Noncellular Modification of Acellular Nerve Allografts for Peripheral Nerve Reconstruction: A Systematic Critical Review of the Animal Literature

Abstract

Background: Acellular nerve allografts (ANAs) have been established as promising alternatives to autologous nerve grafts, which represent the reference standard. Our research group recently performed a systematic review of reported cell-based-enriching methods for recellularization of ANAs. Recellularization results in consistent improvement of peripheral neuroregeneration compared with plain ANAs. We systematically reviewed the effects on nerve regeneration when ANA enrichment was obtained through biological, chemical, and physical modification instead of cells.

Methods: The PubMed, ScienceDirect, Medline, and Scopus databases were searched for reports of noncellular modification of ANAs, reported from January 2007 to December 2017. The inclusion criteria were English language, noncellular enrichment of ANAs in peripheral nerve regeneration, an in vivo study design, and postgrafting neuroregenerative outcomes assessment. The exclusion criteria were the central nervous system as the site of ANA application, nerve conduits, xenografts, case series, case reports, and reviews.

Results: Only animal studies were found to be eligible. We included 16 studies, which were analyzed regarding the animal model, decellularization method, graft-enriching mode, and neuroregenerative tests performed.

Conclusions: Noncellular-based stimulation of ANAs demonstrated positive effects on recovery of nerve function compared with nerve grafting compared with plain ANAs. The neuroregenerative effect of autografting still appeared superior to ANAs, even with noncellular enrichment of ANAs. However, we found that in a few studies, modified ANAs closely approached or even outperformed autografts. Future research should include more preclinical investigations of this promising tool and clinical translation to increase the level of evidence available in the challenging field of peripheral nerve reconstruction.

Keywords: Acellular nerve allograft; Nerve regeneration; Noncellular enhancement; Peripheral nerve reconstruction; Schwann cell; Stem cell; Systematic review.