).

    Google Scholar 

  27. A. Rajaram, X.-B. Chen, and D.J. Schreyer: Strategic design and recent fabrication techniques for bioengineered tissue scaffolds to improve peripheral nerve regeneration. Tissue Eng. B, Rev. 18, 454 (2012).

    Article  CAS  Google Scholar 

  28. J.M. Walker: Methods in molecular biology. Life Sci. 531, 588 (2009).

    Google Scholar 

  29. J. Kiernan and R. Rajakumar: Barr’s the Human Nervous System: An Anatomical Viewpoint (Williams and Wilkins, Lippincott, 2009).

    Google Scholar 

  30. M. Griffin, M. Malahias, S. Hindocha, and K.S. Wasim: Peripheral nerve injury: principles for repair and regeneration. Open Orthop. J. 8, 199 (2014).

    Article  Google Scholar 

  31. E.A. Huebner and S.M. Strittmatter: Axon regeneration in the peripheral and central nervous systems. In Cell Biol. Axon, edited by E. Koenig (Springer Berlin Heidelberg, Berlin, Heidelberg, 2009), pp. 305–360.

    Chapter  Google Scholar 

  32. J.W. Griffin, R. George, and T. Ho: Macrophage systems in peripheral nerves. A review. J. Neuropathol. Exp. Neurol. 52, 553 (1993).

    Article  CAS  Google Scholar 

  33. M.G. Burnett and E.L. Zager: Pathophysiology of peripheral nerve injury: a brief review. Neurosurg. Focus 16, 1 (2004).

    Article  Google Scholar 

  34. J.T. Rutka, G. Apodaca, R. Stern, and M. Rosenblum: The extracellular matrix of the central and peripheral nervous systems: structure and function. J. Neurosurg. 69, 155 (1988).

    Article  CAS  Google Scholar 

  35. S. Carbonetto: The extracellular matrix of the nervous system. Trends Neurosci. 7, 382 (1984).

    Article  Google Scholar 

  36. S. Geuna, S. Raimondo, F. Fregnan, K. Haastert-Talini, and C. Grothe: In vitro models for peripheral nerve regeneration. Eur. J. Neurosci. 43, 287 (2016).

    Article  CAS  Google Scholar 

  37. P. Parikh, Y. Hao, M. Hosseinkhani, S.B. Patil, G.W. Huntley, M. Tessier-Lavigne, and H. Zou: Regeneration of axons in injured spinal cord by activation of bone morphogenetic protein/Smad1 signaling pathway in adult neurons. Proc. Natl. Acad. Sci. USA 108, E99 (2011).

    Article  Google Scholar 

  38. Z.-S. Yin, H. Zhang, W. Bo, and W. Gao: Erythropoietin promotes functional recovery and enhances nerve regeneration after peripheral nerve injury in rats. AJNR. Am. J. Neuroradiol. 31, 509 (2010).

    Article  CAS  Google Scholar 

  39. Z. Liu, W. Gao, Y. Wang, W. Zhang, H. Liu, and Z. Li: Neuregulin-1β regulates outgrowth of neurites and migration of neurofilament 200 neurons from dorsal root ganglial explants in vitro. Peptides 32, 1244 (2011).

    Article  CAS  Google Scholar 

  40. F. Gattazzo, A. Urciuolo, and P. Bonaldo: Extracellular matrix: a dynamic microenvironment for stem cell niche. Biochim. Biophys. Acta 1840, 2506 (2014).

    Article  CAS  Google Scholar 

  41. A. Subramanian, U.M. Krishnan, and S. Sethuraman: Development of biomaterial scaffold for nerve tissue engineering: biomaterial mediated neural regeneration. J. Biomed. Sci. 16, 108 (2009).

    Article  Google Scholar 

  42. D. Koch, W.J. Rosoff, J. Jiang, H.M. Geller, and J.S. Urbach: Strength in the periphery: growth cone biomechanics and substrate rigidity response in peripheral and central nervous system neurons. Biophys. J. 102, 452 (2012).

    Article  CAS  Google Scholar 

  43. P.J. Lein, C.D. Barnhart, and I.N. Pessah: In vitro neurotoxicology. Methods Mol. Biol. 758, 1 (2004).

    Google Scholar 

  44. A. Rahmani, A. Shoae-Hassani, P. Keyhanvar, D. Kheradmand, and A. Darbandi-Azar: Dehydroepiandrosterone stimulates nerve growth factor and brain derived neurotrophic factor in cortical neurons. Adv. Pharmacol. Sci. 2013, 506191 (2013).

    Google Scholar 

  45. L.A. Greene, A.S. Tischlert, and S.W. Kuffler: Establishment of a noradrenergic clonal line of rat adrenal pheochromocytoma cells which respond to nerve growth factor (sympathetic neurons/cell culture/catecholamines/differentiation/neurites). Cell Biol. 73, 2424 (1976).

    CAS  Google Scholar 

  46. S.H. Hsu, W.C. Kuo, Y.T. Chen, C.T. Yen, Y.F. Chen, K.S. Chen, W.C. Huang, and H. Cheng: New nerve regeneration strategy combining laminin-coated chitosan conduits and stem cell therapy. Acta Biomater. 9, 6606 (2013).

    Article  CAS  Google Scholar 

  47. P.M. Crapo, C.J. Medberry, J.E. Reing, S. Tottey, Y. van der Merwe, K.E. Jones, and S.F. Badylak: Biologic scaffolds composed of central nervous system extracellular matrix. Biomaterials 33, 3539 (2012).

    Article  CAS  Google Scholar 

  48. Z. Shi, H. Gao, J. Feng, B. Ding, X. Cao, S. Kuga, Y. Wang, L. Zhang, and J. Cai: In situ synthesis of robust conductive cellulose/polypyrrole composite aerogels and their potential application in nerve regeneration. Angew. Chemie–Int. Ed. 53, 5380 (2014).

    Article  CAS  Google Scholar 

  49. G. Li, L. Zhang, C. Wang, X. Zhao, C. Zhu, Y. Zheng, Y. Wang, Y. Zhao, and Y. Yang: Effect of silanization on chitosan porous scaffolds for peripheral nerve regeneration. Carbohydr. Polym. 101, 718 (2014).

    Article  CAS  Google Scholar 

  50. C.J. Pateman, A.J. Harding, A. Glen, C.S. Taylor, C.R. Christmas, P.P. Robinson, S. Rimmer, F.M. Boissonade, F. Claeyssens, and J.W. Haycock: Nerve guides manufactured from photocurable polymers to aid peripheral nerve repair. Biomaterials 49, 77 (2015).

