Skip to main content
SpringerLink
Log in

Current Trends and Future Perspectives for Peripheral Nerve Regeneration

  • Chapter
  • First Online:
Regenerative Medicine and Plastic Surgery

Abstract

Peripheral nerve injury may result in severe disability with substantial social and personal cost, and a potentially devastating impact to patients’ quality of life. Advances in peripheral nerve surgery, regeneration, and rehabilitation; better understanding of the pathophysiology and molecular basis of nerve injury; and refined microsurgical techniques have contributed to accelerated nerve regeneration and improved outcome for the patients. Experimental research has evolved the process of regeneration using pharmacological agents, bioengineering of sophisticated nerve conduits, pluripotent stem cells, and gene therapy. This chapter attempts a brief overview of the basic principles of nerve repair, current concepts, and future perspectives of peripheral nerve regeneration.

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 109.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
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

References

  1. Kelsey JL. Upper extremity disorders: frequency, impact, and cost. New York: Churchill Livingstone; 1997.

    Google Scholar 

  2. Kouyoumdjian JA. Peripheral nerve injuries: a retrospective survey of 456 cases. Muscle Nerve. 2006;34(6):785–8.

    Article  PubMed  Google Scholar 

  3. Siemionow M, Brzezicki G. Current techniques and concepts in peripheral nerve repair. Int Rev Neurobiol. 2009;87:141–72.

    Article  CAS  PubMed  Google Scholar 

  4. Noble J, Munro CA, Prasad VS, Midha R. Analysis of upper and lower extremity peripheral nerve injuries in a population of patients with multiple injuries. J Trauma. 1998;45(1):116–22.

    Article  CAS  PubMed  Google Scholar 

  5. Maricevic A, Erceg M. War injuries to the extremities. Mil Med. 1997;162(12):808–11.

    Article  CAS  PubMed  Google Scholar 

  6. Razaq S, Yasmeen R, Butt AW, Akhtar N, Mansoor SN. The pattern of peripheral nerve injuries among Pakistani soldiers in the war against terror. J Coll Physicians Surg Pak. 2015;25(5):363–6.

    PubMed  Google Scholar 

  7. Birch R, Misra P, Stewart MP, Eardley WG, Ramasamy A, Brown K, Shenoy R, Anand P, Clasper J, Dunn R, Etherington J. Nerve injuries sustained during warfare: Part I—Epidemiology. J Bone Joint Surg Br. 2012;94(4):523–8.

    Article  CAS  PubMed  Google Scholar 

  8. Ray WZ, Mackinnon SE. Management of nerve gaps: autografts, allografts, nerve transfers, and end-to-side neurorrhaphy. Exp Neurol. 2010;223(1):77–85.

    Article  PubMed  Google Scholar 

  9. Griffin JW, Hogan MV, Chhabra AB, Deal DN. Peripheral nerve repair and reconstruction. J Bone Joint Surg Am. 2013;95(23):2144–51.

    Article  PubMed  Google Scholar 

  10. Kline DG. Nerve surgery as it is now and as it may be. Neurosurgery. 2000;46(6):1285–93.

    Article  CAS  PubMed  Google Scholar 

  11. Tos P, Ronchi G, Papalia I, Sallen V, Legagneux J, Geuna S, Giacobini-Robecchi MG. Methods and protocols in peripheral nerve regeneration experimental research: Part I—Experimental models. Int Rev Neurobiol. 2009;87:47–79.

    Article  PubMed  Google Scholar 

  12. Costa LM, Simoes MJ, Mauricio AC, Varejao AS. Methods and protocols in peripheral nerve regeneration experimental research: Part IV—Kinematic gait analysis to quantify peripheral nerve regeneration in the rat. Int Rev Neurobiol. 2009;87:127–39.

    Article  PubMed  Google Scholar 

  13. Navarro X, Udina E. Methods and protocols in peripheral nerve regeneration experimental research: Part III—Electrophysiological evaluation. Int Rev Neurobiol. 2009;87:105–26.

    Article  PubMed  Google Scholar 

  14. Raimondo S, Fornaro M, Di Scipio F, Ronchi G, Giacobini-Robecchi MG, Geuna S. Methods and protocols in peripheral nerve regeneration experimental research: Part II—Morphological techniques. Int Rev Neurobiol. 2009;87:81–103.

    Article  PubMed  Google Scholar 

  15. Chan KM, Gordon T, Zochodne DW, Power HA. Improving peripheral nerve regeneration: from molecular mechanisms to potential therapeutic targets. Exp Neurol. 2014;261:826–35.

    Article  CAS  PubMed  Google Scholar 

  16. Grinsell D, Keating CP. Peripheral nerve reconstruction after injury: a review of clinical and experimental therapies. Biomed Res Int. 2014;2014:698256.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Isaacs J. Treatment of acute peripheral nerve injuries: current concepts. J Hand Surg Am. 2010;35(3):491–7.

