Vascularization is delayed in long nerve constructs compared with nerve grafts

Abstract

Introduction: Nerve regeneration across nerve constructs, such as acellular nerve allografts (ANAs), is inferior to nerve auto/isografts especially in the case of long defect lengths. Vascularization may contribute to poor regeneration. The time course of vascular perfusion within long grafts and constructs was tracked to determine vascularization.

Methods: Male Lewis rat sciatic nerves were transected and repaired with 6 cm isografts or ANAs. At variable days following grafting, animals were perfused with Evans Blue albumin, and grafts were evaluated for vascular perfusion by a blinded observer.

Results: Vascularization at mid-graft was re-established within 3-4 days in 6 cm isografts, while it was established after 10 days in 6 cm ANAs.

Conclusions: Vascular perfusion is reestablished over a shorter time course in long isografts when compared with long ANAs. The differences in vascularization of long ANAs compared with auto/isografts suggest regenerative outcomes across ANAs could be affected by vascularization rates. Muscle Nerve 54: 319-321, 2016.

Keywords: acellular nerve allograft; autograft; hypoxia; ischemia; peripheral nerve; vascular perfusion.

Figure 1. Vascularization micrographs and quantification of time to mid-graft perfusion in long nerve grafts

Photomicrographs of longitudinal nerve graft sections after perfusion with EBA and CD31 staining (A–F). Vascular perfusion into the middle of the isograft began by 3 days (A) and was well-established with minimal leakage of EBA by 5 days (B, G). Vascular perfusion was only present in the proximal and distal graft regions of long ANAs at 10 days (D) and completed by 20 days (E, G). Both grafts demonstrated the presence of endothelial cells (CD31) at 5 days regardless of perfusion status (C, F). Arrows indicate perfused, patent vessels, while asterisks indicate leakage of EBA.