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J Reconstr Microsurg 2014; 30(09): 607-616
DOI: 10.1055/s-0034-1372477
Original Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Nerve Regeneration: Is There an Alternative to Nervous Graft?

Rodrigo Guerra Sabongi
1   Department of Orthopedics and Traumatology, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil
,
Luiz Augusto Lucas Martins De Rizzo
2   Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil
,
Marcela Fernandes
3   Division of Hand Surgery, Department of Orthopedics and Traumatology, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil
,
Sandra Gomes Valente
3   Division of Hand Surgery, Department of Orthopedics and Traumatology, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil
,
João Baptista Gomes dos Santos
1   Department of Orthopedics and Traumatology, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil
,
Flávio Faloppa
1   Department of Orthopedics and Traumatology, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil
,
Vilnei Mattioli Leite
1   Department of Orthopedics and Traumatology, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil
› Author Affiliations
Further Information

Publication History

16 October 2013

26 January 2014

Publication Date:
04 August 2014 (online)

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Abstract

Background In nerve injury with nervous gap, no restitution method was found better than the autograft, however, it has the disadvantage of damaging a normal nerve to be used as a graft. Platelet-rich plasma (PRP) is a possible filler material for vein grafts used as conduits for nerve regeneration, preventing its collapse, and providing growth factors and osteoconductive proteins.

Methods Isogenic rats were randomly divided into three groups. They received nerve autografts (GRF), PRP-containing vein grafts or a sham operation. Outcomes were evaluated by the sciatic functional index (SFI), morphometric, and morphologic analyses of the nerve distal to the lesion, and the number of spinal cord motoneurons positive for retrograde Fluoro-Gold (Santa Cruz Biotechnology, Inc., Dallas, TX) tracer.

Results The PRP and GRF groups had lower SFI values than the control animals throughout the postoperative period. The SFI was significantly higher in the PRP group than the GRF group at 90 days postoperatively (p = 0.011). Fiber diameter and number of motoneurons were significantly decreased in both the PRP and GRF groups, as compared with the control.

Conclusion PRP within a vein conduit may be an effective alternative or adjuvant to GRF, the current preferred treatment for nerve injury with a nerve gap, and further investigations are required to fully define the role of PRP in nerve regeneration.

