Skip to main content
SpringerLink
Log in

Fundamentals and Current Strategies for Peripheral Nerve Repair and Regeneration

  • Chapter
  • First Online:
Bioinspired Biomaterials

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1249 ))

Abstract

A body of evidence indicates that peripheral nerves have an extraordinary yet limited capacity to regenerate after an injury. Peripheral nerve injuries have confounded professionals in this field, from neuroscientists to neurologists, plastic surgeons, and the scientific community. Despite all the efforts, full functional recovery is still seldom. The inadequate results attained with the “gold standard” autograft procedure still encourage a dynamic and energetic research around the world for establishing good performing tissue-engineered alternative grafts. Resourcing to nerve guidance conduits, a variety of methods have been experimentally used to bridge peripheral nerve gaps of limited size, up to 30–40 mm in length, in humans. Herein, we aim to summarize the fundamentals related to peripheral nerve anatomy and overview the challenges and scientific evidences related to peripheral nerve injury and repair mechanisms. The most relevant reports dealing with the use of both synthetic and natural-based biomaterials used in tissue engineering strategies when treatment of nerve injuries is envisioned are also discussed in depth, along with the state-of-the-art approaches in this field.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 199.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. Battiston B, Papalia I, Tos P et al (2009) Peripheral nerve repair and regeneration research: a historical note. Int Rev Neurobiol 87:1–7

    PubMed  Google Scholar 

  2. Belen D, Aciduman A, Er U (2009) History of peripheral nerve repair: may the procedure have been practiced in Hippocratic School? Surg Neurol 72(2):190–193

    PubMed  Google Scholar 

  3. Wu D, Murashov AK (2013) Molecular mechanisms of peripheral nerve regeneration: emerging roles of microRNAs. Front Physiol 4:55–55

    PubMed  PubMed Central  Google Scholar 

  4. Geuna S, Tos P, Battiston B (2012) Emerging issues in peripheral nerve repair. Neural Regen Res 7(29):2267–2272

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Zhang PX, Han N, Kou YH et al (2019) Tissue engineering for the repair of peripheral nerve injury. Neural Regen Res 14(1):51–58

    PubMed  PubMed Central  Google Scholar 

  6. Siemionow M, Bozkurt M, Zor F (2010) Regeneration and repair of peripheral nerves with different biomaterials: review. Microsurgery 30(7):574–588

    PubMed  Google Scholar 

  7. Pixley SK, Hopkins TM, Little KJ et al (2016) Evaluation of peripheral nerve regeneration through biomaterial conduits via micro-CT imaging. Laryngoscope Investig Otolaryngol 1(6):185–190

    PubMed  PubMed Central  Google Scholar 

  8. Herculano Houzel S (2012) Brain evolution. In: Paxinos G, Mai JK (eds) The human nervous system, 3rd edn. Academic Press, San Diego, pp 2–13

    Google Scholar 

  9. Balaji S, Kumar R, Sripriya R et al (2012) Preparation and comparative characterization of keratin–chitosan and keratin–gelatin composite scaffolds for tissue engineering applications. Mater Sci Eng C 32(4):975–982

    CAS  Google Scholar 

  10. Lobko PI, Ladutjko SI, Bogdanova MI et al (1979) Ganglia formation of the peripheral nervous system. Acta Anat (Basel) 103(4):395–399

    CAS  Google Scholar 

  11. Payne SL (2019) Central nervous system. In: Atala A, Lenza R, Nerem R, Thomson J (eds) Principles of regenerative medicine, 3rd edn. Academic Press, Boston, pp 1199–1221

    Google Scholar 

  12. Birch R (2013) Peripheral nerve injuries: a clinical guide. Springer, London

    Google Scholar 

  13. Fricker M, Tolkovsky AM et al (2018) Neuronal cell death. Physiol Rev 98(2):813–880

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Rotshenker S (2011) Wallerian degeneration: the innate-immune response to traumatic nerve injury. J Neuroinflammation 8:109

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Grinsell D, Keating CP (2014) Peripheral nerve reconstruction after injury: a review of clinical and experimental therapies. Biomed Res Int 13:1–14

    Google Scholar 

  16. López Cebral R, Silva Crreia J, Reis RL (2017) Peripheral nerve injury: current challenges, conventional treatment approaches, and new trends in biomaterials-based regenerative strategies. ACS Biomate Sci Eng 3(12):3098–3122

    Google Scholar 

  17. Gaudin R, Knipfer C, Henningsen A et al (2016) Approaches to peripheral nerve repair: Generations of biomaterial conduits yielding to replacing autologous nerve grafts in craniomaxillofacial surgery. Biomed Res Int 2016:1–19

    Google Scholar 

  18. Rosso G, Liashkovich I, Gess B et al (2014) Unravelling crucial biomechanical resilience of myelinated peripheral nerve fibres provided by the schwann cell basal lamina and PMP22. Sci Rep 4:7286

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Zhu S, Ge J, Wang Y et al (2014) A synthetic oxygen carrier-olfactory ensheathing cell composition system for the promotion of sciatic nerve regeneration. Biomaterials 35(5):1450–1461

    CAS  PubMed  Google Scholar 

  20. Belkas JS, Shoichet MS, Midha R (2004) Peripheral nerve regeneration through guidance tubes. Neurol Res 26(2):151–160

    PubMed  Google Scholar 

  21. Jaquet JB, Luijsterburg AJ, Kalmijn S et al (2001) Median, ulnar, and combined median-ulnar nerve injuries: functional outcome and return to productivity. J Trauma 51(4):687–692

    CAS  PubMed  Google Scholar 

  22. Kawano H, Kimura Kuroda J, Komuta Y et al (2012) Role of the lesion scar in the response to damage and repair of the central nervous system. Cell Tissue Res 349(1):169–180

    PubMed  PubMed Central  Google Scholar 

  23. Jessen KR, Mirsky R (2016) The repair schwann cell and its function in regenerating nerves. J Physiol 594(13):3521–3531

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Dahlin LB (2013) The role of timing in nerve reconstruction. In: Geuna S, Perroteau I, Tos P, Battiston B (eds) International review of neurobiology. vol 109. Academic Press, Malmö, pp 151–164

