基于抗钛-骨界面氧化应激效应的糖尿病人工种植体表面设计及骨整合研究

在糖尿病人种植治疗中，促进种植体骨整合是难点问题。研究表明种植体-骨界面氧化应激是干扰种植体与骨整合的关键因素，因此基于种植体-骨界面生物功能设计理念，种植体表面设计抗氧化应激功能膜层是促进糖尿病种植体骨整合的新手段。课题组前期已证实氧化铈纳米粒子（CNPs）具有抑制氧化应激诱导成骨细胞凋亡的作用，并且已在钛表面成功制备载CNPs微弧氧化复合功能膜层，为进一步验证钛表面微弧氧化实现CNPs抗氧化功能以促进糖尿病种植体骨整合的新设想，本项目拟采用体内外实验模型，系统评价CNPs对改善糖尿病致钛种植体骨整合率低的治疗效果，并利用microarray、多因子抗体芯片、通路抑制剂等分子生物学方法探索糖尿病状态下CNPs抑制氧化应激诱导成骨细胞损伤的分子信号通路，并揭示其可能的相互作用机制，为预防和降低糖尿病缺牙患者种植修复失败率、改善临床治疗效果提供实验基础和理论依据。

Dental implants have been widely used for the replacement of missing teeth in the clinic, but further improvements are needed to meet the clinical demands for faster and tighter osseointegration in healthy compromised patients. Clinical evidence indicates that diabetes is a major risk factor for titanium implant treatment with high failure rates and poor osteointegration. It is reported recently that oxidative stress and reactive oxygen species (ROS) overproduction may contribute to the impaired osteogenesis of porous titanium implants under diabetic conditions. Meanwhile, the cerium oxide nanoparticles (CNPs) are redox-active which have recently attracted attention for use in antioxidant therapy application. The micro-arc oxidation treatment of titanium (Ti) has attracted a great deal of attention. So in this study, we propose CNPs coatings may ameliorate the oxidative stress and the ROS overproduction, thus reverse the poor osseointegration under diabetic conditions, and investigate the underlying mechanisms. To test this hypothesis, both the in-vitro and in-vivo performance of CNPs-functionalized MAO Ti were investigated. The anticipated results are: the CNPs-functionalized MAO Ti could markedly ameliorate diabetes-induced impaired bioperformance of titanium via oxidative stress-mediated reactivation, which elicits a new surface functionalization strategy for better clinical performance of titanium implant in diabetic patients.