Microgel Encapsulated Mesoporous Silica Nanoparticles for Releasing Wnt16 to Synergistically Treat Temporomandibular Joint Osteoarthritis

Abstract Temporomandibular joint osteoarthritis (TMJOA) is a commonly encountered degenerative joint disease in oral and maxillofacial surgery. Recent studies have shown that the excessive unbalanced activation of Wnt/β‐catenin signaling is connected with the pathogenesis of TMJOA and due to the inability to inhibit the over‐activated Wnt pathway, while Wnt16‐deficient mice has a more severe Knee OA. However, the efficacy of direct intra‐TMJ injection of Wnt16 for the relief of TMJOA is still not directly confirmed. Moreover, small‐molecule drugs such as Wnt16 usually exhibit short‐lived 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‐layer slow‐release 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‐cartilage matrix restoration and inhibition of osteoclastogenesis ability, and effectively inhibits the over‐activation of the Wnt/β‐catenin pathway. Taken together, biofunctional hydrogel HA/Wnt16@MSN is a promising candidate for the treatment of TMJOA.