    Google Scholar 

  25. Robinson LR (2000) Traumatic injury to peripheral nerves. Muscle Nerve 23(6):863–873

    CAS  PubMed  Google Scholar 

  26. Ghasemi Rad M, Nosair E, Vegh A et al (2014) A handy review of carpal tunnel syndrome: from anatomy to diagnosis and treatment. World J Radiol 6(6):284–300

    PubMed  PubMed Central  Google Scholar 

  27. Plastaras CT, Chhatre A, Kotcharian AS (2016) Perioperative upper extremity peripheral nerve traction injuries. Orthop Clin North Am 45(1):47–53

    Google Scholar 

  28. Won JC, Park TS (2016) Recent advances in diagnostic strategies for diabetic peripheral neuropathy. Endocrinol Metab (Seoul) 31(2):230–238

    CAS  Google Scholar 

  29. Wojtkiewicz DM, Saunders J, Domeshek L et al (2015) Social impact of peripheral nerve injuries. Hand (NY) 10(2):161–167

    Google Scholar 

  30. Seddon HJ (1943) Three types of nerve injury. Brain 66(4):237–288

    Google Scholar 

  31. Sunderland S (1951) A classification of peripheral nerve injuries producing loss of function. Brain 74(4):491–516

    CAS  PubMed  Google Scholar 

  32. DeFrancesco LA, Lindborg JA, Niemi JP et al (2015) The neuroimmunology of degeneration and regeneration in the peripheral nervous system. Neuroscience 302:174–203

    Google Scholar 

  33. Kiryu Seo S, Kiyama H (2011) The nuclear events guiding successful nerve regeneration. Front Mol Neurosci 4:53

    PubMed  PubMed Central  Google Scholar 

  34. Conforti L, Gilley J, Coleman MP (2014) Wallerian degeneration: an emerging axon death pathway linking injury and disease. Nat Rev Neurosci 15(6):394–409

    CAS  PubMed  Google Scholar 

  35. Namgung U (2014) The role of schwann cell-axon interaction in peripheral nerve regeneration. Cells Tissues Organs 200(1):6–12

    CAS  PubMed  Google Scholar 

  36. Jessen KR, Mirsky R, Lloyd AC (2015) Schwann cells: development and role in nerve repair. Cold Spring Harb Perspect Biol 7(7):1–16

    CAS  Google Scholar 

  37. Chen P, Piao X, Bonaldo P (2015) Role of macrophages in wallerian degeneration and axonal regeneration after peripheral nerve injury. Acta Neuropathol 130(5):605–618

    CAS  PubMed  Google Scholar 

  38. Bearce EA, Erdogan B, Lowery LA (2015) TIPsy tour guides: how microtubule plus-end tracking proteins (+TIPs) facilitate axon guidance. Front Cell Neurosci 9:241

    PubMed  PubMed Central  Google Scholar 

  39. Steketee MB, Oboudiyat C, Richard D et al (2014) Regulation of intrinsic axon growth ability at retinal ganglion cell growth cones. Invest Ophthalmol Vis Sci 55(7):4369–4377

    PubMed  PubMed Central  Google Scholar 

  40. Fu SY, Gordon T (1997) The cellular and molecular basis of peripheral nerve regeneration. Mol Neurobiol 14(1-2):67–116

    CAS  PubMed  Google Scholar 

  41. Bhatheja K, Field J (2006) Schwann cells: origins and role in axonal maintenance and regeneration. Int J Biochem Cell Biol 38(12):1995–1999

    CAS  PubMed  Google Scholar 

  42. Jessen KR, Mirsky R (2008) Negative regulation of myelination: relevance for development, injury, and demyelinating disease. Glia 56(14):1552–1565

    PubMed  Google Scholar 

  43. Brushart TM, Aspalter M, Griffin JW et al (2013) Schwann cell phenotype is regulated by axon modality and central-peripheral location, and persists in vitro. Exp Neurol 247:272–281

    CAS  PubMed  PubMed Central  Google Scholar 

  44. McKerracher L, David S, Jackson LD et al (1994) Identification of myelin-associated glycoprotein as a major myelin-derived inhibitor of neurite growth. Neuron 13(4):805–811

    CAS  PubMed  Google Scholar 

  45. Namgung U (2015) The role of Schwann cell-axon interaction in peripheral nerve regeneration. Cells Tissues Organs 200(1):6–12

    Google Scholar 

  46. Arthur Farraj PJ, Latouche M, Wilton DK et al (2012) C-Jun reprograms schwann cells of injured nerves to generate a repair cell essential for regeneration. Neuron 75(4):633–647

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Dahlin LB (2008) Techniques of peripheral nerve repair. Scand J Surg 97(4):310–316

    CAS  PubMed  Google Scholar 

  48. Dellon ES, Dellon AL (1993) The first nerve graft, vulpian, and the nineteenth century neural regeneration controversy. J Hand Surg [Am] 18(2):369–372

    CAS  Google Scholar 

  49. Isaacs J (2010) Treatment of acute peripheral nerve injuries: current concepts. J Hand Surg [Am] 35(3):491–497

    Google Scholar 

  50. Suchyta MA, Sabbagh MD, Morsy M et al (2016) Advances in peripheral nerve regeneration as it relates to VCA. Vasc Compos Allotransplant 3(1-2):75–88

    Google Scholar 

  51. Fries CA, Tuder DW, Davis MR (2015) Preclinical models in vascularized composite allotransplantation. Curr Transpl Rep 2(3):284–289

    Google Scholar 

  52. Vale TA, Symmonds M, Polydefkis M et al (2017) Chronic non-freezing cold injury results in neuropathic pain due to a sensory neuropathy. Brain 140(10):2557–2569

    PubMed  PubMed Central  Google Scholar 

  53. Archibald SJ, Shefner J, Krarup C et al (1995) Monkey median nerve repaired by nerve graft or collagen nerve guide tube. J Neurosci 15(5 Pt 2):4109–4123

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Lovati AB, D’Arrigo D, Odella S et al (2018) Nerve repair using decellularized nerve grafts in rat models. A review of the literature. Front Cell Neurosci 12:427–427

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Gulati AK (1988) Evaluation of acellular and cellular nerve grafts in repair of rat peripheral nerve. J Neurosurg 68(1):117–123

