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Recent evidence suggests that the voltage\u2010gated sodium channel Nav1.7, encoded by\n                    <jats:italic>Scn9a<\/jats:italic>\n                    , links nociceptive signaling with chondrocyte metabolic regulation. Here, we developed an acid\u2010responsive, cartilage\u2010targeted delivery system based on WYRGRL peptide\u2010modified chondroitin sulfate\/oxidized hyaluronan composite microspheres loaded with carbamazepine (CBZ), termed CBZ\/WCOM, for sustained intra\u2010articular CBZ delivery. In interleukin\u20101\u03b2 (IL\u20101\u03b2)\u2013challenged chondrocytes, CBZ\/WCOM attenuated inflammatory and catabolic responses, as indicated by\u00a0reduced\n                    <jats:italic>Ptgs2<\/jats:italic>\n                    ,\n                    <jats:italic>Mmp13<\/jats:italic>\n                    , and\n                    <jats:italic>Adamts5<\/jats:italic>\n                    expression, while partially restoring anabolic markers including\n                    <jats:italic>Col2a1<\/jats:italic>\n                    and\n                    <jats:italic>Acan<\/jats:italic>\n                    . Mechanistically, CBZ\/WCOM reduced sodium current density, modulated Na\u207a\/Ca\u00b2\u207a exchanger (NCX)\u2010associated Ca\n                    <jats:sup>2<\/jats:sup>\n                    <jats:sup>+<\/jats:sup>\n                    dynamics, and increased heat shock protein 70 (HSP70)\u00a0and Midkine secretion, supporting the involvement of Nav1.7\u2010related sodium channel signaling in chondrocyte regulation. In a mouse destabilization of the medial meniscus (DMM) model, intra\u2010articular CBZ\/WCOM improved mechanical withdrawal thresholds, reduced pain\u2010related neural remodeling, decreased osteophyte formation, partially preserved joint\u2010space width, improved cartilage matrix phenotype, and ameliorated subchondral bone alterations. By integrating WYRGRL\u2010mediated type II collagen (COL2) targeting with pH\u2010triggered CBZ release, CBZ\/WCOM supports lesion\u2010localized drug retention and provides a minimally invasive strategy for local OA therapy.\n                  <\/jats:p>","DOI":"10.1002\/advs.75986","type":"journal-article","created":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T07:34:40Z","timestamp":1780558480000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Lesion Site\u2010Targeted Microspheres Modulate Nav1.7\u2010Related Signaling for Osteoarthritis Treatment"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-6253-7168","authenticated-orcid":false,"given":"Cheng","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Orthopedic Surgery The Affiliated Yixing Hospital of Jiangsu University  Wuxi Jiangsu China"},{"name":"Medical 3D Printing Center Orthopedic Institute Department of Orthopedic Surgery The First Affiliated Hospital School of Basic Medical Sciences Interdisciplinary Innovation Center for Nanomedicine MOE Key Laboratory of Geriatric Diseases and Immunology Changzhou Geriatric Hospital Suzhou Medical College Biomedical Basic Research Center of Jiangsu Soochow University  Suzhou Jiangsu China"},{"name":"Regenerative Medicine &amp; Tissue Engineering Research Center Institute of Medical Innovation and Translation The Affiliated Yixing Hospital of Jiangsu University  Yixing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1930-7403","authenticated-orcid":false,"given":"Jiaying","family":"Li","sequence":"additional","affiliation":[{"name":"Medical 3D Printing Center Orthopedic Institute Department of Orthopedic Surgery The First Affiliated Hospital School of Basic Medical Sciences Interdisciplinary Innovation Center for Nanomedicine MOE Key Laboratory of Geriatric Diseases and Immunology Changzhou Geriatric Hospital Suzhou Medical College Biomedical Basic Research Center of Jiangsu Soochow University  Suzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinjin","family":"Ma","sequence":"additional","affiliation":[{"name":"Medical 3D Printing Center Orthopedic Institute Department of Orthopedic Surgery The First Affiliated Hospital School of Basic Medical Sciences Interdisciplinary Innovation Center for Nanomedicine MOE Key Laboratory of Geriatric Diseases and Immunology Changzhou Geriatric Hospital Suzhou Medical College Biomedical Basic Research Center of Jiangsu Soochow University  Suzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaonan","family":"Yuan","sequence":"additional","affiliation":[{"name":"Medical 3D Printing Center Orthopedic Institute Department of Orthopedic Surgery The First Affiliated Hospital School of Basic Medical Sciences Interdisciplinary Innovation Center for 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