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To address these limitations, we previously developed a small\u2010gap chitosan\u2010based conduit that provides a controlled microenvironment for regenerative interventions. This study aimed to investigate whether SOX5 overexpression enhances Schwann cell regenerative potential and, when combined with this conduit, synergistically promotes peripheral nerve regeneration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Schwann cells were transduced with SOX5 lentivirus and assessed for proliferation, migration, and neurotrophic factor secretion in\u00a0vitro. In a rat sciatic nerve transection model (2\u2010mm gap), animals received a chitosan conduit with intraluminal injection of SOX5 lentivirus. Histological, electrophysiological, and behavioral assessments were conducted at 12\u2009weeks post\u2010surgery.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>SOX5 overexpression significantly enhanced Schwann cell proliferation, migration, and secretion of BDNF, NGF, CNTF, and VEGF, while maintaining the dedifferentiated repair phenotype. In\u00a0vivo, the combination of SOX5 lentivirus and chitosan conduit improved axonal regeneration, reduced muscle atrophy, and increased conduction velocity and locomotor recovery relative to the empty conduit group.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>Lentivirus\u2010mediated SOX5 overexpression drives Schwann cells toward a repair phenotype and, when integrated with a small\u2010gap chitosan\u2010based conduit, effectively promotes structural and functional nerve regeneration.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jns.70120","type":"journal-article","created":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T05:46:51Z","timestamp":1774331211000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["<scp>SOX5<\/scp>\n                    Overexpression in Schwann Cell Combined With Chitosan\u2010Based Conduit Promotes Peripheral Nerve Regeneration"],"prefix":"10.1111","volume":"31","author":[{"given":"Bo","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Orthopedics and Trauma Peking University People's Hospital  Beijing China"},{"name":"Key Laboratory of Trauma and Neural Regeneration Peking University  Beijing China"},{"name":"National Center for Trauma Medicine  Beijing China"},{"name":"Beijing Laboratory of Trauma and Nerve Regeneration  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengshi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics and Trauma Peking University People's Hospital  Beijing China"},{"name":"Department of Cardiac Surgery Beijing Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junyu","family":"Su","sequence":"additional","affiliation":[{"name":"Shenzhen University Medical School Shenzhen University  Shenzhen China"},{"name":"Department of Teaching and Research Shenzhen University General Hospital  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baixin","family":"Gu","sequence":"additional","affiliation":[{"name":"Shenzhen University Medical School Shenzhen University  Shenzhen China"},{"name":"Department of Teaching and Research Shenzhen University General Hospital  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingxin","family":"Duan","sequence":"additional","affiliation":[{"name":"Shenzhen University Medical School Shenzhen University  Shenzhen China"},{"name":"Department of Teaching and Research Shenzhen University General Hospital  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shenzhen University Medical School Shenzhen University  Shenzhen China"},{"name":"Department of Teaching and Research 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