    CAS  PubMed  Google Scholar 

  56. Freytes DO, Badylk SF, Webster TJ et al (2004) Biaxial strength of multilaminated extracellular matrix scaffolds. Biomaterials 25(12):2353–2361

    CAS  PubMed  Google Scholar 

  57. De Filippo RE, Yoo JJ, Atala A (2002) Urethral replacement using cell seeded tubularized collagen matrices. J Urol 168(4 Pt 2):1789–1792

    PubMed  Google Scholar 

  58. Woods T, Gratzer PF (2005) Effectiveness of three extraction techniques in the development of a decellularized bone-anterior cruciate ligament-bone graft. Biomaterials 26(35):7339–7349

    CAS  PubMed  Google Scholar 

  59. Gamba PG, Conconi MT, Lo Piccolo R et al (2002) Experimental abdominal wall defect repaired with acellular matrix. Pediatr Surg Int 18(5-6):327–331

    CAS  PubMed  Google Scholar 

  60. Kim BS, Yoo JJ, Atala A (2004) Peripheral nerve regeneration using acellular nerve grafts. J Biomed Mater Res A 68(2):201–209

    PubMed  Google Scholar 

  61. Lin CH, Hsia K, Ma H et al (2018) In vivo performance of decellularized vascular grafts: a review article. Int J Mol Sci 19(7):1–17

    CAS  Google Scholar 

  62. Wang EW, Zhang J, Huang JH (2015) Repairing peripheral nerve injury using tissue engineering techniques. Neural Regen Res 10(9):1393–1394

    PubMed  PubMed Central  Google Scholar 

  63. Chang W, Shah MB, Lee P et al (2018) Tissue-engineered spiral nerve guidance conduit for peripheral nerve regeneration. Acta Biomater 73:302–311

    PubMed  Google Scholar 

  64. Gonzalez Perez F, Cobianchi S, Geuna S et al (2015) Tubulization with chitosan guides for the repair of long gap peripheral nerve injury in the rat. Microsurgery 35(4):300–308

    CAS  PubMed  Google Scholar 

  65. Kehoe S, Zhang XF, Boyd D (2012) FDA approved guidance conduits and wraps for peripheral nerve injury: a review of materials and efficacy. Injury 43(5):553–572

    CAS  PubMed  Google Scholar 

  66. De Ruiter GCW, Malessy MJA, Yaszemski MJ et al (2009) Designing ideal conduits for peripheral nerve repair. Neurosurg Focus 26(2):1–9

    Google Scholar 

  67. Bueno FR, Shah SB (2008) Implications of tensile loading for the tissue engineering of nerves. Tissue Eng Part B Rev 14(3):219–233

    PubMed  Google Scholar 

  68. Gu X, Ding F, Williams DF (2014) Neural tissue engineering options for peripheral nerve regeneration. Biomaterials 35(24):6143–6156

    CAS  PubMed  Google Scholar 

  69. de Luca AC, Lacour SP et al (2014) Extracellular matrix components in peripheral nerve repair: how to affect neural cellular response and nerve regeneration? Neural Regen Res 9(22):1943–1948

    PubMed  PubMed Central  Google Scholar 

  70. Belanger K, Schlatter G, Hébraud A et al (2018) A multi-layered nerve guidance conduit design adapted to facilitate surgical implantation. Health Sci Rep 1(12):1–13

    Google Scholar 

  71. Carvalho CR, Costa JB, Da Silva MA et al (2018) Tunable enzymatically cross-linked silk fibroin tubular conduits for guided tissue regeneration. Adv Healthc Mater 7(17):1–17

    Google Scholar 

  72. Menorca RMG, Fussell TS, Elfar JC (2013) Peripheral nerve trauma: mechanisms of injury and recovery. Hand Clin 29(3):317–330

    PubMed  PubMed Central  Google Scholar 

  73. Subramanian A, Krishnan UM, Sethuraman S (2009) Development of biomaterial scaffold for nerve tissue engineering: biomaterial mediated neural regeneration. J Biomed Sci 16(1):108–108

    PubMed  PubMed Central  Google Scholar 

  74. Chen YS, Chang JY, Cheng CY et al (2005) An in vivo evaluation of a biodegradable genipin-cross-linked gelatin peripheral nerve guide conduit material. Biomaterials 26(18):3911–3918

    CAS  PubMed  Google Scholar 

  75. Yang Y, Zhao Y, Gu Y et al (2009) Degradation behaviors of nerve guidance conduits made up of silk fibroin in vitro and in vivo. Polym Degrad Stab 94(12):2213–2220

    CAS  Google Scholar 

  76. Wang ML, Rivlin M, Graham JG et al (2019) Peripheral nerve injury, scarring, and recovery. Connect Tissue Res 60(1):3–9

    PubMed  Google Scholar 

  77. Huang C, Ouyang Y, Niu H et al (2015) Nerve guidance conduits from aligned nanofibers: improvement of nerve regeneration through longitudinal nanogrooves on a fiber Surface. ACS Appl Mater Interfaces 7(13):7189–7196

    CAS  PubMed  Google Scholar 

  78. Liu C, Wang C, Zhao Q et al (2018) Incorporation and release of dual growth factors for nerve tissue engineering using nanofibrous bicomponent scaffolds. Biomed Mater 13(4):1–18

    Google Scholar 

  79. Cattin AL, Burden JJ, Van Emmenis L et al (2015) Macrophage-induced blood vessels guide schwann cell-mediated regeneration of peripheral nerves. Cell 162(5):1127–1139

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Zhao YH, Niu CM, Shi JQ et al (2018) Novel conductive polypyrrole/silk fibroin scaffold for neural tissue repair. Neural Regen Res 13(8):1455–1464

    PubMed  PubMed Central  Google Scholar 

  81. Muangsanit P, Shipley RJ, Phillips JB (2018) Vascularization strategies for peripheral nerve tissue engineering. Anat Rec (Hoboken) 301(10):1657–1667

    Google Scholar 

  82. Giannessi E, Coli A, Stornelli MR et al (2014) An autologously generated platelet-rich plasma suturable membrane may enhance peripheral nerve regeneration after neurorraphy in an acute injury model of sciatic nerve neurotmesis. J Reconstr Microsurg 30(9):617–626

