Platelet-Rich Fibrin Conduits as an Alternative to Nerve Autografts for Peripheral Nerve Repair

Abstract

Background Peripheral nerves have limited regeneration capacity despite best efforts. Platelet-rich fibrin (PRF) contains growth factors that may stimulate peripheral nerve regeneration. This study verified whether nerve regeneration using autogenous vein conduits filled with PRF is comparable to autologous nerve graft, which is the standard treatment.

Methods The sciatic nerve of the right paw of inbred rats was dissected, and a 10-mm segment was removed from rats randomized to receive autologous nerve graft (GRAFT) or vein conduit filled with PRF (PRF). A third group (SHAM) underwent surgery without nerve resection. The sciatic functional index (SFI) was measured 0, 30, 60, and 90 days postsurgery. Morphometry and morphology of the distal nerve injury were examined. Motor neurons in the anterior horn of spinal cord stained with FluoroGold and counted.

Results No significant difference in SFI was observed between the GRAFT and PRF groups at any time point (all p > 0.05); however, SFI was lower in both groups compared with SHAM (p < 0.05). Morphometric and morphologic indexes were not significantly different between the GRAFT and PRF groups (p > 0.05); however, nerve fibers, axons, and myelin sheaths were thinner in both groups compared with SHAM (p = 0.0001). Average motor neurons' count was similar between the GRAFT and PRF groups (p = 0.91); the count was lower in both groups compared with SHAM (p = 0.002 and p = 0.001), respectively.

Conclusion Autologous nerve GRAFT and PRF-filled autogenous vein conduits were associated with similar outcomes, and worse than those observed in SHAM controls. Vein conduits filled with PRF may be a favorable alternative treatment to nerve grafts.

