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Gene therapy has emerged as a promising strategy for cartilage regeneration, particularly through the use of functional RNA and biomaterial\u2010assisted frameworks. In this study, an innovative gene\u2010activated self\u2010healing hydrogel is developed and fabricated for the controlled release of miR140\u20105p, a key regulator of cartilage regeneration. The hydrogel, crosslinked via UV radiation, is composed of aminated hyaluronic acid and a modified photosensitizer (NB). To enhance the scaffold's structural integrity and gene delivery efficiency, mineralized silk fibroin and miR140\u20105p\u2010loaded MON\u2010PEI nanoparticles are incorporated. These findings demonstrate that this novel hydrogel (miR140\u20105p\u2010CaP@mSF\u2010HA\u2010NB) effectively encapsulates and releases miR140\u20105p, exhibits excellent biocompatibility, and promotes enhanced cartilage regeneration in both in vitro and in vivo models. Therefore, this gene\u2010activated hydrogel holds significant potential for clinical applications in the treatment of articular cartilage defects.<\/jats:p>","DOI":"10.1002\/advs.202406479","type":"journal-article","created":{"date-parts":[[2024,11,5]],"date-time":"2024-11-05T08:03:58Z","timestamp":1730793838000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Self\u2010Healing Hyaluronic Acid\u2010based Hydrogel with miRNA140\u20105p Loaded MON\u2010PEI Nanoparticles for Chondrocyte Regeneration: Schiff Base Self\u2010Assembly Approach"],"prefix":"10.1002","volume":"12","author":[{"given":"Wei","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Orthopedics State Key Laboratory of Complex Severe and Rare Diseases Peking Union Medical College Hospital Chinese Academy of Medical Sciences &amp; Peking Union Medical College  Beijing 100730 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5888-8805","authenticated-orcid":false,"given":"Han","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics State Key Laboratory of Complex Severe and Rare Diseases Peking Union Medical College Hospital Chinese Academy of Medical Sciences &amp; 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