    PubMed  Google Scholar 

  83. Stang F, Keilhoff G, Fansa H (2009) Biocompatibility of different nerve tubes. Materials (Basel) 2(4):1480

    CAS  Google Scholar 

  84. Muheremu A, Ao Q (2015) Past, present, and future of nerve conduits in the treatment of peripheral nerve injury. Biomed Res Int 2015:1–7

    Google Scholar 

  85. Nardo T, Irene C, Ruini F et al (2017) Synthetic biomaterial for regenerative medicine applications. In: Orlando G, Remzzi G, Williams DF (eds) Kidney transplantation, bioengineering and regeneration, 1st edn. Academic Press, Turin, pp 901–921

    Google Scholar 

  86. Matsumine H, Sasaki R, Yamato M et al (2014) A polylactic acid non-woven nerve conduit for facial nerve regeneration in rats. J Tissue Eng Regen Med 8(6):454–462

    CAS  PubMed  Google Scholar 

  87. Lu MC, Huang YT, Lin JH et al (2009) Evaluation of a multi-layer microbraided polylactic acid fiber-reinforced conduit for peripheral nerve regeneration. J Mater Sci Mater Med 20(5):1175–1180

    CAS  PubMed  Google Scholar 

  88. Zeng CG, Xiong Y, Quan D et al (2014) Fabrication and evaluation of PLLA multichannel conduits with nanofibrous microstructure for the differentiation of NSCs in vitro. Tissue Eng Part A 20(5–6):1038–1048

    CAS  PubMed  PubMed Central  Google Scholar 

  89. Rutkowski GE, Miller CA, Jeftinija S et al (2004) Synergistic effects of micropatterned biodegradable conduits and Schwann cells on sciatic nerve regeneration. J Neural Eng 1(3):151–157

    PubMed  Google Scholar 

  90. Shin RH, Friedrich PF, Crum BA et al (2009) Treatment of a segmental nerve defect in the rat with use of bioabsorbable synthetic nerve conduits: a comparison of commercially available conduits. J Bone Joint Surg Am 91(9):2194–2204

    PubMed  Google Scholar 

  91. Navissano M, Malan F, Carnino R et al (2005) Neurotube® for facial nerve repair. Microsurgery 25(4):268–271

    PubMed  Google Scholar 

  92. Wu T, Li D, Wang Y et al (2017) Laminin-coated nerve guidance conduits based on poly(l-lactide-co-glycolide) fibers and yarns for promoting Schwann cells’ proliferation and migration. J Mater Chem B 5(17):3186–3194

    CAS  PubMed  Google Scholar 

  93. Labroo P, Shea J, Edwards K et al (2017) Novel drug delivering conduit for peripheral nerve regeneration. J Neural Eng 14(6):066011

    PubMed  Google Scholar 

  94. Lee SJ, Nowicki M, Harris B et al (2017) Fabrication of a highly aligned neural scaffold via a table top stereolithography 3D printing and electrospinning. Tissue Eng Part A 23(11-12):491–502

    PubMed  Google Scholar 

  95. Kokai LE, Ghaznavi AM, Marra KG (2010) Incorporation of double-walled microspheres into polymer nerve guides for the sustained delivery of glial cell line-derived neurotrophic factor. Biomaterials 31(8):2313–2322

    CAS  PubMed  Google Scholar 

  96. Hsu S, Chang WC, Yen CT (2017) Novel flexible nerve conduits made of water-based biodegradable polyurethane for peripheral nerve regeneration. J Biomed Mater Res Part A 105(5):1383–1392

    CAS  Google Scholar 

  97. Singh A, Shiekh PA, Das M et al (2018) Aligned chitosan-gelatin cryogel-filled polyurethane nerve guidance channel for neural tissue engineering: fabrication, characterization, and in vitro evaluation. Biomacromolecules 20(2):662–673

    PubMed  Google Scholar 

  98. Stocco E, Barbon S, Lora L et al (2018) Partially oxidized polyvinyl alcohol conduit for peripheral nerve regeneration. Sci Rep 8(1):604–604

    PubMed  PubMed Central  Google Scholar 

  99. Wan H, Li DZ, Yang F et al (2007) Research about schwann cells and PLGA implanted to rat transected spinal cord. Zhonghua Wai Ke Za Zhi 45(12):843–846

    PubMed  Google Scholar 

  100. Peng SW, Li CW, Wang GJ et al (2017) Nerve guidance conduit with a hybrid structure of a PLGA microfibrous bundle wrapped in a micro/nanostructured membrane. Int J Nanomedicine 12:421–432

    CAS  PubMed  PubMed Central  Google Scholar 

  101. Liu H, Lv P, Zhu Y et al (2017) Salidroside promotes peripheral nerve regeneration based on tissue engineering strategy using Schwann cells and PLGA: in vitro and in vivo. Sci Rep 7:1–11

    Google Scholar 

  102. Xu F, Zhang K, Lv P et al (2017) NECL1 coated PLGA as favorable conduits for repair of injured peripheral nerve. Mater Sci Eng C 70:1132–1140

    CAS  Google Scholar 

  103. Tanir TE, Kiziltay A, Malikmammadov E et al (2018) PCL and PCL-based materials in biomedical applications. J Biomater Sci Polym Ed 29(7-9):863–893

    PubMed  Google Scholar 

  104. Wang W, Huang B, Byun JJ et al (2019) Assessment of PCL/carbon material scaffolds for bone regeneration. J Mech Behav Biomed Mater 93:52–60

    CAS  PubMed  Google Scholar 

  105. Fu N, Liao J, Lin S et al (2016) PCL-PEG-PCL film promotes cartilage regeneration in vivo. Cell Prolif 49(6):729–739

    CAS  PubMed  PubMed Central  Google Scholar 

  106. Bala Balakrishnan P, Gardella L, Forouharshad M et al (2018) Star poly(ε-caprolactone)-based electrospun fibers as biocompatible scaffold for doxorubicin with prolonged drug release activity. Colloids Surf B: Biointerfaces 161:488–496

    PubMed  Google Scholar 

  107. Grossen P, Witzigmann D, Sieber S et al (2017) PEG-PCL-based nanomedicines: a biodegradable drug delivery system and its application. J Control Release 260:46–60

