Tan Jia, Ren Ling, Xie Kai, Wang Lei, Jiang Wenbo, Guo Yu, Hao Yongqiang
Department of Orthopaedic Surgery, Shanghai Key Laboratory of Orthopaedic Implants, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
Clinical and Translational Research Center for 3D Printing Technology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
Regen Biomater. 2022 Nov 7;10:rbac092. doi: 10.1093/rb/rbac092. eCollection 2023.
Osteoporosis results in decreased bone mass and insufficient osteogenic function. Existing titanium alloy implants have insufficient osteoinductivity and delayed/incomplete fracture union can occur when used to treat osteoporotic fractures. Copper ions have good osteogenic activity, but their dose-dependent cytotoxicity limits their clinical use for bone implants. In this study, titanium alloy implants functionalized with a TiCu/TiCuN coating by arc ion plating achieved a controlled release of copper ions for 28 days. The coated alloy was co-cultured with bone marrow mesenchymal stem cells and showed excellent biocompatibility and osteoinductivity . A further exploration of the underlying mechanism by quantitative real-time polymerase chain reaction and western blotting revealed that the enhancement effects are related to the upregulation of genes and proteins (such as axin2, β-catenin, GSK-3β, p-GSK-3β, LEF1 and TCF1/TCF7) involved in the Wnt/β-catenin pathway. experiments showed that the TiCu/TiCuN coating significantly promoted osteoporotic fracture healing in a rat femur fracture model, and has good biocompatibility based on various staining results. Our study confirmed that TiCu/TiCuN-coated Ti promotes osteoporotic fracture healing associated with the Wnt pathway. Because the coating effectively accelerates the healing of osteoporotic fractures and improves bone quality, it has significant clinical application prospects.
骨质疏松症会导致骨量减少和成骨功能不足。现有的钛合金植入物骨诱导性不足,用于治疗骨质疏松性骨折时可能会出现骨折延迟愈合或不愈合。铜离子具有良好的成骨活性,但其剂量依赖性细胞毒性限制了其在骨植入物中的临床应用。在本研究中,通过电弧离子镀制备的TiCu/TiCuN涂层功能化钛合金植入物实现了铜离子28天的控释。涂层合金与骨髓间充质干细胞共培养,表现出优异的生物相容性和骨诱导性。通过定量实时聚合酶链反应和蛋白质免疫印迹法对其潜在机制进行进一步探索,结果显示,这种增强作用与Wnt/β-连环蛋白信号通路中相关基因和蛋白(如axin2、β-连环蛋白、GSK-3β、p-GSK-3β、LEF1和TCF1/TCF7)的上调有关。实验表明,在大鼠股骨骨折模型中,TiCu/TiCuN涂层显著促进了骨质疏松性骨折的愈合,并且基于各种染色结果显示具有良好的生物相容性。我们的研究证实,TiCu/TiCuN涂层的钛促进了与Wnt信号通路相关的骨质疏松性骨折愈合。由于该涂层有效加速了骨质疏松性骨折的愈合并改善了骨质量,因此具有显著的临床应用前景。