    Article  PubMed  Google Scholar 

  18. Isaacs JE, McDaniel CO, Owen JR, Wayne JS. Comparative analysis of biomechanical performance of available “nerve glues”. J Hand Surg Am. 2008;33(6):893–9.

    Article  PubMed  Google Scholar 

  19. Siemionow M, Tetik C, Ozer K, Ayhan S, Siemionow K, Browne E. Epineural sleeve neurorrhaphy: surgical technique and functional results—a preliminary report. Ann Plast Surg. 2002;48(3):281–5.

    Article  PubMed  Google Scholar 

  20. Siemionow MZ, Eisenmann-Klein M. Plastic and reconstructive surgery. Berlin: Springer; 2010.

    Book  Google Scholar 

  21. Siemionow M, Bobkiewicz A, Cwykiel J, Uygur S, Francuzik W. Epineural sheath jacket as a new surgical technique for neuroma prevention in the rat sciatic nerve model. Ann Plast Surg. 2017;79(4):377–84.

    Article  CAS  PubMed  Google Scholar 

  22. Tsao B, Boulis N, Bethoux F, Murray B. Trauma of the nervous system. In: Daroff R, Fenichel G, Jankovic J, Mazziotta J, editors. Bradley’s neurology in clinical practice. 6th ed. Philadelphia: Elsevier; 2012. p. 984–1002.

    Chapter  Google Scholar 

  23. Colen KL, Choi M, Chiu DT. Nerve grafts and conduits. Plast Reconstr Surg. 2009;124(6 Suppl):e386–94.

    Article  CAS  PubMed  Google Scholar 

  24. Millesi H, Meissl G, Berger A. The interfascicular nerve-grafting of the median and ulnar nerves. J Bone Joint Surg Am. 1972;54(4):727–50.

    Article  CAS  PubMed  Google Scholar 

  25. Taylor GI, Ham FJ. The free vascularized nerve graft. A further experimental and clinical application of microvascular techniques. Plast Reconstr Surg. 1976;57(4):413–26.

    Article  CAS  PubMed  Google Scholar 

  26. Terzis JK, Kostopoulos VK. Vascularized nerve grafts and vascularized fascia for upper extremity nerve reconstruction. Hand (NY). 2010;5(1):19–30.

    Article  Google Scholar 

  27. Farnebo S, Thorfinn J, Dahlin L. Peripheral nerve injuries of the upper extremity. In: Neligan P, editor. Plastic surgery, vol. 6. Philadelphia: Elsevier; 2013. p. 694–718.

    Google Scholar 

  28. Mackinnon SE, Dellon AL. Surgery of the peripheral nerve. New York: Thieme Medical Publishers; 1988.

    Google Scholar 

  29. Norkus T, Norkus M, Ramanauskas T. Donor, recipient and nerve grafts in brachial plexus reconstruction: anatomical and technical features for facilitating the exposure. Surg Radiol Anat. 2005;27(6):524–30.

    Article  CAS  PubMed  Google Scholar 

  30. Millesi H. Peripheral nerve surgery today: turning point or continuous development? J Hand Surg Br. 1990;15(3):281–7.

    Article  CAS  PubMed  Google Scholar 

  31. Moore AM, Ray WZ, Chenard KE, Tung T, Mackinnon SE. Nerve allotransplantation as it pertains to composite tissue transplantation. Hand (NY). 2009;4(3):239–44.

    Article  Google Scholar 

  32. Ross D, Mackinnon SE, Chang YL. Intraneural anatomy of the median nerve provides “third web space” donor nerve graft. J Reconstr Microsurg. 1992;8(3):225–32.

    Article  CAS  PubMed  Google Scholar 

  33. Anderson PN, Turmaine M. Peripheral nerve regeneration through grafts of living and freeze-dried CNS tissue. Neuropathol Appl Neurobiol. 1986;12(4):389–99.

    Article  CAS  PubMed  Google Scholar 

  34. Evans PJ, Mackinnon SE, Best TJ, Wade JA, Awerbuck DC, Makino AP, Hunter DA, Midha R. Regeneration across preserved peripheral nerve grafts. Muscle Nerve. 1995;18(10):1128–38.

    Article  CAS  PubMed  Google Scholar 

  35. Lawson GM, Glasby MA. A comparison of immediate and delayed nerve repair using autologous freeze-thawed muscle grafts in a large animal model. The simple injury. J Hand Surg Br. 1995;20(5):663–700.

    Article  CAS  PubMed  Google Scholar 

  36. Doolabh VB, Mackinnon SE. FK506 accelerates functional recovery following nerve grafting in a rat model. Plast Reconstr Surg. 1999;103(7):1928–36.

    Article  CAS  PubMed  Google Scholar 

  37. Konofaos P, Terzis JK. FK506 and nerve regeneration: past, present, and future. J Reconstr Microsurg. 2013;29(3):141–8.

