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In this study, we have assessed the regenerative potential of a novel decellularization protocol for human and rat nerves for repairing nerve resections, compared to the gold standard autograft.\u00a0A 15-mm gap in the sciatic nerve was repaired with decellularized rat allograft (DC-RA), decellularized human xenograft (DC-HX), or fresh autograft (AG). Electrophysiology tests were performed monthly to evaluate muscle reinnervation, whereas histological and immunohistochemical analyses of the grafts were evaluated at 4\u00a0months. A short-term study was also performed to compare the differences between the two decellularized grafts (DC-RA and DC-HX) in early phases of regeneration.\u00a0The decellularization process eliminated cellularity while preserving the ECM and endoneurial tubules of both rat and human nerves. Higher amount of reinnervation was observed in the AG group compared to the DC-RA group, while only half of the animals of the DC-HX showed distal muscle reinnervation. The density of myelinated axons was significantly higher in AG compared to both DC grafts, being this density significantly higher in DC-RA than in DC-HX. At short term, fibroblasts repopulated the DC-RA graft, supporting regenerated axons, whereas an important fibrotic reaction was observed around DC-HX grafts.\u00a0In conclusion,\u00a0the decellularized allograft sustained regeneration through a long gap in the rat although at a slower rate compared to the ideal autograft, whereas regeneration was limited or even failed when using a decellularized xenograft.<\/jats:p>","DOI":"10.1007\/s00441-022-03682-1","type":"journal-article","created":{"date-parts":[[2022,9,17]],"date-time":"2022-09-17T00:02:31Z","timestamp":1663372951000},"page":"355-366","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["A novel decellularized nerve graft for repairing peripheral nerve long gap injury in the rat"],"prefix":"10.1007","volume":"390","author":[{"given":"Estefan\u00eda","family":"Contreras","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Bol\u00edvar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N\u00faria","family":"Nieto-Nicolau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar","family":"Fari\u00f1as","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patr\u00edcia","family":"L\u00f3pez-Chic\u00f3n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Navarro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1954-8562","authenticated-orcid":false,"given":"Esther","family":"Udina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,9,17]]},"reference":[{"key":"3682_CR1","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1016\/j.expneurol.2013.12.020","volume":"253","author":"A Al\u00e9","year":"2014","unstructured":"Al\u00e9 A, Bruna J, Morell M, van de Velde H, Monbaliu J, Navarro X, Udina E (2014) Treatment with anti-TNF alpha protects against the neuropathy induced by the proteasome inhibitor bortezomib in a mouse model. 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