Keywords

nerve regeneration - platelet-rich plasma - nerve graft
 

  • References

  • 1 Millesi H, Meissl G, Berger A. Further experience with interfascicular grafting of the median, ulnar, and radial nerves. J Bone Joint Surg Am 1976; 58 (2) 209-218
    PubMedGoogle Scholar
  • 2 Haase J, Bjerre P, Simesen K. Median and ulnar nerve transections treated with microsurgical interfascicular cable grafting with autogenous sural nerve. J Neurosurg 1980; 53 (1) 73-84
    CrossrefPubMedGoogle Scholar
  • 3 Merle M, Amend P, Foucher G, Michon J. Plea for the primary microsurgical repair of peripheral nerve lesions. A comparative study of 150 injuries of the median or the ulnar nerve with a follow-up of more than 2 years [in French]. Chirurgie 1984; 110 (8–9) 761-771
    PubMedGoogle Scholar
  • 4 Novak CB, Kelly L, Mackinnon SE. Sensory recovery after median nerve grafting. J Hand Surg Am 1992; 17 (1) 59-68
    CrossrefPubMedGoogle Scholar
  • 5 Singh R, Mechelse K, Hop WC, Braakman R. Long-term results of transplantations to repair median, ulnar, and radial nerve lesions by a microsurgical interfascicular autogenous cable graft technique. Surg Neurol 1992; 37 (6) 425-431
    CrossrefPubMedGoogle Scholar
  • 6 Brushart TME. The mechanical and humoral control of specificity in nerve repair. In: Gelberman R, , ed. Operative Nerve Repair and Reconstruction. Philadelphia: JB Lippincott; 1991: 215-230
    Google Scholar
  • 7 Grecco MAS, Leite VM, Albertoni WM , et al. Estudo da regeneração nervosa em nervos tibiais de ratos Wistar utilizando o Fluoro-Gold® como marcador neuronal. Acta Ortop Bras. 2003; 11 (4) 225-229
    PubMedGoogle Scholar
  • 8 Lolley RD, Bose WJ, Bastian F, Bassam B, Meyer FN, Anderson LD. Vein, silastic, and polyglycolic acid fine mesh: a comparative study in peripheral nerve repair. Ann Plast Surg 1995; 35 (3) 266-271
    CrossrefPubMedGoogle Scholar
  • 9 Millesi H. Nerve grafting. Clin Plast Surg 1984; 11 (1) 105-113
    PubMedGoogle Scholar
  • 10 Millesi H. Forty-two years of peripheral nerve surgery. Microsurgery 1993; 14 (4) 228-233
    CrossrefPubMedGoogle Scholar
  • 11 Battiston B, Geuna S, Ferrero M, Tos P. Nerve repair by means of tubulization: literature review and personal clinical experience comparing biological and synthetic conduits for sensory nerve repair. Microsurgery 2005; 25 (4) 258-267
    CrossrefPubMedGoogle Scholar
  • 12 Chiu DT, Strauch B. A prospective clinical evaluation of autogenous vein grafts used as a nerve conduit for distal sensory nerve defects of 3 cm or less. Plast Reconstr Surg 1990; 86 (5) 928-934
    CrossrefPubMedGoogle Scholar
  • 13 Lohmeyer JA, Kern Y, Schmauss D , et al. Prospective Clinical Study on Digital Nerve Repair with Collagen Nerve Conduits and Review of Literature. J Reconstr Microsurg 2013; ; [Epub ahead of print]
    PubMedGoogle Scholar
  • 14 Konofaos P, Ver Halen JP. Nerve repair by means of tubulization: past, present, future. J Reconstr Microsurg 2013; 29 (3) 149-164
    Article in Thieme ConnectPubMedGoogle Scholar
  • 15 Diao E, Peimer CA. Sutureless methods of nerve repair. Philadelphia: JB Lippincott; 1991: 309
    Google Scholar
  • 16 Longo FM, Manthorpe M, Skaper SD, Lundborg G, Varon S. Neuronotrophic activities accumulate in vivo within silicone nerve regeneration chambers. Brain Res 1983; 261 (1) 109-116
    CrossrefPubMedGoogle Scholar
  • 17 Politis MJ, Ederle K, Spencer PS. Tropism in nerve regeneration in vivo. Attraction of regenerating axons by diffusible factors derived from cells in distal nerve stumps of transected peripheral nerves. Brain Res 1982; 253 (1-2) 1-12
    CrossrefPubMedGoogle Scholar
  • 18 Mackinnon SE, Dellon AL. A study of nerve regeneration across synthetic (Maxon) and biologic (collagen) nerve conduits for nerve gaps up to 5 cm in the primate. J Reconstr Microsurg 1990; 6 (2) 117-121
    Article in Thieme ConnectPubMedGoogle Scholar
  • 19 Colonna M, Anastasi GP, Cavallaro G, Signorini M, Tomasello F. Nerve regeneration through autogenous vein grafts: an SEM evaluation. J Reconstr Microsurg 1996; 12 (4) 205-210
    Article in Thieme ConnectPubMedGoogle Scholar
  • 20 Ferrari F, De Castro Rodrigues A, Malvezzi CK, Dal Pai Silva M, Padovani CR. Inside-out vs. standard vein graft to repair a sensory nerve in rats. Anat Rec 1999; 256 (3) 227-232
    CrossrefPubMedGoogle Scholar
  • 21 Brunelli GA, Vigasio A, Brunelli GR. Different conduits in peripheral nerve surgery. Microsurgery 1994; 15 (3) 176-178