    Article  PubMed  Google Scholar 

  38. Gold BG. FK506 and the role of immunophilins in nerve regeneration. Mol Neurobiol. 1997;15(3):285–306.

    Article  CAS  PubMed  Google Scholar 

  39. Gold BG, Katoh K, Storm-Dickerson T. The immunosuppressant FK506 increases the rate of axonal regeneration in rat sciatic nerve. J Neurosci. 1995;15(11):7509–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Mackinnon SE, Doolabh VB, Novak CB, Trulock EP. Clinical outcome following nerve allograft transplantation. Plast Reconstr Surg. 2001;107(6):1419–29.

    Article  CAS  PubMed  Google Scholar 

  41. Sachanandani NF, Pothula A, Tung TH. Nerve gaps. Plast Reconstr Surg. 2014;133(2):313–9.

    Article  CAS  PubMed  Google Scholar 

  42. Konofaos P, Ver Halen JP. Nerve repair by means of tubulization: past, present, future. J Reconstr Microsurg. 2013;29(3):149–64.

    Article  CAS  PubMed  Google Scholar 

  43. Kehoe S, Zhang XF, Boyd D. FDA approved guidance conduits and wraps for peripheral nerve injury: a review of materials and efficacy. Injury. 2012;43(5):553–72.

    Article  CAS  PubMed  Google Scholar 

  44. Karacaoglu E, Yuksel F, Peker F, Guler MM. Nerve regeneration through an epineural sheath: its functional aspect compared with nerve and vein grafts. Microsurgery. 2001;21(5):196–201.

    Article  CAS  PubMed  Google Scholar 

  45. Chen YS, Chang JY, Cheng CY, Tsai FJ, Yao CH, Liu BS. An in vivo evaluation of a biodegradable genipin-cross-linked gelatin peripheral nerve guide conduit material. Biomaterials. 2005;26(18):3911–8.

    Article  CAS  PubMed  Google Scholar 

  46. Patel M, Mao L, Wu B, Vandevord PJ. GDNF-chitosan blended nerve guides: a functional study. J Tissue Eng Regen Med. 2007;1(5):360–7.

    Article  CAS  PubMed  Google Scholar 

  47. Uebersax L, Mattotti M, Papaloizos M, Merkle HP, Gander B, Meinel L. Silk fibroin matrices for the controlled release of nerve growth factor (NGF). Biomaterials. 2007;28(30):4449–60.

    Article  CAS  PubMed  Google Scholar 

  48. Jiang X, Lim SH, Mao HQ, Chew SY. Current applications and future perspectives of artificial nerve conduits. Exp Neurol. 2010;223(1):86–101.

    Article  PubMed  Google Scholar 

  49. Chiono V, Tonda-Turo C, Ciardelli G. Artificial scaffolds for peripheral nerve reconstruction. Int Rev Neurobiol. 2009;87:173–98.

    Article  CAS  PubMed  Google Scholar 

  50. Chen YS, Hsieh CL, Tsai CC, Chen TH, Cheng WC, Hu CL, Yao CH. Peripheral nerve regeneration using silicone rubber chambers filled with collagen, laminin and fibronectin. Biomaterials. 2000;21(15):1541–7.

    Article  CAS  PubMed  Google Scholar 

  51. Stanec S, Stanec Z. Reconstruction of upper-extremity peripheral-nerve injuries with ePTFE conduits. J Reconstr Microsurg. 1998;14(4):227–32.

    Article  CAS  PubMed  Google Scholar 

  52. Yan H, Zhang F, Chen MB, Lineaweaver WC. Conduit luminal additives for peripheral nerve repair. Int Rev Neurobiol. 2009;87:199–225.

    Article  CAS  PubMed  Google Scholar 

  53. Chen X, Wang XD, Chen G, Lin WW, Yao J, Gu XS. Study of in vivo differentiation of rat bone marrow stromal cells into Schwann cell-like cells. Microsurgery. 2006;26(2):111–5.

    Article  CAS  PubMed  Google Scholar 

  54. Raimondo S, Nicolino S, Tos P, Battiston B, Giacobini-Robecchi MG, Perroteau I, Geuna S. Schwann cell behavior after nerve repair by means of tissue-engineered muscle-vein combined guides. J Comp Neurol. 2005;489(2):249–59.

    Article  PubMed  Google Scholar 

  55. Nilsson A, Dahlin L, Lundborg G, Kanje M. Graft repair of a peripheral nerve without the sacrifice of a healthy donor nerve by the use of acutely dissociated autologous Schwann cells. Scand J Plast Reconstr Surg Hand Surg. 2005;39(1):1–6.

    Article  PubMed  Google Scholar 

  56. Evans GR, Brandt K, Katz S, Chauvin P, Otto L, Bogle M, Wang B, Meszlenyi RK, Lu L, Mikos AG, Patrick CW Jr. Bioactive poly(L-lactic acid) conduits seeded with Schwann cells for peripheral nerve regeneration. Biomaterials. 2002;23(3):841–8.