    CAS  PubMed  Google Scholar 

  108. Pathak VM, Navneet (2017) Review on the current status of polymer degradation: a microbial approach. Bioresour Bioprocess 4(1):15

    Google Scholar 

  109. Salmoria GV, Paggi RA, Castro F et al (2016) Development of PCL/Ibuprofen tubes for peripheral nerve regeneration. Procedia CIRP 49:193–198

    Google Scholar 

  110. Mobasseri A, Faroni A, Minogue BM et al (2015) Polymer scaffolds with preferential parallel grooves enhance nerve regeneration. Tissue Eng Part A 21(5-6):1152–1162

    CAS  PubMed  PubMed Central  Google Scholar 

  111. Zhang XF, Coughlan A, O’Shea H et al (2012) Experimental composite guidance conduits for peripheral nerve repair: an evaluation of ion release. Mater Sci Eng C 32(6):1654–1663

    CAS  Google Scholar 

  112. Wei J, Ao Q, Huang L et al (2018) Constructing conductive conduit with conductive fibrous infilling for peripheral nerve regeneration. Chem Eng J 345:566–577

    Google Scholar 

  113. Sun B, Zhou Z, Li D et al (2019) Polypyrrole-coated poly(l-lactic acid-co-ε-caprolactone)/silk fibroin nanofibrous nerve guidance conduit induced nerve regeneration in rat. Mater Sci Eng C Mater Biol Appl 94:190–199

    CAS  PubMed  Google Scholar 

  114. Du J, Chen H, Qing L et al (2018) Biomimetic neural scaffolds: a crucial step towards optimal peripheral nerve regeneration. Biomater Sci 6(6):1299–1311

    CAS  PubMed  PubMed Central  Google Scholar 

  115. Pfister LA, Papaloïzos M, Merkle HP et al (2007) Hydrogel nerve conduits produced from alginate/chitosan complexes. J Biomed Mater Res A 80A(4):932–937

    CAS  Google Scholar 

  116. Wang ZZ, Sakiyama Elbert SE (2018) Matrices, scaffolds & carriers for cell delivery in nerve regeneration. Exp Neurol 319:1–17

    Google Scholar 

  117. Resch A, Wolf S, Radtke C et al (2018) Co-culturing human adipose derived stem cells and schwann cells on spider silk-a new approach as prerequisite for enhanced nerve regeneration. Int J Mol Sci 20(1):71

    PubMed Central  Google Scholar 

  118. Wang C, Jia Y, Yang W et al (2018) Silk fibroin enhances peripheral nerve regeneration by improving vascularization within nerve conduits. J Biomed Mater Res A 106(7):2070–2077

    CAS  PubMed  Google Scholar 

  119. Yang Y, Ding F, Wu J et al (2007) Development and evaluation of silk fibroin-based nerve grafts used for peripheral nerve regeneration. Biomaterials 28(36):5526–5535

    CAS  PubMed  Google Scholar 

  120. Das S, Sharma M, Saharia D et al (2015) In vivo studies of silk based gold nano-composite conduits for functional peripheral nerve regeneration. Biomaterials 62:66–75

    CAS  PubMed  Google Scholar 

  121. Sierpinski P, Garrett J, Ma J et al (2008) The use of keratin biomaterials derived from human hair for the promotion of rapid regeneration of peripheral nerves. Biomaterials 29(1):118–128

    CAS  PubMed  Google Scholar 

  122. Pace LA, Plate JF, Mannava S et al (2014) A human hair keratin hydrogel scaffold enhances median nerve regeneration in nonhuman primates: An electrophysiological and histological study. Tissue Eng Part A 20(3-4):507–517

    CAS  PubMed  Google Scholar 

  123. Lin YC, Ramadan M, Van Dyke M et al (2012) Keratin gel filler for peripheral nerve repair in a rodent sciatic nerve injury model. Plast Reconstr Surg 129(1):67–78

    CAS  PubMed  Google Scholar 

  124. Meyer C, Stenberg L, Gonzalez Perez F et al (2016) Chitosan-film enhanced chitosan nerve guides for long-distance regeneration of peripheral nerves. Biomaterials 76:33–51

    CAS  PubMed  Google Scholar 

  125. Moattari M, Kouchesfehani HM, Kaka G et al (2018) Chitosan-film associated with mesenchymal stem cells enhanced regeneration of peripheral nerves: a rat sciatic nerve model. J Chem Neuroanat 88:46–54

    CAS  PubMed  Google Scholar 

  126. Carvalho CR, Silva Correia J, Silva JM et al (2017) Investigation of cell adhesion in chitosan membranes for peripheral nerve regeneration. Mater Sci Eng C Mater Biol Appl 71:1122–1134

    CAS  PubMed  Google Scholar 

  127. Lin SC, Wang Y, Wertheim DF et al (2017) Production and in vitro evaluation of macroporous, cell-encapsulating alginate fibres for nerve repair. Mater Sci Eng C Mater Biol Appl 73:653–664

    CAS  PubMed  Google Scholar 

  128. Sarker MD, Naghieh S, Ning L et al (2019) Bio-fabrication of peptide-modified alginate scaffolds: printability, mechanical stability and neurite outgrowth assessments. Bioprinting 2019:1–19

    Google Scholar 

  129. Mondal M, Trivedy K, Nirmal Kumar S (2007) The silk proteins, sericin and fibroin in silkworm, Bombyx mori Linn., – a review. Caspian J Env Sci 5(2):63–76

    Google Scholar 

  130. Jastrzebska K, Kucharczky K, Dams Kozlowska H et al (2015) Silk as an innovative biomaterial for cancer therapy. Rep Pract Oncol Radiother 20(2):87–98

    PubMed  Google Scholar 

  131. Vepari C, Kaplan DL (2007) Silk as a biomaterial. Prog Polym Sci 32(8-9):991–1007

    CAS  PubMed  PubMed Central  Google Scholar 

  132. Costa JB, Silva Correia J, Oliveira JM et al (2017) Fast setting silk fibroin bioink for bioprinting of patient-specific memory-shape implants. Adv Healthc Mater 6(22):1701021

    Google Scholar 

  133. Ribeiro VP, Sliva Correia J, Goncalves C et al (2018) Rapidly responsive silk fibroin hydrogels as an artificial matrix for the programmed tumor cells death. PLoS One 13(4):1–21

