活性氧簇在糖尿病致钛合金内植物失稳中的作用及机制研究

医用钛合金是目前临床使用最为广泛的骨植入材料，钛合金内植物失稳是其最常见和最严重的并发症，常导致治疗彻底失败。其中，糖尿病人钛合金内植物失败率高达10%-20%，远高于普通人群（1%-3%），说明其在"钛合金－骨"界面间存在某种导致内植物失稳的内源性因素。作为细胞内氧化酶代谢过程中的产物，活性氧簇（ROS）及氧化应激被证明是糖尿病致多种组织器官损害的重要机制。本课题组在前期工作中尝试将钛合金支架植入糖尿病兔模型的股骨髁缺损处，实验结果证实ROS导致成骨细胞功能受损及凋亡增加并阻碍新生骨向支架内的长入，提示ROS与糖尿病致钛合金内植物失稳相关。我们拟在此基础上开展深入研究，旨在进一步验证及阐明ROS在糖尿病致钛合金内植物失稳中的地位和作用，并探索其在"钛合金－骨"界面间的发生发展进程和作用机制，为揭示钛合金内植物失稳发病机理、预防和降低内植物失败率、改善临床治疗效果提供实验基础和理论依据。

Titanium (Ti)-based materials have been the most widely used biomaterials as bone substitutes for orthopedic and dental applications. However, the immediate and long-term implant stability is not satisfied with high rates of implant loosening or failure, especially under some disease conditions. Diabetes mellitus, a metabolic disease, has been proved to adversely affect the biological performance of Ti implants. The much higher failure rates of Ti implants in diabetic patients indicated that the destabilization of Ti implants may attribute to the tissue-affecting processes occurring at the implant-bone interface. Recent studies have shown that the hyperglycemia condition of diabetes could dramatically increase the level of reactive oxygen species (ROS) in both mitochondrial and cytoplasma, which may play a critical role in the pathophysiological procedure of diabetic organ damage. Our previous study found that the ROS overproduction under diabetic condition caused osteoblast dysfunction and cell apoptosis, and thus contributed to the impairment of bone healing with titanium implants, suggesting the relationship between ROS and destabilization of Ti implants. Based on these data, the present research will further investigate role of ROS in the diabetes-induced impaired osteointegration of Ti implants, the derivation and development of ROS on the implant-bone interface, and the underlying mechanism of ROS-mediated diabetes-induced Ti implant destabilization. An in depth understanding of how the ROS interacts with the implants may provide theoretical support and valuable adjunctive strategy in accelerating osteointegration of Ti and decreasing the implant failure, with great clinical potentials for bone defect treatment in diabetic and other systemic patients.