NANOZR种植体表面ZIF-8/ZA载药涂层促进骨质疏松状态下骨结合的作用及机制研究

氧化锆种植体的美观性好且不利于菌斑附着，是目前研究的热点，但其在骨质疏松领域的研究仍不足。骨质疏松状态下种植体骨结合强度差，愈合时间长，成功率低是亟待解决的问题。在种植体表面制备唑来膦酸(ZA)涂层可改善种植体骨结合，但药物的长效缓释仍是难点，其关键在于选择合适的载体并构建药物缓释系统。沸石咪唑酯骨架-8(ZIF-8)有三级药物缓释特性，用其负载ZA能长效缓释Zn2+和ZA。因此，本项目拟在氧化钇和氧化铈稳定四方晶氧化锆(NANOZR)种植体表面制备ZIF-8/ZA载药缓释涂层，将阐明ZIF-8/ZA载药涂层NANOZR种植体促进成骨细胞分化和抑制破骨细胞分化的双重作用，探索其通过Zn2+的缓释调节MAPK/Akt信号通路促进成骨和通过ZA的缓释调节RANK/RANKL/OPG信号通路抑制破骨的机制猜想，为改善骨质疏松状态下种植体骨结合强度，缩短愈合时间，提高成功率提供创新思路和实验基础。

Zirconia has been increasingly used in implant dentistry due to its aesthetic performance as well as excellent mechanical properties and biocompatibility. Zirconia implant has also shown to inhibit bacterial adhesion and biofilm formation on its surface. However, few studies have investigated the application of zirconia implant in the field of osteoporosis. Osteoporosis seriously affects the osseointegration, healing time and clinical success rate of the dental implant. Preparation of zoledronic acid (ZA) coating on the implant surface can improve implant osseointegration. However, the sustained long-term release of ZA is still an unsolved problem. Selecting an appropriate carrier to load ZA and constructing a drug sustained-release system are supposed to be an effective method. Imidazolate framework-8 (ZIF-8) has excellent biocompatibility, biodegradability, and sustained drug-controlled release property to load ZA. And the ZIF-8/ZA drug delivery system can obtain highly efficient loading and sustained release of Zn2+ and ZA. Therefore, this project intends to prepare ZIF-8/ZA drug delivery coatings on the surface of the NANOZR implant. We will clarify its role in promoting osteoblast differentiation and inhibiting osteoclast differentiation. Then we will explore its mechanism of promoting osteogenesis through the sustained release of Zn2+ and ZA to respectively regulate the MAPK/Akt signaling pathway and RANK/RANKL/OPG signaling pathway. We believe our study will lay the foundation and provide a theoretical basis for the implantation treatment in osteoporotic conditions.