    Google Scholar 

  134. Carvalho MR, Maia FR, Reis RL et al (2018) Tuning enzymatically crosslinked silk fibroin hydrogel properties for the development of a colorectal cancer extravasation 3D model on a chip. Global Chall 2(5-6):1–10

    Google Scholar 

  135. Dinis TM, Elia R, Vidal G et al (2015) 3D multi-channel bi-functionalized silk electrospun conduits for peripheral nerve regeneration. J Mech Behav Biomed Mater 41:43–55

    CAS  PubMed  Google Scholar 

  136. Ng K (2016) Human hair keratin templates for biomedical applications. Front Bioeng Biotechnol. Conference Abstract: 10th World Biomaterials Congress. https://doi.org/10.3389/conf.FBIOE.2016.01.01729

  137. Ko J, Nguyen LTH, Surendran A et al (2017) Human hair keratin for biocompatible flexible and transient electronic devices. ACS Appl Mater Interfaces 9(49):43004–43012

    CAS  PubMed  Google Scholar 

  138. Kan Y, Yanhui L, Batzaya B et al (2018) Visible light crosslinkable human hair keratin hydrogels. Bioeng Transl Med 3(1):37–48

    Google Scholar 

  139. Lee HN, Noh KT, Lee SC et al (2014) Human hair keratin and its-based biomaterials for biomedical applications. Tissue Eng Regen Med 11(4):255–265

    CAS  Google Scholar 

  140. Apel PJ, Garrett JP, Sierpinski P et al (2008) Peripheral nerve regeneration using a keratin-based scaffold: long-term functional and histological outcomes in a mouse model. J Hand Surg [Am] 33(9):1541–1547

    Google Scholar 

  141. Bak M, Gutkowska ON, Wagner E et al (2017) The role of chitin and chitosan in peripheral nerve reconstruction. Polim Med 47(1):43–47

    PubMed  Google Scholar 

  142. Muzzarelli RAA (1977) Chitin. Pergamon press, New York, pp 5–44

    Google Scholar 

  143. Marguerite R (2006) Chitin and chitosan: properties and applications. Prog Polym Sci 31(7):603–632

    Google Scholar 

  144. Freier T, Montenegro R, Shan KH et al (2005) Chitin-based tubes for tissue engineering in the nervous system. Biomaterials 26(22):4624–4632

    CAS  PubMed  Google Scholar 

  145. Martin LE, Nieto DM, Nieto SM (2012) Differential adhesiveness and neurite-promoting activity for neural cells of chitosan, gelatin, and poly-L-lysine films. J Biomater Appl 26(7):791–809

    Google Scholar 

  146. Wenling C, Duohui J, Jiamou L et al (2005) Effects of the degree of deacetylation on the physicochemical properties and Schwann cell affinity of chitosan films. J Biomater Appl 20(2):157–177

    PubMed  Google Scholar 

  147. Wrobel S, Serra SC, Ribeiro SS et al (2014) In vitro evaluation of cell-seeded chitosan films for peripheral nerve tissue engineering. Tissue Eng Part A 20(17-18):2339–2349

    CAS  PubMed  PubMed Central  Google Scholar 

  148. Ashleigh C, Narayan B, Minqin Z (2011) Fabrication and cellular compatibility of aligned chitosan–PCL fibers for nerve tissue regeneration. Carbohydr Polym 85(1):149–156

    Google Scholar 

  149. Gnavi S, Fornasari BE, Tonda TC et al (2018) In vitro evaluation of gelatin and chitosan electrospun fibres as an artificial guide in peripheral nerve repair: a comparative study. J Tissue Eng Regen Med 12(2):e679–e694

    CAS  PubMed  Google Scholar 

  150. Wang W, Itoh S, Konno K et al (2009) Effects of Schwann cell alignment along the oriented electrospun chitosan nanofibers on nerve regeneration. J Biomed Mater Res A 91(4):994–1005

    PubMed  Google Scholar 

  151. Haastert TK, Geuna S, Dahlin LB et al (2013) Chitosan tubes of varying degrees of acetylation for bridging peripheral nerve defects. Biomaterials 34(38):9886–9904

    Google Scholar 

  152. Stenberg L, Kodama A, Lindwall BC et al (2016) Nerve regeneration in chitosan conduits and in autologous nerve grafts in healthy and in type 2 diabetic Goto-Kakizaki rats. Eur J Neurosci 43(3):463–473

    PubMed  Google Scholar 

  153. Lee KY, Mooney DJ (2012) Alginate: properties and biomedical applications. Prog Polym Sci 37(1):106–126

    CAS  PubMed  PubMed Central  Google Scholar 

  154. Suzuki Y, Tanihara M, Nishimura Y et al (1999) In vivo evaluation of a novel alginate dressing. J Biomed Mater Res 48(4):522–527

    CAS  PubMed  Google Scholar 

  155. Ochbaum G, Davidovich PM, Bitton R (2018) Tuning the mechanical properties of alginate–peptide hydrogels. Soft Matter 14(21):4364–4373

    CAS  PubMed  Google Scholar 

  156. Suzuki Y, Tanihara M, Ohnishi K et al (1999) Cat peripheral nerve regeneration across 50 mm gap repaired with a novel nerve guide composed of freeze-dried alginate gel. Neurosci Lett 259(2):75–78

    CAS  PubMed  Google Scholar 

  157. Hashimoto T, Suzuki Y, Kitada M et al (2002) Peripheral nerve regeneration through alginate gel: analysis of early outgrowth and late increase in diameter of regenerating axons. Exp Brain Res 146(3):356–368

    CAS  PubMed  Google Scholar 

  158. Quigley AF, Bulluss KJ, Kyratzis IL et al (2013) Engineering a multimodal nerve conduit for repair of injured peripheral nerve. J Neural Eng 10(1):016008

    CAS  PubMed  Google Scholar 

  159. Naghieh S, Sarker MD, Abelseth E et al (2019) Indirect 3D bioprinting and characterization of alginate scaffolds for potential nerve tissue engineering applications. J Mech Behav Biomed Mater 93:183–193

