氧化应激是导致老龄人骨折愈合水平下降的主要原因。普遍认为其主要机制为氧化应激激活NF-κB诱导破骨细胞增加以及MSCs表观遗传失调。近来研究表明，氧化应激介导的材料与细胞间、细胞与细胞间功能失调，导致的血管生成能力下降可能是骨延迟愈合的关键，提示促进血管生成是潜在目标。前期研究中，我们发现氧化应激条件下，TiO2纳米管（TNT110）可诱导细胞抗氧化、利于细胞存活、分化以及细胞间相互调节。鉴于此，本项目拟探究氧化应激条件下，TNT110是否通过调节RAW264.7-HUVECs细胞交互，刺激HUVECs细胞膜表面受体及胞内与抗氧化、细胞凋亡及血管生成密切相关信号分子及下游蛋白的表达，进而实现促进血管生成。此外，通过构建老龄大鼠股骨植入模型，进一步验证TiO2纳米管对植入体周围血管生成的调控作用，提高对老龄性骨损伤修复机制的认知，为优化钛基植入体的设计和开发提供科学依据。

Oxidative stress in the bone tissue of elderly patients is the main reason leading to the decreased bone healing. In the oxidative stress microenvironment of bone tissue, osteoclast increase and MSCs epigenetic disorders induced by NF-κB activation are generally accepted mechanisms. Recent studies have shown that angiogenesis reduction caused by oxidative stress-mediated material-cell, cell-cell dysfunction after implantation may be the key to delayed bone healing, suggesting that angiogenesis is a potential target. In previous study, we identified that TiO2 nanotubes (TNT110) are able to induce cellular antioxidant activity, cell survival, differentiation, and cell interaction. In view of this, we will investigate whether TNT110 could promote angiogenesis under oxidative stress through RAW264.7-HUVECs cross-regulation as well as stimulate the cell membrane receptor of HUVECs, and further activate and regulate intracellular antioxidant, apoptosis and angiogenesis related molecules. We will further establish femoral implant model of aged rats, so as to verify the regulation effect of TiO2 nanotube on peripheral angiogenesis of implant under oxidative stress. This study is expected to deepen the understanding of the involved mechanism relevant to bone injury repair in elderly patients, and provide scientific basis for optimizing the design and development of titanium-based implants.