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These grafts are characterized by their preservation of the native perineurial barrier architecture and a unique extracellular matrix (ECM) composition, distinct from the endoneurial basement membrane. This distinctive ECM profile endows ANPs with significantly enhanced barrier integrity and robust neuroprotective properties. In vitro evaluations confirmed that ANP provides a highly favorable substrate, effectively supporting the adhesion and active proliferation of dorsal root ganglion neurons. In a rat model of sciatic nerve transection, ANP grafts demonstrated remarkable therapeutic efficacy. They markedly inhibited the deposition of chondroitin sulfate proteoglycans (CSPGs) at the repair site, thereby preventing traumatic neuroma formation. Furthermore, ANP treatment resulted in a doubling of regenerated axon density and a significant increase in target muscle action potential amplitude. Behavioral recovery in ANP-treated animals approached the functional levels observed in crush-injury controls. Multiomics analyses provided mechanistic insight, revealing that ANP-mediated repair activates multiple pro-regenerative signaling pathways. These collective findings position ANP grafts as a highly promising and clinically translatable biomaterial strategy for improving functional outcomes in peripheral nerve repair.<\/jats:p>","DOI":"10.1093\/rb\/rbag047","type":"journal-article","created":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T12:44:13Z","timestamp":1772887453000},"source":"Crossref","is-referenced-by-count":1,"title":["Acellular nerve perineurium repairs peripheral nerve injuries in a rat model via ECM-mediated barrier and optimization of the regenerative microenvironment"],"prefix":"10.1093","volume":"13","author":[{"given":"Fulin","family":"He","sequence":"first","affiliation":[{"name":"Department of Orthopaedics, The Seventh Affiliated Hospital of Sun Yat-Sen University , Shenzhen 518107,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenpeng","family":"Li","sequence":"additional","affiliation":[{"name":"Orthopedic Center, Department of Orthopedics and Traumatology, The Affiliated Guangdong Second Provincial General Hospital of Jinan University , Guangzhou 510317,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fawei","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Microsurgery, Orthopedic Trauma and Hand Surgery, The First Affiliated Hospital, Sun Yat-sen University , Guangzhou 510080,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuihuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Microsurgery, Orthopedic Trauma and Hand Surgery, The First Affiliated Hospital, Sun Yat-sen University , Guangzhou 510080,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xijun","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Microsurgery, Orthopedic Trauma and Hand Surgery, The First Affiliated Hospital, Sun Yat-sen University , Guangzhou 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510080,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuo","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, The Eighth Affiliated Hospital, Sun Yat-sen University , Shenzhen 518033,","place":["China"]},{"name":"Biological Laboratory of Hetao Cooperation Zone, the Eighth Affiliated Hospital of Sun Yat-sen University , Shenzhen 518033,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingtang","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Microsurgery, Orthopedic Trauma and Hand Surgery, The First Affiliated Hospital, Sun Yat-sen University , Guangzhou 510080,","place":["China"]},{"name":"Guangdong Provincial Peripheral Nerve Tissue Engineering and Technology Research Center , Guangzhou 510080,","place":["China"]},{"name":"Guangdong Province Engineering Laboratory for Soft Tissue Biofabrication , Guangzhou 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