    Article  CAS  Google Scholar 

  51. M.F.B. Daud, K.C. Pawar, F. Claeyssens, A.J. Ryan, and J.W. Haycock: An aligned 3D neuronal-glial co-culture model for peripheral nerve studies. Biomaterials 33, 5901 (2012).

    Article  CAS  Google Scholar 

  52. J.I. Kim, T.I. Hwang, L.E. Aguilar, C.H. Park, and C.S. Kim: A controlled design of aligned and random nanofibers for 3D Bi-functionalized nerve conduits fabricated via a novel electrospinning set-up. Sci. Rep. 6, 23761 (2016).

    Article  CAS  Google Scholar 

  53. C.M.A.P. Schuh, T.J. Morton, A. Banerjee, C. Grasl, H. Schima, R. Schmidhammer, H. Redl, and D. Ruenzler: Activated Schwann cell-like cells on aligned fibrin-poly(lactic-co-glycolic acid) structures: a novel construct for application in peripheral nerve regeneration. Cells Tissues Org. 200, 287 (2015).

    Article  Google Scholar 

  54. A. Wang, Z. Tang, I.-H. Park, Y. Zhu, S. Patel, G.Q. Daley, and S. Li: Induced pluripotent stem cells for neural tissue engineering. Biomaterials 32, 5023 (2011).

    Article  CAS  Google Scholar 

  55. J.T. Oliveira, K. Mostacada, S. de Lima, and A.M.B. Martinez: Bone marrow mesenchymal stem cell transplantation for improving nerve regeneration. Int. Rev. Neurobiol. 108, 59 (2013).

    Article  CAS  Google Scholar 

  56. M. Tohill, C. Mantovani, M. Wiberg, and G. Terenghi: Rat bone marrow mesenchymal stem cells express glial markers and stimulate nerve regeneration. Neurosci. Lett. 362, 200 (2004).

    Article  CAS  Google Scholar 

  57. M.M. Najafabadi, V. Bayati, M. Orazizadeh, M. Hashemitabar, and F. Absalan: Impact of cell density on differentiation efficiency of rat adipose-derived stem cells into Schwann-like cells. Int. J. Stem Cells 9, 213 (2016).

    Article  CAS  Google Scholar 

  58. J.R. Higginson and S.C. Barnett: The culture of olfactory ensheathing cells (OECs)—a distinct glial cell type. Exp. Neurol. 229, 2 (2011).

    Article  Google Scholar 

  59. L. Nazareth, K.E. Lineburg, M.I. Chuah, J. Tello Velasquez, F. Chehrehasa, J.A. St John, and J.A.K. Ekberg: Olfactory ensheathing cells are the main phagocytic cells that remove axon debris during early development of the olfactory system. J. Comp. Neurol. 523, 479 (2015).

    Article  CAS  Google Scholar 

  60. P. Panni, I.A. Ferguson, I. Beacham, A. Mackay-Sim, J.A.K. Ekberg, and J.A. St John: Phagocytosis of bacteria by olfactory ensheathing cells and Schwann cells. Neurosci. Lett. 539, 65 (2013).

    Article  CAS  Google Scholar 

  61. N.A. Silva, M.J. Cooke, R.Y. Tam, N. Sousa, A.J. Salgado, R.L. Reis, and M.S. Shoichet: The effects of peptide modified gellan gum and olfactory ensheathing glia cells on neural stem/progenitor cell fate. Biomaterials 33, 6345 (2012).

    Article  CAS  Google Scholar 

  62. M.J. Ruitenberg, J. Vukovic, J. Sarich, S.J. Busfield, and G.W. Plant: Olfactory ensheathing cells: characteristics, genetic engineering, and therapeutic potential. J. Neurotrauma 23, 468 (2006).

    Article  Google Scholar 

  63. N. Mokarram, A. Merchant, V. Mukhatyar, G. Patel, and R.V. Bellamkonda: Effect of modulating macrophage phenotype on peripheral nerve repair. Biomaterials 33, 8793 (2012).

    Article  CAS  Google Scholar 

  64. J.P. Niemi, A. DeFrancesco-Lisowitz, L. Roldán-Hernández, J.A. Lindborg, D. Mandell, and R.E. Zigmond: A critical role for macrophages near axotomized neuronal cell bodies in stimulating nerve regeneration. J. Neurosci. 33, 16236 (2013).

    Article  CAS  Google Scholar 

  65. P. Chen, X. Piao, and P. Bonaldo: Role of macrophages in Wallerian degeneration and axonal regeneration after peripheral nerve injury. Acta Neuropathol. 130, 605 (2015).

    Article  CAS  Google Scholar 

  66. S. Parrinello, I. Napoli, S. Ribeiro, P.W. Digby, M. Fedorova, D.B. Parkinson, R.D.S. Doddrell, M. Nakayama, R.H. Adams, and A.C. Lloyd: EphB signaling directs peripheral nerve regeneration through Sox2-dependent Schwann cell sorting. Cell 143, 145 (2010).

    Article  CAS  Google Scholar 

  67. A.L. Cattin, J.J. Burden, L. Van Emmenis, F.E. MacKenzie, J.J.A. Hoving, N. Garcia Calavia, Y. Guo, M. McLaughlin, L.H. Rosenberg, V. Quereda, D. Jamecna, I. Napoli, S. Parrinello, T. Enver, C. Ruhrberg, and A.C. Lloyd: Macrophage-induced blood vessels guide schwann cell-mediated regeneration of peripheral nerves. Cell 162, 1127 (2015).

    Article  CAS  Google Scholar 

  68. L. Goers, P. Freemont, and K.M. Polizzi: Co-culture systems and technologies: taking synthetic biology to the next level. J. R. Soc. Interface 11, 20140065 (2014).

    Article  Google Scholar 

  69. D. Kraus, V. Boyle, N. Leibig, G.B. Stark, and V. Penna: The neuro-spheroid-a novel 3D in vitro model for peripheral nerve regeneration. J. Neurosci. Methods 246, 97 (2015).

    Article  CAS  Google Scholar 

  70. F. Gonzalez-Perez, E. Udina, and X. Navarro: Extracellular matrix components in peripheral nerve regeneration. Int. Rev. Neurobiol. 108, 257 (2013).

