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Recent studies have shown that the excessive unbalanced activation of Wnt\/\u03b2\u2010catenin signaling is connected with the pathogenesis of TMJOA and due to the inability to inhibit the over\u2010activated Wnt pathway, while Wnt16\u2010deficient mice has a more severe Knee OA. However, the efficacy of direct intra\u2010TMJ injection of Wnt16 for the relief of TMJOA is still not directly confirmed. Moreover, small\u2010molecule drugs such as Wnt16 usually exhibit short\u2010lived efficacy and poor treatment adherence. Therefore, in order to obtain a stable release of Wnt16 both in the short and long term, this study fabricates a double\u2010layer slow\u2010release Wnt16 carrier based on mesoporous silica nanospheres (MSNs) encased within hyaluronic acid (HA) hydrogels. The biofunctional hydrogel HA\/Wnt16@MSN is analyzed both in vitro and in vivo to evaluate the treatment of TMJOA. As a result, it shows superior pro\u2010cartilage matrix restoration and inhibition of osteoclastogenesis ability, and effectively inhibits the over\u2010activation of the Wnt\/\u03b2\u2010catenin pathway. Taken together, biofunctional hydrogel HA\/Wnt16@MSN is a promising candidate for the treatment of TMJOA.<\/jats:p>","DOI":"10.1002\/advs.202404396","type":"journal-article","created":{"date-parts":[[2024,9,9]],"date-time":"2024-09-09T08:01:58Z","timestamp":1725868918000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Microgel Encapsulated Mesoporous Silica Nanoparticles for Releasing Wnt16 to Synergistically Treat Temporomandibular Joint Osteoarthritis"],"prefix":"10.1002","volume":"11","author":[{"given":"Yan","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Oral Surgery Shanghai Ninth People's Hospital College of Stomatology Shanghai Jiao tong University School of medicine National Clinical Research Center for Oral Diseases Shanghai Key Laboratory of Stomatology Shanghai Research Institute of Stomatology Research Unit of Oral and Maxillofacial Regenerative Medicine, Chinese Academy of 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