    Article  CAS  PubMed  Google Scholar 

  57. Mosahebi A, Wiberg M, Terenghi G. Addition of fibronectin to alginate matrix improves peripheral nerve regeneration in tissue-engineered conduits. Tissue Eng. 2003;9(2):209–18.

    Article  CAS  PubMed  Google Scholar 

  58. Keilhoff G, Goihl A, Stang F, Wolf G, Fansa H. Peripheral nerve tissue engineering: autologous Schwann cells vs. transdifferentiated mesenchymal stem cells. Tissue Eng. 2006;12(6):1451–165.

    Article  CAS  PubMed  Google Scholar 

  59. Nakayama K, Takakuda K, Koyama Y, Itoh S, Wang W, Mukai T, Shirahama N. Enhancement of peripheral nerve regeneration using bioabsorbable polymer tubes packed with fibrin gel. Artif Organs. 2007;31(7):500–8.

    Article  CAS  PubMed  Google Scholar 

  60. Matsumoto K, Ohnishi K, Kiyotani T, Sekine T, Ueda H, Nakamura T, Endo K, Shimizu Y. Peripheral nerve regeneration across an 80-mm gap bridged by a polyglycolic acid (PGA)-collagen tube filled with laminin-coated collagen fibers: a histological and electrophysiological evaluation of regenerated nerves. Brain Res. 2000;868(2):315–28.

    Article  CAS  PubMed  Google Scholar 

  61. Allmeling C, Jokuszies A, Reimers K, Kall S, Choi CY, Brandes G, Kasper C, Scheper T, Guggenheim M, Vogt PM. Spider silk fibres in artificial nerve constructs promote peripheral nerve regeneration. Cell Prolif. 2008;41(3):408–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Bunting S, Di Silvio L, Deb S, Hall S. Bioresorbable glass fibres facilitate peripheral nerve regeneration. J Hand Surg Br. 2005;30(3):242–7.

    Article  CAS  PubMed  Google Scholar 

  63. Xu X, Yee WC, Hwang PY, Yu H, Wan AC, Gao S, Boon KL, Mao HQ, Leong KW, Wang S. Peripheral nerve regeneration with sustained release of poly(phosphoester) microencapsulated nerve growth factor within nerve guide conduits. Biomaterials. 2003;24(13):2405–12.

    Article  CAS  PubMed  Google Scholar 

  64. Wood MD, Moore AM, Hunter DA, Tuffaha S, Borschel GH, Mackinnon SE, Sakiyama-Elbert SE. Affinity-based release of glial-derived neurotrophic factor from fibrin matrices enhances sciatic nerve regeneration. Acta Biomater. 2009;5(4):959–68.

    Article  CAS  PubMed  Google Scholar 

  65. Ohta M, Suzuki Y, Chou H, Ishikawa N, Suzuki S, Tanihara M, Suzuki Y, Mizushima Y, Dezawa M, Ide C. Novel heparin/alginate gel combined with basic fibroblast growth factor promotes nerve regeneration in rat sciatic nerve. J Biomed Mater Res A. 2004;71(4):661–8.

    Article  PubMed  CAS  Google Scholar 

  66. Zhang J, Lineaweaver WC, Oswald T, Chen Z, Chen Z, Zhang F. Ciliary neurotrophic factor for acceleration of peripheral nerve regeneration: an experimental study. J Reconstr Microsurg. 2004;20(4):323–7.

    Article  CAS  PubMed  Google Scholar 

  67. Hobson MI, Green CJ, Terenghi G. VEGF enhances intraneural angiogenesis and improves nerve regeneration after axotomy. J Anat. 2000;197(Pt 4):591–605.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Kalbermatten DF, Kingham PJ, Mahay D, Mantovani C, Pettersson J, Raffoul W, Balcin H, Pierer G, Terenghi G. Fibrin matrix for suspension of regenerative cells in an artificial nerve conduit. J Plast Reconstr Aesthet Surg. 2008;61(6):669–75.

    Article  CAS  PubMed  Google Scholar 

  69. Fansa H, Schneider W, Wolf G, Keilhoff G. Influence of insulin-like growth factor-I (IGF-I) on nerve autografts and tissue-engineered nerve grafts. Muscle Nerve. 2002;26(1):87–93.

    Article  CAS  PubMed  Google Scholar 

  70. AxoGen, Inc. Announces commercial release and first clinical implant of Avive™ soft tissue membrane. 2016. https://globenewswire.com/news-release/2016/11/21. Accessed 13 Aug 2017.

  71. Avive™ Soft Tissue Membrane. 2016. http://www.axogeninc.com/products. Accessed 13 Aug 2017.

  72. Lee SK, Wolfe SW. Nerve transfers for the upper extremity: new horizons in nerve reconstruction. J Am Acad Orthop Surg. 2012;20(8):506–17.

