{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:37:16Z","timestamp":1787027836512,"version":"build-2736575974"},"reference-count":234,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T00:00:00Z","timestamp":1764720000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["2011143"],"award-info":[{"award-number":["2011143"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Australian Government Research Training Programme Scholarship"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Cochlear implants are highly successful in restoring speech perception but variability in outcomes exists. Post-surgical fibrosis and neo-ossification are thought to play a significant role, being linked to increased impedance and loss of residual hearing and posing challenges for re-implantation. Hence, there is growing interest in pharmacological interventions to limit intracochlear fibrosis and neo-ossification. While current approaches focus on steroids, studies in other organs have identified many candidate drugs. However, selection is hindered by a limited understanding of the molecular and cellular mechanisms driving fibrosis after implantation. This review introduces potential drug candidates for cochlear implant-induced fibrosis, with many targeting core fibrotic pathways such as TGF-\u03b2\/SMAD, PDGF, and Wnt\/\u03b2-catenin or inhibiting pro-inflammatory signalling. By drawing on lessons from other tissues, this review identifies mechanisms and therapeutic approaches adaptable to the cochlea. Understanding fibrosis across organs will guide strategies to prevent or reverse cochlear fibrosis. Their translation requires careful evaluation of local delivery, minimal ototoxicity, and effects on the electrode\u2013tissue interface.<\/jats:p>","DOI":"10.3390\/cells14231924","type":"journal-article","created":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T16:47:37Z","timestamp":1764780457000},"page":"1924","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Understanding the Mechanisms Driving Fibrosis Following Cochlear Implantation\u2014Lessons from Other Tissues"],"prefix":"10.3390","volume":"14","author":[{"given":"Cecilia M.","family":"Pr\u00eale","sequence":"first","affiliation":[{"name":"School of Medical, Molecular and Forensic Sciences, Murdoch University, Murdoch, WA 6150, Australia"},{"name":"Institute for Respiratory Health, The University of Western Australia, Nedlands, Perth, WA 6009, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1076-5843","authenticated-orcid":false,"given":"Kady J.","family":"Braack","sequence":"additional","affiliation":[{"name":"Institute for Respiratory Health, The University of Western Australia, Nedlands, Perth, WA 6009, Australia"},{"name":"School of Human Sciences, The University of Western Australia, Crawley, Perth, WA 6009, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus","family":"Atlas","sequence":"additional","affiliation":[{"name":"Ear Science Institute Australia, Nedlands, Perth, WA 6009, Australia"},{"name":"Centre for Ear Sciences, Medical School, The University of Western Australia, Nedlands, Perth, WA 6009, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jafri","family":"Kuthubutheen","sequence":"additional","affiliation":[{"name":"Division of Surgery, Medical School, The University of Western Australia, Nedlands, Perth, WA 6009, Australia"},{"name":"Department of Otolaryngology Head and Neck Surgery, Sir Charles Gairdner Hospital, Perth, WA 6009, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tylah","family":"Miles","sequence":"additional","affiliation":[{"name":"Institute for Respiratory Health, The University of Western Australia, Nedlands, Perth, WA 6009, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8721-7357","authenticated-orcid":false,"given":"Wilhelmina H. A. M.","family":"Mulders","sequence":"additional","affiliation":[{"name":"School of Human Sciences, The University of Western Australia, Crawley, Perth, WA 6009, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2615-8338","authenticated-orcid":false,"given":"Steven E.","family":"Mutsaers","sequence":"additional","affiliation":[{"name":"Institute for Respiratory Health, The University of Western Australia, Nedlands, Perth, WA 6009, Australia"},{"name":"Pharmacology and Toxicology, School of Biomedical Sciences, Nedlands, Perth, WA 6009, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1001\/jamaoto.2013.293","article-title":"The early history of the cochlear implant: A retrospective","volume":"139","author":"Mudry","year":"2013","journal-title":"JAMA Otolaryngol. 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