    Article  CAS  Google Scholar 

  71. Z.Z. Khaing and C.E. Schmidt: Advances in natural biomaterials for nerve tissue repair. Neurosci. Lett. 519, 103 (2012).

    Article  CAS  Google Scholar 

  72. R. Parenteau-Bareil, R. Gauvin, and F. Berthod: Collagen-based biomaterials for tissue engineering applications. Materials (Basel). 3, 1863 (2010).

    Article  CAS  Google Scholar 

  73. Y. Hu, Y. Wu, Z. Gou, J. Tao, J. Zhang, Q. Liu, T. Kang, S. Jiang, S. Huang, J. He, S. Chen, Y. Du, M. Gou, A. Faroni, S.A. Mobasseri, P.J. Kingham, A.J. Reid, A. Chhabra, S. Ahlawat, A. Belzberg, G. Andreseik, J. **e, X. Gu, F. Ding, D.F. Williams, J.H. Bell, J.W. Haycock, S. Kehoe, X.F. Zhang, D. Boyd, S.T. Koshy, T.C. Ferrante, S.A. Lewin, D.J. Mooney, J.Y. Chang, Y.S. Chen, K. Yue, C. Qi, X. Yan, C. Huang, A. Melerzanov, Y. Du, E. Gamez, J.W. Nichol, S. Suri, Y. Li, M.K. Kolar, P.J. Kingham, O. Heinemeyer, C.D. Reimers, B.N. Johnson, C.J. Pateman, D. Lin, S.V. Murphy, A. Atala, R.J. Morrison, F. Pati, S. Zhu, N. Hu, A.D. Widgerow, A.A. Salibian, S. Lalezari, G.R. Evans, S. Khalifian, D. Angius, C. Huang, Y. Niu, H. Xu, Y.Y. Hsueh, Y. He, G.H. Xue, J.Z. Fu, J.H. Park, J.W. Jung, H.W. Kang, D.W. Cho, M. Lee, J.C. Dunn, B.M. Wu, L. Yao, M.D. Bender, J.M. Bennett, R.L. Waddell, J.S. Doctor, K.G. Marra, L. Yao, K.L. Billiar, A.J. Windebank, A. Pandit, B. Cheng, S. Lu, X. Fu, L.E. Kokai, Y.C. Lin, N.M. Oyster, K.G. Marra, A. Chhabra, E.H. Williams, K.C. Wang, A.L. Dellon, J.A. Carrino, M. Wolf, K.M. Yamada, E. Cukierman, G. Liu, L.Y. Santiago, J. Clavijo-Alvarez, C. Brayfield, J.P. Rubin, K.G. Marra, C.C. Shen, Y.C. Yang, B.S. Liu, P.J. Kingham, P.G. di Summa, J.Y. Lee, B. Choi, B. Wu, M. Lee, T.C. Tseng, S.H. Hsu, J.R. Bain, S.E. Mackinnon, and D.A. Hunter: 3D-engineering of cellularized conduits for peripheral nerve regeneration. Sci. Rep. 6, 32184 (2016).

    Article  CAS  Google Scholar 

  74. P.C. Painter and M.M. Coleman: Essentials of Polymer Science and Engineering (DEStech Publications, Inc., Lancaster, Pennsylvania, 2009).

    Google Scholar 

  75. R.A. Brown and J.B. Phillips: Cell responses to biomimetic protein scaffolds used in tissue repair and engineering. Int. Rev. Cytol. 262, 75 (2007).

    Article  CAS  Google Scholar 

  76. M.P.E. Wenger, L. Bozec, M.A. Horton, and P. Mesquida: Mechanical properties of collagen fibrils. Biophys. J. 93, 1255 (2007).

    Article  CAS  Google Scholar 

  77. S. Suri, L.-H. Han, W. Zhang, A. Singh, S. Chen, and C.E. Schmidt: Solid freeform fabrication of designer scaffolds of hyaluronic acid for nerve tissue engineering. Biomed. Microdevices 13, 983 (2011).

    Article  CAS  Google Scholar 

  78. V. Vindigni, R. Cortivo, L. Iacobellis, G. Abatangelo, and B. Zavan: Hyaluronan benzyl ester as a scaffold for tissue engineering. Int. J. Mol. Sci. 10, 2972 (2009).

    Article  CAS  Google Scholar 

  79. S. Guan, X.-L. Zhang, X.-M. Lin, T.-Q. Liu, X.-H. Ma, and Z.-F. Cui: Chitosan/gelatin porous scaffolds containing hyaluronic acid and heparan sulfate for neural tissue engineering. J. Biomater. Sci. Polym. Ed. 24, 999 (2013).

    Article  CAS  Google Scholar 

  80. G. Kogan, L. Šoltés, R. Stern, and P. Gemeiner: Hyaluronic acid: a natural biopolymer with a broad range of biomedical and industrial applications. Biotechnol. Lett. 29, 17 (2007).

    Article  CAS  Google Scholar 

  81. S.J. Falcone, D. Palmeri, R.A. Berg, R. Galus, M. Antiszko, and P. Wlodarski: Biomedical applications of hyaluronic acid. Polysaccharides Drug Deliv. Pharm. Appl. 20, 155 (2006).

    Article  Google Scholar 

  82. M.N. Collins: Hyaluronic Acid for Biomedical and Pharmaceutical Applications (Smithers Rapra Technology, Shropshire, United Kingdom, 2014).

    Google Scholar 

  83. H. Nomura, C.H. Tator, and M.S. Shoichet: Bioengineered strategies for spinal cord repair. J. Neurotrauma 234, 496 (2006).

    Article  Google Scholar 

  84. C. Vepari and D.L. Kaplan: Silk as a biomaterial. Prog. Polym. Sci. 32, 991 (2007).

    Article  CAS  Google Scholar 

  85. B.-S. Liu, C.-H. Yao, S.-H. Hsu, T.-S. Yeh, Y.-S. Chen, and S.-T. Kao: A novel use of genipin-fixed gelatin as extracellular matrix for peripheral nerve regeneration. J. Biomater. Appl. 19, 21 (2004).

    Article  CAS  Google Scholar 

  86. X. Nie, M. Deng, M. Yang, L. Liu, Y. Zhang, and X. Wen: Axonal regeneration and remyelination evaluation of chitosan/gelatin-based nerve guide combined with transforming growth factor-β1 and Schwann cells. Cell Biochem. Biophys. 68, 163 (2014).

