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Revascularization Patterns of Nerve Allografts in A Rat Sciatic Nerve Defect Model
Mana Saffari, MD^1,2, Femke Mathot, MD^1,3, Allen T. Bishop, MD⁴ and Alexander Y. Shin, MD⁵, (1)Mayo Clinic, Rochester, MN, (2)Erasmus MC, Rotterdam, Netherlands, (3)Radboud Universiteit, Nijmegen, Netherlands, (4)Microvascular Research Laboratory, Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, (5)Department of Orthopedic Surgery, Microvascular Research Laboratory, Mayo Clinic, Rochester, MN

Abstract

Introduction: After a nerve defect is bridged with an allograft nerve, neovascularization precedes neural changes to produce a supportive microenvironment for nerve regeneration to occur. Little is known about the revascularization patterns after such an injury. The aim of this study was to explore the revascularization patterns after surgical angiogenesis of a nerve allograft at various time points.

Materials and Methods: In 51 Lewis rats, 10 mm sciatic nerve gaps were repaired with a (i) nerve autograft, (ii) nerve allograft and (iii) surgically revascularized nerve allograft using a pedicled superficial inferior epigastric artery fascia flap (SIEF). At two, 12 and 16 weeks, the rats were sacrificed and Microfil® compound was injected to preserve vascularization. With micro computed tomography (micro CT), the vascular volume was measured in harvested nerve samples and compared to the unoperated side. Cross-sectional images were obtained over the length of the nerve. These images were divided into three concentric rings and the number of vessels in each ring was counted in the proximal, mid and distal sections of the nerve samples.

Results: At two weeks, the vascular volume in control nerves was superior to autograft and allograft, and similar to revascularized allograft nerves (SIEF group). At 12 weeks, the vascular volume in SIEF nerves was statistically higher than allografts (P<0.05) and at 16 weeks the volume in SIEF nerves was superior compared to other groups (P<0.0001). The cross-sectional images showed that the number of vessels in surgically revascularized allografts was statistically increased compared to allografts alone in all rings in the proximal section of the graft. In the mid-section of the graft, the number was statistically superior in the middle and central ring. No significant differences between groups were seen in the distal section of the nerve grafts. At sixteen weeks, these patterns were more evidently significant.

Conclusions: Surgical angiogenesis of nerve allografts greatly improves revascularization. In this study revascularization occurred primarily from proximal to distal (proximal inosculation) and not from both ends as previously believed. It also confirms the theory of centripetal revascularization.