    CrossrefPubMedGoogle Scholar
  • 22 Fernandes M, Valente SG, Amado D , et al. Comparative study between autogenous graft and muscular graft covered with autogenous vein tube in Wister rats tibial nerves using the Fluoro-Gold® as a neuronal marker. Acta Ortop Bras. 2007; 15 (2) 97-100
    PubMedGoogle Scholar
  • 23 Marx RE. Platelet-rich plasma: evidence to support its use. J Oral Maxillofac Surg 2004; 62 (4) 489-496
    CrossrefPubMedGoogle Scholar
  • 24 Crovetti G, Martinelli G, Issi M , et al. Platelet gel for healing cutaneous chronic wounds. Transfus Apheresis Sci 2004; 30 (2) 145-151
    CrossrefPubMedGoogle Scholar
  • 25 Haynesworth SE, Kadiyala S, Liang L , et al. Chemiotactic and mitogenic stimulation of human mesenchymal stem cells by platelet rich plasma suggest a mechanism for enhancement of bone repair. Paper presented at: 48th Annual Meeting of the Orthopaedic Research Society; February 10–13, 2002; Dallas, TX
    PubMedGoogle Scholar
  • 26 Henderson JL, Cupp CL, Ross EV , et al. The effects of autologous platelet gel on wound healing. Ear Nose Throat J 2003; 82 (8) 598-602
    PubMedGoogle Scholar
  • 27 Beca T, Hernández G, Morante S, Bascones A. Platelet rich plasma: A review of literature. Av Periodon Implantol. 2007; 19 (1) 39-52
    PubMedGoogle Scholar
  • 28 Sant'Ana AC, Marques MM, Barroso TE, Passanezi E, de Rezende ML. Effects of TGF-beta1, PDGF-BB, and IGF-1 on the rate of proliferation and adhesion of a periodontal ligament cell lineage in vitro. J Periodontol 2007; 78 (10) 2007-2017
    CrossrefPubMedGoogle Scholar
  • 29 Green DM, Klink B. Platelet gel as an intraoperatively procured platelet-based alternative to fibrin glue. Plast Reconstr Surg 1998; 101 (4) 1161-1162
    CrossrefPubMedGoogle Scholar
  • 30 Antoniades HN, Williams LT. Human platelet-derived growth factor: structure and function. Fed Proc 1983; 42 (9) 2630-2634
    PubMedGoogle Scholar
  • 31 Dvorak HF, Brown LF, Detmar M, Dvorak AM. Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis. Am J Pathol 1995; 146 (5) 1029-1039
    PubMedGoogle Scholar
  • 32 Liu Y, Kalén A, Risto O, Wahlström O. Fibroblast proliferation due to exposure to a platelet concentrate in vitro is pH dependent. Wound Repair Regen 2002; 10 (5) 336-340
    CrossrefPubMedGoogle Scholar
  • 33 Robson MC. The role of growth factors in the healing of chronic wounds. Wound Repair Regen 1997; 5 (1) 12-17
    CrossrefPubMedGoogle Scholar
  • 34 Vendramin FS, Franco D, Nogueira CM, Pereira MS, Franco TR. Platelet-rich plasma and growth factors: processing technique and application in plastic surgery. Rev Col Bras Cir 2006; 33: 24-28
    PubMedGoogle Scholar
  • 35 Bhanot S, Alex JC. Current applications of platelet gels in facial plastic surgery. Facial Plast Surg 2002; 18 (1) 27-33
    Article in Thieme ConnectPubMedGoogle Scholar
  • 36 Freymiller EG, Aghaloo TL. Platelet-rich plasma: ready or not?. J Oral Maxillofac Surg 2004; 62 (4) 484-488
    CrossrefPubMedGoogle Scholar
  • 37 Linkhart TA, Mohan S, Baylink DJ. Growth factors for bone growth and repair: IGF, TGF beta and BMP. Bone 1996; 19 (1) 1S-12S
    CrossrefPubMedGoogle Scholar
  • 38 Man D, Plosker H, Winland-Brown JE. The use of autologous platelet-rich plasma (platelet gel) and autologous platelet-poor plasma (fibrin glue) in cosmetic surgery. Plast Reconstr Surg 2001; 107 (1) 229-237 , discussion 238–239
    CrossrefPubMedGoogle Scholar
  • 39 Mazzucco L, Medici D, Serra M , et al. The use of autologous platelet gel to treat difficult-to-heal wounds: a pilot study. Transfusion 2004; 44 (7) 1013-1018
    CrossrefPubMedGoogle Scholar
  • 40 Rossi Júnior R, Souza Filho MAP. Obtainment of autologous thrombin: proposition of simplify protocol and easy clinic reproduction. Rev Paul Odontol 2004; 26: 4-9
    PubMedGoogle Scholar
  • 41 de Medinaceli L, Freed WJ, Wyatt RJ. An index of the functional condition of rat sciatic nerve based on measurements made from walking tracks. Exp Neurol 1982; 77 (3) 634-643
    CrossrefPubMedGoogle Scholar
  • 42 Bain JR, Mackinnon SE, Hunter DA. Functional evaluation of complete sciatic, peroneal, and posterior tibial nerve lesions in the rat. Plast Reconstr Surg 1989; 83 (1) 129-138
    CrossrefPubMedGoogle Scholar
  • 43 Fernandes M, Valente SG, Fernandes MJS , et al. Bone marrow cells are able to increase vessels number during repair of sciatic nerve lesion. J Neurosci Methods 2008; 170 (1) 16-24