    Article  PubMed  Google Scholar 

  73. Tung TH, Mackinnon SE. Nerve transfers: indications, techniques, and outcomes. J Hand Surg Am. 2010;35(2):332–41.

    Article  PubMed  Google Scholar 

  74. Wong AH, Pianta TJ, Mastella DJ. Nerve transfers. Hand Clin. 2012;28(4):571–7.

    Article  CAS  PubMed  Google Scholar 

  75. Tos P, Colzani G, Ciclamini D, Titolo P, Pugliese P, Artiaco S. Clinical applications of end-to-side neurorrhaphy: an update. Biomed Res Int. 2014;2014:646128.

    Article  PubMed  PubMed Central  Google Scholar 

  76. Viterbo F, Trindade JC, Hoshino K, Mazzoni Neto A. End-to-side neurorrhaphy with removal of the epineural sheath: an experimental study in rats. Plast Reconstr Surg. 1994;94(7):1038–47.

    Article  CAS  PubMed  Google Scholar 

  77. Geuna S, Papalia I, Tos P. End-to-side (terminolateral) nerve regeneration: a challenge for neuroscientists coming from an intriguing nerve repair concept. Brain Res Rev. 2006;52(2):381–8.

    Article  PubMed  Google Scholar 

  78. Tos P, Artiaco S, Papalia I, Marcoccio I, Geuna S, Battiston B. End-to-side nerve regeneration: from the laboratory bench to clinical applications. Int Rev Neurobiol. 2009;87:281–94.

    Article  PubMed  Google Scholar 

  79. Brenner MJ, Dvali L, Hunter DA, Myckatyn TM, Mackinnon SE. Motor neuron regeneration through end-to-side repairs is a function of donor nerve axotomy. Plast Reconstr Surg. 2007;120(1):215–23.

    Article  CAS  PubMed  Google Scholar 

  80. Terzis JK, Tzafetta K. “Babysitter” procedure with concomitant muscle transfer in facial paralysis. Plast Reconstr Surg. 2009;124(4):1142–56.

    Article  CAS  PubMed  Google Scholar 

  81. Davidge KM, Yee A, Moore AM, Mackinnon SE. The supercharge end-to-side anterior interosseous-to-ulnar motor nerve transfer for restoring intrinsic function: clinical experience. Plast Reconstr Surg. 2015;136(3):344e–52e.

    Article  CAS  PubMed  Google Scholar 

  82. Elfar JC, Jacobson JA, Puzas JE, Rosier RN, Zuscik MJ. Erythropoietin accelerates functional recovery after peripheral nerve injury. J Bone Joint Surg Am. 2008;90(8):1644–53.

    Article  PubMed  PubMed Central  Google Scholar 

  83. Yan Y, Sun HH, Hunter DA, Mackinnon SE, Johnson PJ. Efficacy of short-term FK506 administration on accelerating nerve regeneration. Neurorehabil Neural Repair. 2012;26(6):570–80.

    Article  PubMed  Google Scholar 

  84. Kostopoulos VK, Davis CL, Terzis JK. Effects of acetylo-L-carnitine in end-to-side neurorrhaphy: a pilot study. Microsurgery. 2009;29(6):456–63.

    Article  PubMed  Google Scholar 

  85. Reid AJ, Shawcross SG, Hamilton AE, Wiberg M, Terenghi G. N-acetylcysteine alters apoptotic gene expression in axotomised primary sensory afferent subpopulations. Neurosci Res. 2009;65(2):148–55.

    Article  CAS  PubMed  Google Scholar 

  86. Mohammadi R, Hirsaee MA, Amini K. Improvement of functional recovery of transected peripheral nerve by means of artery grafts filled with diclofenac. Int J Surg. 2013;11(3):259–64.

    Article  PubMed  Google Scholar 

  87. Odaci E, Kaplan S. Melatonin and nerve regeneration. Int Rev Neurobiol. 2009;87:317–35.

    Article  CAS  PubMed  Google Scholar 

  88. Fleming CE, Saraiva MJ, Sousa MM. Transthyretin enhances nerve regeneration. J Neurochem. 2007;103(2):831–9.

    Article  CAS  PubMed  Google Scholar 

  89. Sun HH, Saheb-Al-Zamani M, Yan Y, Hunter DA, Mackinnon SE, Johnson PJ. Geldanamycin accelerated peripheral nerve regeneration in comparison to FK-506 in vivo. Neuroscience. 2012;223:114–23.

    Article  CAS  PubMed  Google Scholar 

  90. Udina E, Ladak A, Furey M, Brushart T, Tyreman N, Gordon T. Rolipram-induced elevation of cAMP or chondroitinase ABC breakdown of inhibitory proteoglycans in the extracellular matrix promotes peripheral nerve regeneration. Exp Neurol. 2010;223(1):143–52.

    Article  CAS  PubMed  Google Scholar 

  91. Sharma N, Coughlin L, Porter RG, Tanzer L, Wurster RD, Marzo SJ, Jones KJ, Foecking EM. Effects of electrical stimulation and gonadal steroids on rat facial nerve regenerative properties. Restor Neurol Neurosci. 2009;27(6):633–44.