    Article  CAS  Google Scholar 

  87. M.F. Koudehi, A.A.I. Fooladi, K. Mansoori, Z. Jamalpoor, A. Amiri, and M.R. Nourani: Preparation and evaluation of novel nano-bioglass/gelatin conduit for peripheral nerve regeneration. J. Mater. Sci. Mater. Med. 25, 363 (2014).

    Article  CAS  Google Scholar 

  88. M. Ikeda, T. Uemura, K. Takamatsu, M. Okada, K. Kazuki, Y. Tabata, Y. Ikada, and H. Nakamura: Acceleration of peripheral nerve regeneration using nerve conduits in combination with induced pluripotent stem cell technology and a basic fibroblast growth factor drug delivery system. J. Biomed. Mater. Res. A 102, 1370 (2014).

    Article  Google Scholar 

  89. B.S. Liu: Fabrication and evaluation of a biodegradable proanthocyanidin-crosslinked gelatin conduit in peripheral nerve repair. J. Biomed. Mater. Res. A 87, 1092 (2008).

    Article  Google Scholar 

  90. Y. Chen, J. Chang, C. Cheng, F. Tsai, C. Yao, and B. Liu: An in vivo evaluation of a biodegradable genipin-cross-linked gelatin peripheral nerve guide conduit material. 26, 3911 (2005).

    CAS  Google Scholar 

  91. D. Arslantunali, T. Dursun, D. Yucel, N. Hasirci, and V. Hasirci: Peripheral nerve conduits: technology update. Med. Devices (Auckl). 7, 405 (2014).

    CAS  Google Scholar 

  92. D. Raafat, K. Von Bargen, A. Haas, and H.G. Sahl: Insights into the mode of action of chitosan as an antibacterial compound. Appl. Environ. Microbiol. 74, 3764 (2008).

    Article  CAS  Google Scholar 

  93. E. Khor and L.Y. Lim: Implantable applications of chitin and chitosan. Biomaterials 24, 2339 (2003).

    Article  CAS  Google Scholar 

  94. S.L. Chen, Z.G. Chen, H.L. Dai, J.X. Ding, J.S. Guo, N. Han, B.G. Jiang, H.J. Jiang, J. Li, S.P. Li, W.J. Li, J. Liu, Y. Liu, J.X. Ma, J. Peng, Y.D. Shen, G.W. Sun, P.F. Tang, G.H. Wang, X.H. Wang, L.B. **ang, R.G. **e, J.G. Xu, B. Yu, L.C. Zhang, P.X. Zhang, and S.L. Zhou: Repair, protection and regeneration of peripheral nerve injury. Neural Regen. Res. 10, 1777 (2015).

    Article  Google Scholar 

  95. Y. Yang, X. Gu, R. Tan, W. Hu, and X. Wang: Fabrication and properties of a porous chitin/chitosan conduit for nerve regeneration. Biotechnol. Lett. 2003, 1793 (2004).

    Article  Google Scholar 

  96. R.J. Nagao, S. Lundy, Z.Z. Khaing, and C.E. Schmidt: Functional characterization of optimized acellular peripheral nerve graft in a rat sciatic nerve injury model. Neurol. Res. 33, 600 (2011).

    Article  Google Scholar 

  97. International Consensus: Acellular matrices for the treatment of wounds. An Expert Work. Gr. Rev. 1, 16 pp. (2010).

  98. S. Hall: Axonal regeneration through acellular muscle grafts. J. Anat. 190, 57 (1997).

    Article  Google Scholar 

  99. J. Donaldson, R. Shi, and R. Borgens: Polyethylene glycol rapidly restores physiological functions in damaged sciatic nerves of guinea pigs. Neurosurgery 50, 147 (2002).

    Google Scholar 

  100. G.D. Bittner, K.K. Rokkappanavar, and J.D. Peduzzi: Application and implications of polyethylene glycol-fusion as a novel technology to repair injured spinal cords. Neural Regen. Res. 10, 1406 (2015).

    Article  CAS  Google Scholar 

  101. J. Zhu: Bioactive modification of poly (ethylene glycol) hydrogels for tissue engineering, biomaterials. 31, 4639 (2010).

    CAS  Google Scholar 

  102. A.J.R. Lasprilla, G.A.R. Martinez, B.H. Lunelli, A.L. Jardini, and R.M. Filho: Poly-lactic acid synthesis for application in biomedical devices—a review. Biotechnol. Adv. 30, 321 (2012).

    Article  CAS  Google Scholar 

  103. F. Yang, R. Murugan, S. Ramakrishna, X. Wang, Y.X. Ma, and S. Wang: Fabrication of nano-structured porous PLLA scaffold intended for nerve tissue engineering. Biomaterials 25, 1891 (2004).

    Article  CAS  Google Scholar 

  104. H.B. Wang, M.E. Mullins, J.M. Cregg, A. Hurtado, M. Oudega, M.T. Trombley, and R.J. Gilbert: Creation of highly aligned electrospun poly-L-lactic acid fibers for nerve regeneration applications. J. Neural Eng. 6, 16001 (2009).

    Article  Google Scholar 

  105. C. Guo, L. Zhou, and J. Lv: Effects of expandable graphite and modified ammonium polyphosphate on the flame-retardant and mechanical properties of wood flour-polypropylene composites. Polym. Polym. Compos. 21, 449 (2013).

    CAS  Google Scholar 

  106. H.K. Makadia, and S.J. Siegel: Poly lactic-co-glycolic acid (PLGA) as biodegradable controlled drug delivery carrier. Polymers (Basel). 3, 1377 (2011).

    Article  CAS  Google Scholar 

  107. K.-M. Lin, J. Shea, B.K. Gale, H. Sant, P. Larrabee, and J. Agarwal: Nerve growth factor released from a novel PLGA nerve conduit can improve axon growth. J. Micromech. Microeng. 26, 45016 (2016).

    Article  Google Scholar 

  108. T. Patrício, M. Domingos, A. Gloria, and P. Bártolo: Characterisation of PCL and PCL/PLA scaffolds for tissue engineering. Proc. CIRP 5, 110 (2013).

    Article  Google Scholar 

  109. S. Eshraghi and S. Das: Mechanical and microstructural properties of polycaprolactone scaffolds with one-dimensional, two-dimensional, and three-dimensional orthogonally oriented porous architectures produced by selective laser sintering. Acta Biomater. 6, 2467 (2010).

    Article  CAS  Google Scholar 

  110. S. Panseri, C. Cunha, J. Lowery, U. Del Carro, F. Taraballi, S. Amadio, A. Vescovi, and F. Gelain: Electrospun micro- and nanofiber tubes for functional nervous regeneration in sciatic nerve transections. BMC Biotechnol. 8, 39 (2008).