    CrossrefPubMedGoogle Scholar
  • 44 Brushart TME. Motor axons preferentially reinnervate motor pathways. J Neurosci 1993; 13 (6) 2730-2738
    Google Scholar
  • 45 Abercrombie M. Estimation of nuclear population from microtome sections. Anat Rec 1946; 94: 239-247
    CrossrefPubMedGoogle Scholar
  • 46 Winer BJ. Statistical Principles in Experimental Design. Tokyo: McGraw-Hill; 1971. 2.
    Google Scholar
  • 47 Oliveira EF, Mazzer N, Barbieri CH, DelBel EA. The use of a muscle graft to repair a segmentary nerve defect. An experimental study using the sciatic nerve of rats as model. J Neurosci Methods 2004; 133 (1-2) 19-26
    CrossrefPubMedGoogle Scholar
  • 48 Rafiuddin Ahmed M, Jayakumar R. Peripheral nerve regeneration in RGD peptide incorporated collagen tubes. Brain Res 2003; 993 (1-2) 208-216
    CrossrefPubMedGoogle Scholar
  • 49 Komiyama T, Nakao Y, Toyama Y, Vacanti CA, Vacanti MP, Ignotz RA. Novel technique for peripheral nerve reconstruction in the absence of an artificial conduit. J Neurosci Methods 2004; 134 (2) 133-140
    CrossrefPubMedGoogle Scholar
  • 50 Dellon AL, Mackinnon SE. Selection of the appropriate parameter to measure neural regeneration. Ann Plast Surg 1989; 23 (3) 197-202
    CrossrefPubMedGoogle Scholar
  • 51 Schröder JM. Altered ratio between axon diameter and myelin sheath thickness in regenerated nerve fibers. Brain Res 1972; 45 (1) 49-65
    CrossrefPubMedGoogle Scholar
  • 52 Friede RL, Samorajski T. Relation between the number of myelin lamellae and axon circumference in fibers of vagus and sciatic nerves of mice. J Comp Neurol 1967; 130 (3) 223-231
    CrossrefPubMedGoogle Scholar
  • 53 Sunitha Raja V, Munirathnam Naidu E. Platelet-rich fibrin: evolution of a second-generation platelet concentrate. Indian J Dent Res 2008; 19 (1) 42-46
    CrossrefPubMedGoogle Scholar
  • 54 Farrag TY, Lehar M, Verhaegen P, Carson KA, Byrne PJ. Effect of platelet rich plasma and fibrin sealant on facial nerve regeneration in a rat model. Laryngoscope 2007; 117 (1) 157-165
    CrossrefPubMedGoogle Scholar
  • 55 Elgazzar RF, Mutabagani MA, Abdelaal SE, Sadakah AA. Platelet rich plasma may enhance peripheral nerve regeneration after cyanoacrylate reanastomosis: a controlled blind study on rats. Int J Oral Maxillofac Surg 2008; 37 (8) 748-755
    CrossrefPubMedGoogle Scholar
  • 56 Sariguney Y, Yavuzer R, Elmas C, Yenicesu I, Bolay H, Atabay K. Effect of platelet-rich plasma on peripheral nerve regeneration. J Reconstr Microsurg 2008; 24 (3) 159-167
    Google Scholar
  • 57 Ding XG, Li SW, Zheng XM, Hu LQ, Hu WL, Luo Y. The effect of platelet-rich plasma on cavernous nerve regeneration in a rat model. Asian J Androl 2009; 11 (2) 215-221
    CrossrefPubMedGoogle Scholar
  • 58 Gosens T, Peerbooms JC, van Laar W, den Oudsten BL. Ongoing positive effect of platelet-rich plasma versus corticosteroid injection in lateral epicondylitis: a double-blind randomized controlled trial with 2-year follow-up. Am J Sports Med 2011; 39 (6) 1200-1208
    CrossrefPubMedGoogle Scholar
  • 59 Krogh TP, Fredberg U, Stengaard-Pedersen K, Christensen R, Jensen P, Ellingsen T. Treatment of lateral epicondylitis with platelet-rich plasma, glucocorticoid, or saline: a randomized, double-blind, placebo-controlled trial. Am J Sports Med 2013; 41 (3) 625-635
    CrossrefPubMedGoogle Scholar
  • 60 Creaney L, Wallace A, Curtis M, Connell D. Growth factor-based therapies provide additional benefit beyond physical therapy in resistant elbow tendinopathy: a prospective, single-blind, randomised trial of autologous blood injections versus platelet-rich plasma injections. Br J Sports Med 2011; 45 (12) 966-971
    CrossrefPubMedGoogle Scholar
  • 61 Thanasas C, Papadimitriou G, Charalambidis C, Paraskevopoulos I, Papanikolaou A. Platelet-rich plasma versus autologous whole blood for the treatment of chronic lateral elbow epicondylitis: a randomized controlled clinical trial. Am J Sports Med 2011; 39 (10) 2130-2134
    CrossrefPubMedGoogle Scholar
  • 62 Foster TE, Puskas BL, Mandelbaum BR, Gerhardt MB, Rodeo SA. Platelet-rich plasma: from basic science to clinical applications. Am J Sports Med 2009; 37 (11) 2259-2272
    CrossrefPubMedGoogle Scholar
  • 63 Yu W, Wang J, Yin J. Platelet-rich plasma: a promising product for treatment of peripheral nerve regeneration after nerve injury. Int J Neurosci 2011; 121 (4) 176-180
    CrossrefPubMedGoogle Scholar