    PubMed  Google Scholar 

  92. Madura T, Kubo T, Tanag M, Matsuda K, Tomita K, Yano K, Hosokawa K. The Rho-associated kinase inhibitor fasudil hydrochloride enhances neural regeneration after axotomy in the peripheral nervous system. Plast Reconstr Surg. 2007;119(2):526–35.

    Article  CAS  PubMed  Google Scholar 

  93. Zuo J, Neubauer D, Graham J, Krekoski CA, Ferguson TA, Muir D. Regeneration of axons after nerve transection repair is enhanced by degradation of chondroitin sulfate proteoglycan. Exp Neurol. 2002;176(1):221–8.

    Article  CAS  PubMed  Google Scholar 

  94. Kino T, Hatanaka H, Miyata S, Inamura N, Nishiyama M, Yajima T, Goto T, Okuhara M, Kohsaka M, Aoki H, et al. FK-506, a novel immunosuppressant isolated from a Streptomyces. II. Immunosuppressive effect of FK-506 in vitro. J Antibiot (Tokyo). 1987;40(9):1256–65.

    Article  CAS  Google Scholar 

  95. Wang MS, Zeleny-Pooley M, Gold BG. Comparative dose-dependence study of FK506 and cyclosporin A on the rate of axonal regeneration in the rat sciatic nerve. J Pharmacol Exp Ther. 1997;282(2):1084–93.

    CAS  PubMed  Google Scholar 

  96. Fairbairn NG, Meppelink AM, Ng-Glazier J, Randolph MA, Winograd JM. Augmenting peripheral nerve regeneration using stem cells: a review of current opinion. World J Stem Cells. 2015;7(1):11–26.

    Article  PubMed  PubMed Central  Google Scholar 

  97. Dezawa M, Takahashi I, Esaki M, Takano M, Sawada H. Sciatic nerve regeneration in rats induced by transplantation of in vitro differentiated bone-marrow stromal cells. Eur J Neurosci. 2001;14(11):1771–6.

    Article  CAS  PubMed  Google Scholar 

  98. Hong SQ, Zhang HT, You J, Zhang MY, Cai YQ, Jiang XD, Xu RX. Comparison of transdifferentiated and untransdifferentiated human umbilical mesenchymal stem cells in rats after traumatic brain injury. Neurochem Res. 2011;36(12):2391–400.

    Article  CAS  PubMed  Google Scholar 

  99. Cui L, Jiang J, Wei L, Zhou X, Fraser JL, Snider BJ, Yu SP. Transplantation of embryonic stem cells improves nerve repair and functional recovery after severe sciatic nerve axotomy in rats. Stem Cells. 2008;26(5):1356–65.

    Article  CAS  PubMed  Google Scholar 

  100. Lee EJ, Xu L, Kim GH, Kang SK, Lee SW, Park SH, Kim S, Choi TH, Kim HS. Regeneration of peripheral nerves by transplanted sphere of human mesenchymal stem cells derived from embryonic stem cells. Biomaterials. 2012;33(29):7039–46.

    Article  CAS  PubMed  Google Scholar 

  101. Craff MN, Zeballos JL, Johnson TS, Ranka MP, Howard R, Motarjem P, Randolph MA, Winograd JM. Embryonic stem cell-derived motor neurons preserve muscle after peripheral nerve injury. Plast Reconstr Surg. 2007;119(1):235–45.

    Article  CAS  PubMed  Google Scholar 

  102. Pan HC, Chen CJ, Cheng FC, Ho SP, Liu MJ, Hwang SM, Chang MH, Wang YC. Combination of G-CSF administration and human amniotic fluid mesenchymal stem cell transplantation promotes peripheral nerve regeneration. Neurochem Res. 2009;34(3):518–27.

    Article  CAS  PubMed  Google Scholar 

  103. Cheng FC, Tai MH, Sheu ML, Chen CJ, Yang DY, Su HL, Ho SP, Lai SZ, Pan HC. Enhancement of regeneration with glia cell line-derived neurotrophic factor-transduced human amniotic fluid mesenchymal stem cells after sciatic nerve crush injury. J Neurosurg. 2010;112(4):868–79.

    Article  CAS  PubMed  Google Scholar 

  104. Gartner A, Pereira T, Alves MG, Armada-da-Silva PA, Amorim I, Gomes R, Ribeiro J, Franca ML, Lopes C, Carvalho RA, Socorro S, Oliveira PF, Porto B, Sousa R, Bombaci A, Ronchi G, Fregnan F, Varejao AS, Luis AL, Geuna S, Mauricio AC. Use of poly(DL-lactide-epsilon-caprolactone) membranes and mesenchymal stem cells from the Wharton’s jelly of the umbilical cord for promoting nerve regeneration in axonotmesis: in vitro and in vivo analysis. Differentiation. 2012;84(5):355–65.