    Article  Google Scholar 

  111. L. Forciniti, J. Ybarra, M.H. Zaman, and C.E. Schmidt: Schwann cell response on polypyrrole substrates upon electrical stimulation. Acta Biomater. 10, 2423 (2014).

    Article  CAS  Google Scholar 

  112. H.C. Kang and K.E. Geckeler: Enhanced electrical conductivity of polypyrrole prepared by chemical oxidative polymerization: effect of the preparation technique and polymer additive. Polymer (Guildf). 41, 6931 (2000).

    Article  CAS  Google Scholar 

  113. N. Alhosseini, F. Moztarzadeh, M. Mozafari, S. Asgari, M. Dodel, A. Samadikuchaksaraei, S. Kargozar, and N. Jalali: synthesis and characterization of electrospun polyvinyl alcohol nanofibrous scaffolds modified by blending with chitosan for neural tissue engineering. Int. J. Nanomed. 7, 25 (2012).

    CAS  Google Scholar 

  114. M. Ye, P. Mohanty, and G. Ghosh: Morphology and properties of poly vinyl alcohol (PVA) scaffolds: impact of process variables. Mater. Sci. Eng. C 42, 289 (2014).

    Article  CAS  Google Scholar 

  115. G.E. Rutkowski and C.A. Heath: Development of a bioartificial nerve graft. II. Nerve regeneration in vitro. Biotechnol. Prog. 18, 373 (2002).

    Article  CAS  Google Scholar 

  116. W. Daly, L. Yao, D. Zeugolis, A. Windebank, and A. Pandit: A biomaterials approach to peripheral nerve regeneration: bridging the peripheral nerve gap and enhancing functional recovery. J. R. Soc. Interface 9, 202 (2012).

    Article  CAS  Google Scholar 

  117. J.H.A. Bell and J.W. Haycock: Next generation nerve guides: materials, fabrication, growth factors, and cell delivery. Tissue Eng. B, Rev. 18, 116 (2012).

    Article  CAS  Google Scholar 

  118. F. Fregnan, E. Ciglieri, P. Tos, A. Crosio, G. Ciardelli, F. Ruini, C. Tonda-Turo, S. Geuna, and S. Raimondo: Chitosan crosslinked flat scaffolds for peripheral nerve regeneration. Biomed. Mater. 11, 45010 (2016).

    Article  CAS  Google Scholar 

  119. S. Hui Hsu, T.T. Ho, and T.C. Tseng: Nanoparticle uptake and gene transfer efficiency for MSCs on chitosan and chitosan-hyaluronan substrates. Biomaterials 33, 3639 (2012).

    Article  Google Scholar 

  120. A. Busilacchi, A. Gigante, M. Mattioli-Belmonte, S. Manzotti, and R.A.A. Muzzarelli: Chitosan stabilizes platelet growth factors and modulates stem cell differentiation toward tissue regeneration. Carbohydr. Polym. 98, 665 (2013).

    Article  CAS  Google Scholar 

  121. C. Meyer, L. Stenberg, F. Gonzalez-Perez, S. Wrobel, G. Ronchi, E. Udina, S. Suganuma, S. Geuna, X. Navarro, L.B. Dahlin, C. Grothe, and K. Haastert-Talini: Chitosan-film enhanced chitosan nerve guides for long-distance regeneration of peripheral nerves. Biomaterials 76, 33 (2016).

    Article  CAS  Google Scholar 

  122. L. Stenberg and L.B. Dahlin: Gender differences in nerve regeneration after sciatic nerve injury and repair in healthy and in type 2 diabetic Goto-Kakizaki rats. BMC Neurosci. 15, 107 (2014).

    Article  Google Scholar 

  123. A.L.D. Kruse, H.T. Luebbers, K.W. Grätz, and J.A. Obwegeser: Factors influencing survival of free-flap in reconstruction for cancer of the head and neck: a literature review. Microsurgery 30, 242 (2010).

    Article  Google Scholar 

  124. S. Wrobel, S.C. Serra, S. Ribeiro-Samy, N. Sousa, C. Heimann, C. Barwig, C. Grothe, A.J. Salgado, and K. Haastert-Talini: In vitro evaluation of cell-seeded chitosan films for peripheral nerve tissue engineering. Tissue Eng. A 20, 2339 (2014).

    Article  CAS  Google Scholar 

  125. A.R. Nectow, K.G. Marra, and D.L. Kaplan: Biomaterials for the development of peripheral nerve guidance conduits. Tissue Eng. B, Rev. 18, 40 (2012).

    Article  CAS  Google Scholar 

  126. M. Uz, A.D. Sharma, P. Adhikari, D.S. Sakaguchi, and S.K. Mallapragada: Development of multifunctional films for peripheral nerve regeneration. Acta Biomater. 56, 141 (2017).

    Article  CAS  Google Scholar 

  127. K. Torigoe, H.F. Tanaka, H. Ohkochi, M. Miyasaka, H. Yamanokuchi, K. Yoshidad, and T. Yoshida: Hyaluronan tetrasaccharide promotes regeneration of peripheral nerve: in vivo analysis by film model method. Brain Res. 1385, 87 (2011).

    Article  CAS  Google Scholar 

  128. Q. Lin and W. Peng: 3D printing technologies for tissue engineering in ASME 2014. In Int. Design Engineering Technical Conf. & Computer Information in Engineering Conf. (2014).

    Google Scholar 

  129. S.V. Murphy and A. Atala: 3D bioprinting of tissues and organs. Nat. Biotechnol. 32, 773 (2014).

    Article  CAS  Google Scholar 

  130. B. He: Neural Engineering (Springer International Publishing, New York, 2013).

    Book  Google Scholar 

  131. R. Langer and J. Vacanti: Tissue engineering. Science 260, 920 (1993).

    Article  CAS  Google Scholar 

  132. R. El-Ayoubi, N. Eliopoulos, R. Diraddo, J. Galipeau, and A.M. Yousefi: Design and fabrication of 3D porous scaffolds to facilitate. Tissue Eng. A 14, 1037 (2008).

    Article  CAS  Google Scholar 

  133. J. Zhang, S. Zhao, Y. Zhu, Y. Huang, M. Zhu, C. Tao, and C. Zhang: Three-dimensional printing of strontium-containing mesoporous bioactive glass scaffolds for bone regeneration. Acta Biomater. 10, 2269 (2014).