    CAS  PubMed  Google Scholar 

  160. Wu H, Liu J, Fang Q et al (2017) Establishment of nerve growth factor gradients on aligned chitosan-polylactide/alginate fibers for neural tissue engineering applications. Colloids Surf B: Biointerfaces 160:598–609

    CAS  PubMed  Google Scholar 

  161. de Luca AC, Lacour SP, Raffoul W et al (2014) Extracellular matrix components in peripheral nerve repair: how to affect neural cellular response and nerve regeneration? Neural Regen Res 9(22):1943–1948

    PubMed  PubMed Central  Google Scholar 

  162. Silvan K, Lukas P, Jody V et al (2016) Differential effects of coating materials on viability and migration of schwann cells. Materials (Basel) 9(3):150

    Google Scholar 

  163. Fujimaki H, Uchida K, Inoue G et al (2017) Oriented collagen tubes combined with basic fibroblast growth factor promote peripheral nerve regeneration in a 15 mm sciatic nerve defect rat model. J Biomed Mater Res A 105(1):8–14

    CAS  PubMed  Google Scholar 

  164. Huang L, Zhu L, Shi X et al (2018) A compound scaffold with uniform longitudinally oriented guidance cues and a porous sheath promotes peripheral nerve regeneration in vivo. Acta Biomater 68:223–236

    CAS  PubMed  Google Scholar 

  165. Bhandari PS (2013) Use of fibrin glue in the repair of brachial plexus and peripheral nerve injuries. Indian J Neurotrauma 10(1):30–32

    Google Scholar 

  166. Reichenberger MA, Mueller W, Hartmann J et al (2016) ADSCs in a fibrin matrix enhance nerve regeneration after epineural suturing in a rat model. Microsurgery 36(6):491–500

    PubMed  Google Scholar 

  167. Du J, Liu J, Yao S et al (2017) Prompt peripheral nerve regeneration induced by a hierarchically aligned fibrin nanofiber hydrogel. Acta Biomater 55:296–309

    CAS  PubMed  Google Scholar 

  168. Mosahebi A, Wiberg M, Terenghi G (2003) Addition of fibronectin to alginate matrix improves peripheral nerve regeneration in tissue-engineered conduits. Tissue Eng 9(2):209–218

    CAS  PubMed  Google Scholar 

  169. Gonzalez Perez F, Cobianchi S, Heimann C et al (2017) Stabilization, rolling, and addition of other extracellular matrix proteins to collagen hydrogels improve regeneration in chitosan guides for long peripheral nerve gaps in rats. Neurosurgery 80(3):465–474

    PubMed  Google Scholar 

  170. Kijeńska E, Prabhakaran MP, Swieszkowski W et al (2014) Interaction of Schwann cells with laminin encapsulated PLCL core–shell nanofibers for nerve tissue engineering. Eur Polym J 50:30–38

    Google Scholar 

  171. Haggerty AE, Bening MR, Pherribi G et al (2019) Laminin polymer treatment accelerates repair of the crushed peripheral nerve in adult rats. Acta Biomater 86:185–193

    CAS  PubMed  PubMed Central  Google Scholar 

  172. Entekhabi E, Haghbin NM, Sadeghi A et al (2016) Design and manufacture of neural tissue engineering scaffolds using hyaluronic acid and polycaprolactone nanofibers with controlled porosity. Mater Sci Eng C 69:380–387

    CAS  Google Scholar 

  173. Vilariño Feltrer G, Martínez Ramos C, Monleón de la Fuente A et al (2016) Schwann-cell cylinders grown inside hyaluronic-acid tubular scaffolds with gradient porosity. Acta Biomater 30:199–211

    PubMed  Google Scholar 

  174. Khan R, Khan MH (2013) Use of collagen as a biomaterial: an update. J Indian Soc Periodontol 17(4):539–542

    PubMed  PubMed Central  Google Scholar 

  175. Tiago HS, Joana MS, Ana LPM et al (2014) Marine origin collagens and its potential applications. Mar Drugs 12(12):5881–5901

    Google Scholar 

  176. Chanjuan D, Lv Y (2016) Application of collagen scaffold in tissue engineering: recent advances and new perspectives. Polymers 8(2):42

    Google Scholar 

  177. Bozkurt A, Claeys KG, Schrading S et al (2017) Clinical and biometrical 12-month follow-up in patients after reconstruction of the sural nerve biopsy defect by the collagen-based nerve guide Neuromaix. Eur J Med Res 22(1):34

    PubMed  PubMed Central  Google Scholar 

  178. Litvinov RI, Weisel JW (2016) What is the biological and clinical relevance of fibrin? Semin Thromb Hemost 42(4):333–343

    CAS  PubMed  PubMed Central  Google Scholar 

  179. Esposito F, Angileri FF, Kruse P et al (2016) Fibrin sealants in dura sealing: a systematic literature review. PLoS One 11(4):e0151533

    PubMed  PubMed Central  Google Scholar 

  180. Olcucuoglu E, Kulacoglu H, Ensari CO et al (2011) Fibrin sealant effects on the ilioinguinal nerve. J Investig Surg 24(6):267–272

    Google Scholar 

  181. Pankov R, Yamada KM (2002) Fibronectin at a glance. J Cell Sci 115(20):3861–3863

    CAS  PubMed  Google Scholar 

  182. Whitworth IH, Brown RA, Doré C et al (1995) Orientated mats of fibronectin as a conduit material for use in peripheral nerve repair. J Hand Surg (Br) 20(4):429–436

    CAS  Google Scholar 

  183. Chen YS, Hsieh CL, Tsai CC et al (2000) Peripheral nerve regeneration using silicone rubber chambers filled with collagen, laminin and fibronectin. Biomaterials 21(15):1541–1547

    CAS  PubMed  Google Scholar 

  184. Liang S, Crutcher KA (1992) Neuronal migration on laminin in vitro. Brain Res Dev Brain Res 66(1):127–132

    CAS  PubMed  Google Scholar 

  185. Adams DN, Kao EY, Hypolite CL et al (2005) Growth cones turn and migrate up an immobilized gradient of the laminin IKVAV peptide. J Neurobiol 62(1):134–147