    Article  CAS  PubMed  Google Scholar 

  105. Guo BF, Dong MM. Application of neural stem cells in tissue-engineered artificial nerve. Otolaryngol Head Neck Surg. 2009;140(2):159–64.

    Article  PubMed  Google Scholar 

  106. Liard O, Segura S, Sagui E, Nau A, Pascual A, Cambon M, Darlix JL, Fusai T, Moyse E. Adult-brain-derived neural stem cells grafting into a vein bridge increases postlesional recovery and regeneration in a peripheral nerve of adult pig. Stem Cells Int. 2012;2012:128732.

    Article  PubMed  PubMed Central  Google Scholar 

  107. Johnson TS, O’Neill AC, Motarjem PM, Nazzal J, Randolph M, Winograd JM. Tumor formation following murine neural precursor cell transplantation in a rat peripheral nerve injury model. J Reconstr Microsurg. 2008;24(8):545–50.

    Article  PubMed  Google Scholar 

  108. McKenzie IA, Biernaskie J, Toma JG, Midha R, Miller FD. Skin-derived precursors generate myelinating Schwann cells for the injured and dysmyelinated nervous system. J Neurosci. 2006;26(24):6651–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Marchesi C, Pluderi M, Colleoni F, Belicchi M, Meregalli M, Farini A, Parolini D, Draghi L, Fruguglietti ME, Gavina M, Porretti L, Cattaneo A, Battistelli M, Prelle A, Moggio M, Borsa S, Bello L, Spagnoli D, Gaini SM, Tanzi MC, Bresolin N, Grimoldi N, Torrente Y. Skin-derived stem cells transplanted into resorbable guides provide functional nerve regeneration after sciatic nerve resection. Glia. 2007;55(4):425–38.

    Article  CAS  PubMed  Google Scholar 

  110. Amoh Y, Aki R, Hamada Y, Niiyama S, Eshima K, Kawahara K, Sato Y, Tani Y, Hoffman RM, Katsuoka K. Nestin-positive hair follicle pluripotent stem cells can promote regeneration of impinged peripheral nerve injury. J Dermatol. 2012;39(1):33–8.

    Article  CAS  PubMed  Google Scholar 

  111. Martens W, Sanen K, Georgiou M, Struys T, Bronckaers A, Ameloot M, Phillips J. Lambrichts human dental pulp stem cells can differentiate into Schwann cells and promote and guide neurite outgrowth in an aligned tissue-engineered collagen construct in vitro. FASEB J. 2014;28(4):1634–43.

    Article  PubMed  PubMed Central  Google Scholar 

  112. Salomone R, Bento RF, Costa HJ, Azzi-Nogueira D, Ovando PC, Da-Silva CF, Zanatta DB, Strauss BE, Haddad LA. Bone marrow stem cells in facial nerve regeneration from isolated stumps. Muscle Nerve. 2013;48(3):423–9.

    Article  CAS  PubMed  Google Scholar 

  113. Zhao Z, Wang Y, Peng J, Ren Z, Zhang L, Guo Q, Xu W, Lu S. Improvement in nerve regeneration through a decellularized nerve graft by supplementation with bone marrow stromal cells in fibrin. Cell Transplant. 2014;23(1):97–110.

    Article  PubMed  Google Scholar 

  114. di Summa PG, Kingham PJ, Raffoul W, Wiberg M, Terenghi G, Kalbermatten DF. Adipose-derived stem cells enhance peripheral nerve regeneration. J Plast Reconstr Aesthet Surg. 2010;63(9):1544–52.

    Article  PubMed  Google Scholar 

  115. Sun F, Zhou K, Mi WJ, Qiu JH. Repair of facial nerve defects with decellularized artery allografts containing autologous adipose-derived stem cells in a rat model. Neurosci Lett. 2011;499(2):104–8.

    Article  CAS  PubMed  Google Scholar 

  116. Ikeda M, Uemura T, Takamatsu K, Okada M, Kazuki K, Tabata Y, Ikada Y, Nakamura H. 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. 2014;102(5):1370–8.

    Article  PubMed  CAS  Google Scholar 

  117. Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, Jones JM. Embryonic stem cell lines derived from human blastocysts. Science. 1998;282(5391):1145–7.

    Article  CAS  PubMed  Google Scholar 

  118. Reynolds BA, Tetzlaff W, Weiss S. A multipotent EGF-responsive striatal embryonic progenitor cell produces neurons and astrocytes. J Neurosci. 1992;12(11):4565–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Paspala SA, Murthy TV, Mahaboob VS, Habeeb MA. Pluripotent stem cells—a review of the current status in neural regeneration. Neurol India. 2011;59(4):558–65.

    Article  PubMed  Google Scholar 

  120. Safford KM, Rice HE. Stem cell therapy for neurologic disorders: therapeutic potential of adipose-derived stem cells. Curr Drug Targets. 2005;6(1):57–62.