    Article  CAS  Google Scholar 

  134. L. Koch, S. Kuhn, H. Sorg, M. Gruene, S. Schlie, R. Gaebel, B. Polchow, K. Reimers, S. Stoelting, N. Ma, P.M. Vogt, G. Steinhoff, and B. Chichkov: Laser printing of skin Cells and human stem cells. Tissue Eng. Part C Methods 16, 847 (2010).

    Article  CAS  Google Scholar 

  135. J.M. Anderson, A. Rodriguez, and D.T. Chang: Foreign body reaction to biomaterials. Semin. Immunol. Press 20, 86 (2008).

    Article  CAS  Google Scholar 

  136. J.R. Henstock, L.T. Canham, and S.I. Anderson: Silicon: the evolution of its use in biomaterials. Acta Biomater. 11, 17 (2015).

    Article  CAS  Google Scholar 

  137. H. Yurie, R. Ikeguchi, T. Aoyama, Y. Kaizawa, J. Ta**o, A. Ito, S. Ohta, H. Oda, H. Takeuchi, S. Akieda, M. Tsuji, K. Nakayama, and S. Matsuda: The efficacy of a scaffold-free Bio 3D conduit developed from human fibroblasts on peripheral nerve regeneration in a rat sciatic nerve model. PLoS ONE 12, e0171448 (2017).

    Article  Google Scholar 

  138. M.K. Danquah and R.I. Mahato: Emerging Trends in Cell and Gene Therapy (Springer International Publishing, New York, 2013).

    Book  Google Scholar 

  139. T.A. Kapur and M.S. Shoichet: Immobilized concentration gradients of nerve growth factor guide neurite outgrowth. J. Biomed. Mater. Res. A 68, 235 (2004).

    Article  Google Scholar 

  140. P. Soman, B.T.D. Tobe, J.W. Lee, A.A.M. Winquist, I. Singec, K.S. Vecchio, E.Y. Snyder, S. Chen, A. Hall, L. Jolla, A.A.M. Winquist, A. Hall, L. Jolla, and E.Y. Snyder: Three-dimensional scaffolding to investigate neuronal derivatives of human embryonic stem cells. Biomed. Microdevices 14, 829 (2013).

    Article  Google Scholar 

  141. B. Ratner, A. Hoffman, F. Schoen, and J. Lemons: Biomaterials Science: An Introduction to Materials in Medicine (Academic Press, London, United Kingdom, 2013). Chapter II, pp. 1147.

    Google Scholar 

  142. C.M. Murphy, A. Matsiko, M.G. Haugh, J.P. Gleeson, and F.J. O’Brien: Mesenchymal stem cell fate is regulated by the composition and mechanical properties of collagen-glycosaminoglycan scaffolds. J. Mech. Behav. Biomed. Mater. 11, 53 (2012).

    Article  CAS  Google Scholar 

  143. M.G. Haugh, C.M. Murphy, and F.J. O’Brien: Novel freeze-drying methods to produce a range of collagen-glycosaminoglycan scaffolds with tailored mean pore sizes. Tissue Eng. C, Methods 16, 887 (2010).

    Article  CAS  Google Scholar 

  144. N. Davidenko, T. Gibb, C. Schuster, S.M. Best, J.J. Campbell, C.J. Watson, and R.E. Cameron: Biomimetic collagen scaffolds with anisotropic pore architecture. Acta Biomater. 8, 667 (2012).

    Article  CAS  Google Scholar 

  145. R.A. Hortensius and B.A.C. Harley: The use of bioinspired alterations in the glycosaminoglycan content of collagen-GAG scaffolds to regulate cell activity. Biomaterials 34, 7645 (2013).

    Article  CAS  Google Scholar 

  146. G.J. Her, H.C. Wu, M.H. Chen, M.Y. Chen, S.C. Chang, and T.W. Wang: Control of three-dimensional substrate stiffness to manipulate mesenchymal stem cell fate toward neuronal or glial lineages. Acta Biomater. 9, 5170 (2013).

    Article  CAS  Google Scholar 

  147. P. Kang, M. Liao, M.R. Wester, J.S. Leeder, and R.E. Pearce: The stress relaxation characteristics of composite matrices etched to produce nanoscale surface features. Ratio 36, 490 (2010).

    Google Scholar 

  148. X Niu, X. Li, H. Liu, G. Zhou, Q. Feng, F. Cui, and Y. Fan: Homogeneous chitosan/poly(L-Lactide) composite scaffolds prepared by emulsion freeze-drying. J. Biomater. Sci. Polym. Ed. 23, 391 (2012).

    Article  CAS  Google Scholar 

  149. Z. Zhang and H. Cui: Biodegradability and biocompatibility study of poly(chitosan-g-lactic acid) scaffolds. Molecules 17, 3243 (2012).

    Article  CAS  Google Scholar 

  150. J. Kozłowska and A. Sionkowska: Effects of different crosslinking methods on the properties of collagen-calcium phosphate composite materials. Int. J. Biol. Macromol. 74, 397 (2015).

    Article  Google Scholar 

  151. C. Gaudillere and J.M. Serra: Freeze-casting: fabrication of highly porous and hierarchical ceramic supports for energy applications. Boletín la Soc. Española Cerámica y Vidr. 55, 45 (2016).

    Article  CAS  Google Scholar 

  152. U.G.K. Wegst, M. Schecter, A.E. Donius, and P.M. Hunger: Biomaterials by freeze casting. Phil. Trans. R. Soc. A 368, 2099 (2010).

    Article  CAS  Google Scholar 

  153. N.L. Francis, P.M. Hunger, A.E. Donius, B.W. Riblett, A. Zavaliangos, U.G.K. Wegst, and M.A. Wheatley: An ice-templated, linearly aligned chitosan-alginate scaffold for neural tissue engineering. J. Biomed. Mater. Res. A 101, 3493 (2013).

    Article  Google Scholar 

  154. J. **e, W. Liu, M.R. Macewan, P.C. Bridgman, and Y. **a: Neurite outgrowth on electrospun nano fibers with uniaxial alignment: the effects of fiber density, surface coating, and supporting substrate ACS Nano 8, 1878 (2015).

    Article  Google Scholar 

  155. Y. tae Kim, V.K. Haftel, S. Kumar, and R.V. Bellamkonda: The role of aligned polymer fiber-based constructs in the bridging of long peripheral nerve gaps. Biomaterials 29, 3117 (2008).

