The effect of Mesenchymal Stem Cells and Surgical Angiogenesis on Functional Recovery of Decellularized Nerve Allografts in a Rabbit Peroneal Nerve Defect Model
Tara Sara Saffari, MD, MSc1,2, Guilherme Giusti, M.D.3, Tiam Mana Saffari, MD, PhD, MSc1 and Alexander Y Shin, MD1, 1Mayo Clinic, Rochester, MN, 2Radboud University, Nijmegen, Gelderland, Netherlands, 3Southeast Orthopedic Specialists, Jacksonville, FL
Background: Nerve regeneration after nerve injury is thought to be enhanced through the interaction of mesenchymal stem cells (MSCs) and surgical angiogenesis. Each treatment separately has resulted in improved nerve regeneration in rat nerve defect models. The purpose of this study was to investigate the effect of MSCs and surgical angiogenesis, alone or in combination, on functional recovery in a larger animal model for clinically relevant translation.
Methods: Ninety New Zealand White rabbits were divided into five groups of 18 animals each. Unilateral 3-cm peroneal nerve defects were repaired with (i) autografts, (ii), decellularized allografts, (iii) decellularized allografts vascularized with a superficial inferior epigastric fascial (SIEF) flap, (iv) decellularized allografts seeded with MSCs or (v) decellularized allografts seeded with MSCs and vascularized with a SIEF flap. Sixteen and 24 weeks after surgery, nerve regeneration was assessed using electrophysiology (compound muscle action potential), muscle force measurement (isometric tetanic force), wet muscle weight, ankle contracture angle, and weight ratio pre-operative compared to sacrifice. Serial ultrasonography was used to evaluate muscle atrophy and reinnervation by measuring the cross-sectional muscle area.
Results: Autografts were found to be significantly superior compared to all groups at 16 weeks with respect to cross-sectional muscle area, electrophysiology, muscle force measurement, and wet muscle weight (p<0.05 for all comparisons). Surgical angiogenesis of allografts were statistically comparable to autografts at 24 weeks with respect to cross-sectional muscle area (p=0.06), electrophysiology (p=0.07), muscle force measurement (p=0.24), and wet muscle weight (p=0.19). Autografts were significantly superior to all other groups at 24 weeks (p<0.05 for all comparisons). No differences were found in the ankle contracture angle or the weight ratio pre-operative compared to sacrifice between all groups for both time points. Normalization of all parameters was not observed at 24 weeks.
Conclusion: Surgical angiogenesis with an adipofascial flap to the nerve allograft successfully improves functional recovery in a long nerve gap model, comparable to the nerve autograft. Stem cells, alone or in combination with surgical angiogenesis, did not alter functional outcomes. Longer time points are needed to adequately assess the long-term outcomes. This study suggests that surgical angiogenesis is more important in improving nerve regeneration compared to cellular modulation of the nerve micro-environment.
Figure 1: The SIEF flap raised medially, showing the intact SIE vessels.
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