# Optimizing a feasible protocol for acellular nerve allografts: An experimental study

## TL;DR

This study shows that acellular nerve allografts can promote nerve regeneration in rats, offering a promising alternative to autografts for treating nerve injuries.

## Contribution

A feasible decellularization protocol for acellular nerve allografts is optimized and shown to avoid immune rejection in rats.

## Key findings

- Acellular nerve allografts supported axonal regeneration comparable to autografts in a 14-mm sciatic nerve defect.
- Fresh acellular allografts led to better muscle recovery and less atrophy than lyophilized grafts and autografts.
- Functional outcomes did not significantly differ between groups, despite differences in histomorphological recovery.

## Abstract

Peripheral nerve injuries often require surgical intervention when end-to-end coaptation is not feasible, with autologous nerve grafts being the current gold standard. However, limitations such as donor-site defects drive the search for alternative methods. This study explores the efficacy of acellular nerve allografts obtained through a feasible protocol as a potential off-the-shelf substitute for autografting in a 14-mm rat sciatic nerve defect. Thirty-two female Wistar rats were divided into four groups: autograft, lyophilized acellular allograft, fresh acellular allograft and silicone tube. Functional assessments and histological examinations were performed at 14 and 20 weeks post-surgery, respectively. Results showed comparable axonal regeneration between acellular nerve allografts and autografts. Histomorphometric analysis revealed no significant differences in axonal characteristics between groups. Muscle histomorphometry indicated superior recovery in animals treated with fresh acellular allografts, who exhibited the least muscle atrophy and larger muscle fiber diameter compared to lyophilized processed allografts and autografts. Functional assessments revealed no significant intergroup differences. Processed acellular allografts promote axonal regeneration similar to autografts in a 14-mm rat sciatic nerve defect. Fresh acellular allografts achieve better muscle reinnervation in the medial gastrocnemius muscle. However, axonal regeneration does not consistently correlate with functional or histomorphological outcomes of the hind leg muscle. The successful decellularization protocol and lack of immune rejection pave the way for adapting it to human nerve grafts. These could revolutionize clinical practice in our country, becoming an example of leveraging existing resources and replacing collagen conduits and autografts for treating certain injuries.