    Article  CAS  Google Scholar 

  156. Z.M. Huang, Y.Z. Zhang, M. Kotaki, and S. Ramakrishna: A review on polymer nanofibers by electrospinning and their applications in nanocomposites. Compos. Sci. Technol. 63, 2223 (2003).

    Article  CAS  Google Scholar 

  157. D.A. Castilla-Casadiego, H.V. Ramos-Avilez, S. Herrera-Posada, B. Calcagno, L. Loyo, J. Shipmon, A. Acevedo, A. Quintana, and J. Almodovar: Engineering of a stable collagen nanofibrous scaffold with tunable fiber diameter, alignment, and mechanical properties. Macromol. Mater. Eng. 301, 1064 (2016).

    Article  CAS  Google Scholar 

  158. D.A. Castilla-Casadiego, M. Maldonado, P. Sundaram, and J. Almodovar: “Green” electrospinning of a collagen/hydroxyapatite composite nanofibrous scaffold. MRS Commun. 6, 402–407 (2016).

    Article  CAS  Google Scholar 

  159. H.B. Wang, M.E. Mullins, J.M. Cregg, A. Hurtado, M. Oudega, M.T. Trombley, and R.J. Gilbert: Creation of highly aligned electrospun poly-L-lactic acid fibers for nerve regeneration applications. J. Neural Eng 6, 16001 (2009).

    Article  Google Scholar 

  160. J.M. Corey, D.Y. Lin, K.B. Mycek, Q. Chen, S. Samuel, E.L. Feldman, and D.C. Martin: Aligned electrospun nanofibers specify the direction of dorsal root ganglia neurite growth. J. Biomed. Mater. Res. A 83, 636 (2007).

    Article  Google Scholar 

  161. S. Gnavi, B.E. Fornasari, C. Tonda-Turo, G. Ciardelli, M. Zanetti, S. Geuna, and I. Perroteau: The influence of electrospun fibre size on Schwann cell behaviour and axonal outgrowth. Mater. Sci. Eng. C 48, 620 (2015).

    Article  CAS  Google Scholar 

  162. L. Yao, N. O’Brien, A. Windebank, and A. Pandit: Orienting neurite growth in electrospun fibrous neural conduits. J. Biomed. Mater. Res. B, Appl. Biomater. 90B, 483 (2009).

    Article  CAS  Google Scholar 

  163. S. Das, M. Sharma, D. Saharia, K.K. Sarma, M.G. Sarma, B.B. Borthakur, and U. Bora: Data in support of in vivo studies of silk based gold nano-composite conduits for functional peripheral nerve regeneration. Data Br. 4, 315 (2015).

    Article  Google Scholar 

  164. J.M. Zuidema, C. Provenza, T. Caliendo, S. Dutz, and R.J. Gilbert: Magnetic NGF-releasing PLLA/iron oxide nanoparticles direct extending neurites and preferentially guide neurites along aligned electrospun microfibers. ACS Chem. Neurosci. 6, 1781 (2015).

    Article  CAS  Google Scholar 

  165. L.E. Sperling, K.P. Reis, L.G. Pozzobon, C.S. Girardi, and P. Pranke: Influence of random and oriented electrospun fibrous poly(lactic-co-glycolic acid) scaffolds on neural differentiation of mouse embryonic stem cells. J. Biomed. Mater. Res. A 105, 1333 (2017).

    Article  CAS  Google Scholar 

  166. C.M.A.P. Schuh, T.J. Morton, A. Banerjee, C. Grasl, H. Schima, R. Schmidhammer, H. Redl, and D. Ruenzler: Activated Schwann cell-Like cells on aligned fibrin-poly(lactic-co-glycolic acid) structures: a novel construct for application in peripheral nerve regeneration. Cells Tissues Organs. 200, 287 (2015).

    Article  Google Scholar 

  167. A. Basu, K. Reddy, S. Doppalapudi, A.J. Domb, W. Khan, and P.L.A. Peg: Poly (lactic acid) based hydrogels. Adv. Drug Deliv. Rev. 107, 192 (2016).

    Article  CAS  Google Scholar 

  168. B.N.A. Peppas, J.Z. Hilt, A. Khademhosseini, and R. Langer: Hydrogels in biology and medicine: from molecular principles to bionanotechnology. Adv. Mater. 18, 1345 (2006).

    Article  CAS  Google Scholar 

  169. A.M. Hilderbrand, E.M. Ovadia, M.S. Rehmann, P.M. Kharkar, C. Guo, and A.M. Kloxin: Biomaterials for 4D stem cell culture. Curr. Opin. Solid State Mater. Sci. 20, 212 (2016).

    Article  CAS  Google Scholar 

  170. S.C.-Y. Lin, Y. Wang, D.F. Wertheim, and A.G.A. Coombes: Production and in vitro evaluation of macroporous, cell-encapsulating alginate fibres for nerve repair. Mater. Sci. Eng. C 73, 653 (2017).

    Article  CAS  Google Scholar 

  171. N.A. Peppas, P. Bures, W. Leobandung, and H. Ichikawa: Hydrogels in pharmaceutical formulations. Eur. J. Pharm. Biopharm. 50, 27 (2000).

    Article  CAS  Google Scholar 

  172. K.Y. Lee and D.J. Mooney: Alginate: properties and biomedical applications. Prog. Polym. Sci. 37, 106 (2012).

    Article  CAS  Google Scholar 

  173. I.P.C. Tonda-Turo, S. Gnavi, F. Ruini, G. Gambarotta, E. Gioffredi, V. Chiono, and G. Ciardelli: Development and characterization of novel agar and gelatin injectable hydrogel as filler for peripheral nerve guidance channels. Tissue Eng. Regen. Med. 11, 197 (2014).

    Article  Google Scholar 

  174. D.R. Albrecht, G.H. Underhill, T.B. Wassermann, R.L. Sah, and S.N. Bhatia: Probing the role of multicellular organization in three-dimensional microenvironments. Nat. Methods 3, 369 (2006).

    Article  CAS  Google Scholar 

  175. R.Z. Lin and H.Y. Chang: Recent advances in three-dimensional multicellular spheroid culture for biomedical research. Biotechnol. J. 3, 1172 (2008).

    Article  CAS  Google Scholar 

  176. R.S. Cargill, K.C. Dee, and S. Malcolm: An assessment of the strength of NG108-15 cell adhesion to chemically modified surfaces. Biomaterials 20, 2417 (1999).

