Noncellular modification of Acellular Nerve Allografts for peripheral nerve reconstruction: A systematic critical review of the animal literature

Filippo Boriani, Nicola Fazio, Federico Bolognesi, Francesca Alice Pedrini, Claudio Marchetti, Nicola Baldini

Research output: Contribution to journalReview articlepeer-review


Acellular Nerve Allografts (ANAs) have established as a promising alternative to the autologous nerve grafts, which currently represent the gold-standard yet. This research group has recently systematically reviewed the cell-based enriching methods described in the literature for recellularization of ANAs. The effect of recellularization is a consistent improvement of peripheral neuroregeneration compared to plain ANAs. The aim of this study was to systematically review the effects on nerve regeneration when ANAs enrichment is obtained through biological/chemical and physical modification instead of cells. Pubmed, ScienceDirect, Medline and Scopus databases were searched for articles on noncellular modification of ANAs, published between since January 2007 and December 2017. Inclusion criteria were English language, contents on noncellular enrichment of ANAs in peripheral nerve regeneration, in vivo study design and post-grafting neuroregenerative outcome assessment. Exclusion criteria were central nervous system as the site of ANAs application, nerve conduits, xenografts, case series, case reports and reviews. Only animal studies were found eligible. Sixteen papers were included and analyzed categorized with regard to animal model, decellularization method, graft-enriching mode and neuroregenerative tests performed. Noncellular-based stimulation of ANAs demonstrated positive effects on recovery of nerve function, when compared with nerve grafting depending on plain basic ANAs. The neuroregenerative effect of autografting still appears superior to ANAs, even with noncellular enrichment of ANAs. However this literature review showed that in e few studies modified ANAs closely approached or even overperformed autografts. Future research should include more preclinical investigations on this promising tool as well as clinical translation, in order to increase the level of evidence available on the challenging field of peripheral nerve reconstruction.

Original languageEnglish
Pages (from-to)692-703
Number of pages14
JournalWorld Neurosurgery
Publication statusE-pub ahead of print - Nov 7 2018


  • peripheral nerve reconstruction
  • acellular nerve allograft
  • schwann cell
  • stem cell
  • noncellular enhancement
  • nerve regeneration
  • systematic review


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