    CAS  PubMed  Google Scholar 

  186. Zhang XF, Liu HX, Ortiz LS et al (2018) Laminin-modified and aligned poly(3-hydroxybutyrate-co-3-hydroxyvalerate)/polyethylene oxide nanofibrous nerve conduits promote peripheral nerve regeneration. J Tissue Eng Regen Med 12(1):e627–e636

    CAS  PubMed  Google Scholar 

  187. Swindle-Reilly KE, Papke JB, Kutosky HP et al (2012) The impact of laminin on 3D neurite extension in collagen gels. J Neural Eng 9(4):046007

    PubMed  Google Scholar 

  188. Zamboni F, Vieira S, Reis RL et al (2018) The potential of hyaluronic acid in immunoprotection and immunomodulation: chemistry, processing and function. Prog Mater Sci 97:97–122

    CAS  Google Scholar 

  189. Chircov C, Grumezescu AM, Bejenaru LE (2018) Hyaluronic acid-based scaffolds for tissue engineering. Romanian J Morphol Embryol 59(1):71–76

    Google Scholar 

  190. Huang L, Wang Y, Liu H et al (2017) Local injection of high-molecular hyaluronan promotes wound healing in old rats by increasing angiogenesis. Oncotarget 9(9):8241–8252

    PubMed  PubMed Central  Google Scholar 

  191. Wang KK, Nemeth IR, Seckel BR et al (1998) Hyaluronic acid enhances peripheral nerve regeneration in vivo. Microsurgery 18(4):270–275

    CAS  PubMed  Google Scholar 

  192. Ikeda K, Yamauchi D, Osamura N et al (2003) Hyaluronic acid prevents peripheral nerve adhesion. Br J Plast Surg 56(4):342–347

    CAS  PubMed  Google Scholar 

  193. Murphy SV, Atala A (2014) 3D bioprinting of tissues and organs. Nat Biotechnol 32(8):773–785

    CAS  Google Scholar 

  194. Hamburg MA, Collins FS (2010) The path to personalized medicine. N Engl J Med 363(4):301–304

    CAS  PubMed  Google Scholar 

  195. Rengier F, Mehndiratta A, von Tengg KH et al (2010) 3D printing based on imaging data: review of medical applications. Int J Comput Assist Radiol Surg 5(4):335–341

    CAS  PubMed  Google Scholar 

  196. Schmidt CE, Leach JB (2003) Neural tissue engineering: strategies for repair and regeneration. Annu Rev Biomed Eng 5:293–347

    CAS  PubMed  Google Scholar 

  197. Ji XM, Wang SS, Cai XD et al (2019) Novel miRNA, miR-sc14, promotes Schwann cell proliferation and migration. Neural Regen Res 14(9):1651–1656

    PubMed  PubMed Central  Google Scholar 

  198. Petcu EB, Midha R, McColl E et al (2018) 3D printing strategies for peripheral nerve regeneration. Biofabrication 10(3):032001

    PubMed  Google Scholar 

  199. Johnson BN, Lancaster KZ, Zhen G et al (2015) 3D printed anatomical nerve regeneration pathways. Adv Funct Mater 25(39):6205–6217

    CAS  PubMed  PubMed Central  Google Scholar 

  200. Hu Y, Wu Y, Gou Z et al (2016) 3D-engineering of cellularized conduits for peripheral nerve regeneration. Sci Rep 6:32184

    CAS  PubMed  PubMed Central  Google Scholar 

  201. Tao J, Zhang J, Du T et al (2019) Rapid 3D printing of functional nanoparticle-enhanced conduits for effective nerve repair. Acta Biomater 90:49–59

    CAS  PubMed  Google Scholar 

  202. Zhong Y, Wang L, Dong J et al (2015) Three-dimensional reconstruction of peripheral nerve internal fascicular groups. Sci Rep 5:17168

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

This work was supported by Cristiana Carvalho PhD scholarship (Norte-08-5369-FSE-000037). J. M. Oliveira also thanks the FCT for the funds provided under the program Investigador FCT 2015 (IF/01285/2015). The authors are also thankful to the FCT-funded project NanoOptoNerv (ref. PTDC/NAN-MAT/29936/2017). The authors would also like to acknowledge the project “Nano-accelerated nerve regeneration and optogenetic empowering of neuromuscular functionality” (ref. PTDC/NAN-MAT/29936/2017).

Author information

Authors and Affiliations

  1. 3B’s Research Group, I3Bs – Research Institute on Biomaterials, Biodegradables and Biomimetics, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, University of Minho, Guimarães, Portugal

    Cristiana R. Carvalho, Rui L. Reis & Joaquim M. Oliveira

  2. ICVS/3B’s – PT Government Associated Laboratory, Guimarães, Portugal

    Cristiana R. Carvalho, Rui L. Reis & Joaquim M. Oliveira

  3. The Discoveries Centre for Regenerative and Precision Medicine, Headquarters at University of Minho, Guimarães, Portugal

    Cristiana R. Carvalho, Rui L. Reis & Joaquim M. Oliveira

Authors
  1. Cristiana R. Carvalho
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rui L. Reis
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Joaquim M. Oliveira
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Joaquim M. Oliveira .

Editor information

Editors and Affiliations

  1. Institute of Cell & Tissue Engineering and College of Medicine, Catholic University of Korea, Seoul, Korea (Republic of)

    Heung Jae Chun

  2. 3B’s Research Group, I3Bs – Research Institute on Biomaterials, Biodegradables and Biomimetics, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, University of Minho, Guimarães, Portugal

    Rui L. Reis

  3. Department of Industrial Engineering and BIOtech Research Center, University of Trento, Trento, Italy

    Antonella Motta

  4. Department of BIN Convergence Technology, Department of Polymer Nano Science & Technology and Polymer BIN Research Center, Jeonbuk National University, Jeonju, Korea (Republic of)

    Gilson Khang

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Carvalho, C.R., Reis, R.L., Oliveira, J.M. (2020). Fundamentals and Current Strategies for Peripheral Nerve Repair and Regeneration. In: Chun, H.J., Reis, R.L., Motta, A., Khang, G. (eds) Bioinspired Biomaterials. Advances in Experimental Medicine and Biology, vol 1249 . Springer, Singapore. https://doi.org/10.1007/978-981-15-3258-0_12

Download citation

Publish with us

Policies and ethics

Search

Navigation