    Article  CAS  Google Scholar 

  177. T. Korff and H.G. Augustin: Integration of endothelial cells in multicellular spheroids prevents apoptosis and induces differentiation.–PubMed–NCBI. J. Cell Biol. 143, 1341 (1998).

    Article  CAS  Google Scholar 

  178. A.N. Koppes, K.W. Keating, A.L. McGregor, R.A. Koppes, K.R. Kearns, A.M. Ziemba, C.A. McKay, J.M. Zuidema, C.J. Rivet, R.J. Gilbert, and D.M. Thompson: Robust neurite extension following exogenous electrical stimulation within single walled carbon nanotube-composite hydrogels. Acta Biomater. 39, 34 (2016).

    Article  CAS  Google Scholar 

  179. C. Cunha, S. Panseri, O. Villa, D. Silva, and F. Gelain: 3D culture of adult mouse neural stem cells within functionalized self-assembling peptide scaffolds. Int. J. Nanomed. 6, 943 (2011).

    Article  CAS  Google Scholar 

  180. K.P. Das, T.M. Freudenrich, and W.R. Mundy: Assessment of PC12 cell differentiation and neurite growth: a comparison of morphological and neurochemical measures. Neurotoxicol. Teratol. 26, 397 (2004).

    Article  CAS  Google Scholar 

  181. Y. Wu, L. Wang, B. Guo, Y. Shao, and P.X. Ma: Electroactive biodegradable polyurethane significantly enhanced Schwann cells myelin gene expression and neurotrophin secretion for peripheral nerve tissue engineering. Biomaterials 87, 18 (2016).

    Article  CAS  Google Scholar 

  182. R. Gao, W. **u, L. Zhang, R. Zang, L. Yang, C. Wang, M. Wang, M. Wang, L. Yi, Y. Tang, Y. Gao, H. Wang, J. **, W. Liu, Y. Wang, X. Wen, Y. Yu, Y. Zhang, L. Chen, J. Chen, and S. Gao: Direct induction of neural progenitor cells transiently passes through a partially reprogrammed state. Biomaterials 119, 53 (2017).

    Article  CAS  Google Scholar 

  183. K.L. Boeshore, R.C. Schreiber, S.A. Vaccariello, H.H. Sachs, R. Salazar, J. Lee, R.R. Ratan, P. Leahy, and R.E. Zigmond: Novel changes in gene expression following axotomy of a sympathetic ganglion: A microarray analysis. J. Neurobiol. 59, 216 (2004).

    Article  CAS  Google Scholar 

  184. H. Ragelle, A. Naba, B.L. Larson, F. Zhou, M. Prijić, C.A. Whittaker, A. Del Rosario, R. Langer, R.O. Hynes, and D.G. Anderson: Comprehensive proteomic characterization of stem cell-derived extracellular matrices. Biomaterials 128, 147 (2017).

    Article  CAS  Google Scholar 

  185. C.M. Dumont, P. Karande, and D.M. Thompson: Rapid assessment of migration and proliferation: a novel 3D high-throughput platform for rational and combinatorial screening of tissue-specific biomaterials. Tissue Eng. C, Methods 20, 620 (2014).

    Article  CAS  Google Scholar 

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Acknowledgments

This work was financially supported by a subaward from the Puerto Rico Idea Network of Biomedical Research Excellence (NTH NIGMS/INBRE P20 GM103475-15).

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Correspondence to Jorge Almodovar.

Abbreviations

CPH

1,6-bis (p-carboxy phenoxy) hexane

CPTEG

1,8-bis (p-carboxyphenoxy)-3,6-dioxaoctane

ADSC

Adipose-derived stem cells

AM

Additive manufacturing

BMSC

Bone marrow mesenchymal stem cells

BDNF

Brain-derive neurotrophic factor

Cams

Cell adhesion molecules

CNS

Central nervous system

CS-PLLA

Chitosan and poly lactic-based co-polymers

CNGs

Chitosan nerve guides

cryoGelMA

Cryopolymerized gelatin methacryloyl

DSP

Dibasic sodium phosphate

DMD

Digital micro-mirror arrays devices

DRGs

Dorsal root ganglia

EGR 2

Early growth response 2

ECM

Extracellular matrix

FFT

Fast Fourier transform

FDA

Food and Drug Administration

FDM

Fused deposition modeling

GelMA

Gelatin methacryloyl

A/GL_GP

Genipin

GDNF

Glial cell-derived neurotrophic factor

GPTMS

Glycodoxypropyltrimethoxysilane

GAGs

Glycosaminoglycans

GNP

Gold nanoparticles

GFs

Growth factors

GAP43

Growth-associated protein

HA4

Hyaluronan tetrasaccharide

HA

Hyaluronic acid/hyaluronan

iPSC

Induced pluripotent stem cells

LN

Laminin

LNGFR

low affinity NGF receptor

MSCs

Mesenchymal stem cells

mESCs

Mouse embryonic stem cells

MCS

Multicellular spheroids

NOBECs

Neonatal olfactory bulb ensheating Cells

NGF

Nerve growth factor

NGCs

Nerve guide conduits/nerve guide channels

NCAM

Neuronal cellular adhesion molecules

NT

Neurotrophin

NT-4/5

Neurotrophin 4/5

NT-3

Neurotrophin-3

OECs

Olfactory ensheathing cells

PNS

Peripheral nervous system

PCLA

Poly(chitosan-g-lactic acid)

PCL

Poly-e-caprolactone

PEG

Poly-ethylene glycol

PEGDA

Poly (ethylene glycol) diacrylate

PEO

Polyethylene oxide

PLGA

Poly-lactic-co-glycolic acid

PLLA

Poly-L-lactic acid

Ppy

Polypyrrole

PVA

Polyvinyl alcohol

RP

Rapid prototy**

SEM

Scanning electron microscopy

SC

Schwann cells

PMP 22

Schwann cells peripheral myelin protein 22

SCLs

Schwann-like cells

SH-EP and/or SH-SY5Y Cells

Human neuroblastoma cells

SLS

Structured light scanning

SCG

Primary superior cervical ganglion neurons

TENC

Tissue-engineered nerve conduit

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Ayala-Caminero, R., Pinzón-Herrera, L., Rivera Martinez, C.A. et al. Polymeric scaffolds for three-dimensional culture of nerve cells: a model of peripheral nerve regeneration. MRS Communications 7, 391–415 (2017). https://doi.org/10.1557/mrc.2017.90

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