End-to-Side Neurorrhaphy as Schwann Cells Provider to Acellular Nerve Allograft and Its Suitable Application.

Hidekazu Yoshizawa,Rica Tanaka,Ayato Hayashi,Hiroshi Mizuno,Daiki Senda,Yuhei Natori,Nic D Leipzig

doi:10.1371/journal.pone.0167507

Abstract

Axonal regeneration relies on support from proliferating host Schwann cells (SCs), and previous studies on acellular nerve allografts (ANGs) suggest that axons can regenerate into ANGs within a limited distance. Numerous studies have demonstrated that the supplementation of ANGs with exogenous factors, such as cultured SCs, stem cells, and growth factors, promote nerve regeneration in ANGs. However, there are several problems associated with their utilization. In this study, we investigated whether end-to-side (ETS) neurorrhaphy, which is an axonal provider, could be useful as an SC provider to support axonal elongation in ANGs. We found that ETS neurorrhaphy effectively promoted SC migration into ANGs when an epineurium window combined with partial neurectomy was performed, and the effectiveness increased when it was applied bilaterally. When we transplanted ANGs containing migrated SCs via ETS neurorrhaphy (hybrid ANGs) to the nerve gap, hybrid ANGs increased the number of regenerated axons and facilitated rapid axonal elongation, particularly when ETS neurorrhaphy was applied to both edges of the graft. This approach may represent a novel application of ETS neurorrhaphy and lead to the development of hybrid ANGs, making ANGs more practical in a clinical setting.

Highlights

Nerve autograft has been a standard treatment option for reconstructing peripheral nerve injuries or defects; it is associated with a limited supply of the donor nerve and the elimination of the donor nerve function [1, 2]
We demonstrated the relationship between axonal regeneration and migration of Schwann cells (SCs) through ANGs utilizing transgenic mice expressing fluorescence in SCs and axons, and a highly intimate interaction, described as a “dance,” exists between regenerating axons and proliferating migrated SCs [12, 13]
We previously reported the characteristics of SCs migration into the nerve allograft; host SCs could rapidly migrate into ANG from the proximal and distal anastomosis of the graft [31]

Summary

Introduction

Nerve autograft has been a standard treatment option for reconstructing peripheral nerve injuries or defects; it is associated with a limited supply of the donor nerve and the elimination of the donor nerve function [1, 2]. Identifying alternatives to the nerve autograft has been widely investigated, and multiple types of nerve conduits, including silicone tubes and synthetic biodegradable tubes, have been experimentally and clinically developed in the last few decades [3]. The clinical usage of silicone conduits has been limited to gaps which are less than 10 mm [3]. Absorbable conduits were limited to be less than 10 mm in a rat model [3,4,5] and within 28 mm for sensory nerves in a clinical setting [4, 6, 7]. Acellular nerve allografts (ANGs) have been demonstrated as promising substitutes for short nerve gaps [2, 7]. The clinical usage of ANGs provided superior results

Methods

Results

Conclusion