    Article  CAS  PubMed  Google Scholar 

  121. Guilak F, Lott KE, Awad HA, Cao Q, Hicok KC, Fermor B, Gimble JM. Clonal analysis of the differentiation potential of human adipose-derived adult stem cells. J Cell Physiol. 2006;206(1):229–37.

    Article  CAS  PubMed  Google Scholar 

  122. de Winter F, Hoyng S, Tannemaat M, Eggers R, Mason M, Malessy M, Verhaagen J. Gene therapy approaches to enhance regeneration of the injured peripheral nerve. Eur J Pharmacol. 2013;719(1–3):145–52.

    Article  PubMed  CAS  Google Scholar 

  123. Gordon T, Brushart TM, Chan KM. Augmenting nerve regeneration with electrical stimulation. Neurol Res. 2008;30(10):1012–22.

    Article  CAS  PubMed  Google Scholar 

  124. Gordon T, Amirjani N, Edwards DC, Chan KM. Brief post-surgical electrical stimulation accelerates axon regeneration and muscle reinnervation without affecting the functional measures in carpal tunnel syndrome patients. Exp Neurol. 2010;223(1):192–202.

    Article  PubMed  Google Scholar 

  125. Rochkind S. Phototherapy in peripheral nerve regeneration: from basic science to clinical study. Neurosurg Focus. 2009;26(2):E8.

    Article  PubMed  Google Scholar 

  126. Rochkind S, Geuna S, Shainberg A. Phototherapy and nerve injury: focus on muscle response. Int Rev Neurobiol. 2013;109:99–109.

    Article  PubMed  Google Scholar 

  127. Rochkind S, Shainberg A. Protective effect of laser phototherapy on acetylcholine receptors and creatine kinase activity in denervated muscle. Photomed Laser Surg. 2013;31(10):499–504.

    Article  CAS  PubMed  Google Scholar 

  128. Rochkind S, Geuna S, Shainberg A. Phototherapy in peripheral nerve injury: effects on muscle preservation and nerve regeneration. Int Rev Neurobiol. 2009;87:445–64.

    Article  PubMed  Google Scholar 

  129. Radtke C, Kocsis JD, Vogt PM. Transplantation of olfactory ensheathing cells for peripheral nerve regeneration. Int Rev Neurobiol. 2009;87:405–15.

    Article  CAS  PubMed  Google Scholar 

  130. Ramos LE, Zell JP. Rehabilitation program for children with brachial plexus and peripheral nerve injury. Semin Pediatr Neurol. 2000;7(1):52–7.

    Article  CAS  PubMed  Google Scholar 

  131. Scott KR, Ahmed A, Scott L, Kothari MJ. Rehabilitation of brachial plexus and peripheral nerve disorders. Handb Clin Neurol. 2013;110:499–514.

    Article  PubMed  Google Scholar 

  132. Smania N, Berto G, La Marchina E, Melotti C, Midiri A, Roncari L, Zenorini A, Ianes P, Picelli A, Waldner A, Faccioli S, Gandolfi M. Rehabilitation of brachial plexus injuries in adults and children. Eur J Phys Rehabil Med. 2012;48(3):483–506.

    CAS  PubMed  Google Scholar 

  133. Mavrogenis AF, Spyridonos SG, Antonopoulos D, Soucacos PN, Papagelopoulos PJ. Effect of sensory re-education after low median nerve complete transection and repair. J Hand Surg Am. 2009;34(7):1210–5.

    Article  PubMed  Google Scholar 

  134. Rosen B, Lundborg G. Sensory re-education after nerve repair: aspects of timing. Handchir Mikrochir Plast Chir. 2004;36(1):8–12.

    Article  CAS  PubMed  Google Scholar 

  135. Paula MH, Barbosa RI, Marcolino AM, Elui VM, Rosen B, Fonseca MC. Early sensory re-education of the hand after peripheral nerve repair based on mirror therapy: a randomized controlled trial. Braz J Phys Ther. 2016;20(1):58–65.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. First Department of Orthopaedics, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece

    Georgios N. Panagopoulos, Panayiotis D. Megaloikonomos & Andreas F. Mavrogenis

Authors
  1. Georgios N. Panagopoulos
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Panayiotis D. Megaloikonomos
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Andreas F. Mavrogenis
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Andreas F. Mavrogenis .

Editor information

Editors and Affiliations

  1. Department for Plastic Surgery and Hand Surgery, Division of Experimental Plastic Surgery, Technical University of Munich, Munich, Germany

    Dominik Duscher

  2. Private Practice, Tustin, CA, USA

    Melvin A. Shiffman

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Panagopoulos, G.N., Megaloikonomos, P.D., Mavrogenis, A.F. (2019). Current Trends and Future Perspectives for Peripheral Nerve Regeneration. In: Duscher, D., Shiffman, M.A. (eds) Regenerative Medicine and Plastic Surgery. Springer, Cham. https://doi.org/10.1007/978-3-030-19962-3_28

Download citation

Publish with us

Policies and ethics

Search

Navigation