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 Medical Sciences, Shanghai, 200011, China.
National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Engineering Research Center of Advanced Dental Technology and Materials, Shanghai, 200011, China.
Adv Sci (Weinh). 2024 Nov;11(41):e2404396. doi: 10.1002/advs.202404396. Epub 2024 Sep 9.
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.
颞下颌关节骨关节炎（TMJOA）是口腔颌面外科中常见的退行性关节疾病。最近的研究表明，Wnt/β-连环蛋白信号通路的过度失衡激活与 TMJOA 的发病机制有关，由于无法抑制过度激活的 Wnt 通路，而 Wnt16 缺陷型小鼠的膝骨关节炎更严重。然而，直接向 TMJ 内注射 Wnt16 缓解 TMJOA 的疗效尚未直接得到证实。此外，Wnt16 等小分子药物通常表现出疗效短暂和治疗依从性差的问题。因此，为了在短期和长期内获得 Wnt16 的稳定释放，本研究基于介孔硅纳米球（MSNs）构建了一种双层缓释 Wnt16 载体，并封装在透明质酸（HA）水凝胶中。对生物功能水凝胶 HA/Wnt16@MSN 进行了体外和体内分析，以评估其对 TMJOA 的治疗效果。结果表明，它具有优越的促进软骨基质修复和抑制破骨细胞生成能力，并能有效抑制 Wnt/β-连环蛋白通路的过度激活。综上所述，生物功能水凝胶 HA/Wnt16@MSN 是治疗 TMJOA 的一种有前途的候选药物。