Keywords

nerve regeneration - platelet-rich fibrin - conduits - nerve grafts

• References

• 1 Zheng C, Zhu Q, Liu X. , et al. Improved peripheral nerve regeneration using acellular nerve allografts loaded with platelet-rich plasma. Tissue Eng Part A 2014; 20 (23-24): 3228-3240
• 2 Griffin JW, Hogan MV, Chhabra AB, Deal DN. Peripheral nerve repair and reconstruction. J Bone Joint Surg Am 2013; 95 (23) 2144-2151
• 3 Boyd KU, Nimigan AS, Mackinnon SE. Nerve reconstruction in the hand and upper extremity. Clin Plast Surg 2011; 38 (04) 643-660
• 4 Al-Qattan MM. End-to-side nerve repair. J Hand Surg Am 2002; 27 (04) 739 , author reply 739–740
• 5 Moore AM, Kasukurthi R, Magill CK, Farhadi HF, Borschel GH, Mackinnon SE. Limitations of conduits in peripheral nerve repairs. Hand (NY) 2009; 4 (02) 180-186
• 6 Fernandes M, Valente SG, Fernandes MJ. , et al. Bone marrow cells are able to increase vessels number during repair of sciatic nerve lesion. J Neurosci Methods 2008; 170 (01) 16-24
• 7 Dohan DM, Choukroun J, Diss A. , et al. Platelet-rich fibrin (PRF): a second-generation platelet concentrate. Part I: technological concepts and evolution. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2006; 101 (03) e37-e44
• 8 Dohan DM, Choukroun J, Diss A. , et al. Platelet-rich fibrin (PRF): a second-generation platelet concentrate. Part II: platelet-related biologic features. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2006; 101 (03) e45-e50
• 9 Piskin A, Kaplan S, Aktaş A. , et al. Platelet gel does not improve peripheral nerve regeneration: an electrophysiological, stereological, and electron microscopic study. Microsurgery 2009; 29 (02) 144-153
• 10 Sabongi RG, De Rizzo LA, Fernandes M. , et al. Nerve regeneration: is there an alternative to nervous graft?. J Reconstr Microsurg 2014; 30 (09) 607-616
• 11 Dohan Ehrenfest DM, Andia I, Zumstein MA, Zhang CQ, Pinto NR, Bielecki T. Classification of platelet concentrates (platelet-rich plasma-PRP, platelet-rich fibrin-PRF) for topical and infiltrative use in orthopedic and sports medicine: current consensus, clinical implications and perspectives. Muscles Ligaments Tendons J 2014; 4 (01) 3-9
• 12 Lichtenfels M, Colomé L, Sebben AD, Braga-Silva J. Effect of platelet rich plasma and platelet rich fibrin on sciatic nerve regeneration in a rat model. Microsurgery 2013; 33 (05) 383-390
• 13 Winer BJ. Statistical Principles in Experimental Design. Vol. 2. New York: McGrawHill; 1971
• 14 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
• 15 Rafiuddin Ahmed M, Jayakumar R. Peripheral nerve regeneration in RGD peptide incorporated collagen tubes. Brain Res 2003; 993 (1-2): 208-216
• 16 Dellon AL, Mackinnon SE. Selection of the appropriate parameter to measure neural regeneration. Ann Plast Surg 1989; 23 (03) 197-202
• 17 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 (03) 223-231
• 18 Mohammadi R, Amini K, Eskafian H. Betamethasone-enhanced vein graft conduit accelerates functional recovery in the rat sciatic nerve gap. J Oral Maxillofac Surg 2013; 71 (04) 786-792
• 19 Mohammadi R, Amini K, Yousefi A, Abdollahi-Pirbazari M, Belbasi A, Abedi F. Functional effects of local administration of thyroid hormone combined with chitosan conduit after sciatic nerve transection in rats. J Oral Maxillofac Surg 2013; 71 (10) 1763-1776
• 20 Emel E, Ergün SS, Kotan D. , et al. Effects of insulin-like growth factor-I and platelet-rich plasma on sciatic nerve crush injury in a rat model. J Neurosurg 2011; 114 (02) 522-528
• 21 Orbay H, Uysal AC, Hyakusoku H, Mizuno H. Differentiated and undifferentiated adipose-derived stem cells improve function in rats with peripheral nerve gaps. J Plast Reconstr Aesthet Surg 2012; 65 (05) 657-664
• 22 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 (02) 111-115
• 23 Wang D, Liu XL, Zhu JK. , et al. Repairing large radial nerve defects by acellular nerve allografts seeded with autologous bone marrow stromal cells in a monkey model. J Neurotrauma 2010; 27 (10) 1935-1943
• 24 Berrocal YA, Almeida VW, Gupta R, Levi AD. Transplantation of Schwann cells in a collagen tube for the repair of large, segmental peripheral nerve defects in rats. J Neurosurg 2013; 119 (03) 720-732
• 25 Jiang H, Qu W, Li Y, Zhong W, Zhang W. Platelet-derived growth factors-BB and fibroblast growth factors-base induced proliferation of Schwann cells in a 3D environment. Neurochem Res 2013; 38 (02) 346-355
• 26 Oya T, Zhao YL, Takagawa K. , et al. Platelet-derived growth factor-b expression induced after rat peripheral nerve injuries. Glia 2002; 38 (04) 303-312
• 27 Eccleston PA, Funa K, Heldin CH. Expression of platelet-derived growth factor (PDGF) and PDGF alpha- and beta-receptors in the peripheral nervous system: an analysis of sciatic nerve and dorsal root ganglia. Dev Biol 1993; 155 (02) 459-470
• 28 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 (04) 176-180
• 29 Bielecki T, Dohan Ehrenfest DM. Platelet-rich plasma (PRP) and platelet-rich fibrin (PRF): surgical adjuvants, preparations for in situ regenerative medicine and tools for tissue engineering. Curr Pharm Biotechnol 2012; 13 (07) 1121-1130
• 30 Dohan Ehrenfest DM, Bielecki T, Jimbo R. , et al. Do the fibrin architecture and leukocyte content influence the growth factor release of platelet concentrates? An evidence-based answer comparing a pure platelet-rich plasma (P-PRP) gel and a leukocyte- and platelet-rich fibrin (L-PRF). Curr Pharm Biotechnol 2012; 13 (07) 1145-1152