微小RNA促进钛合金植入体骨整合的界面骨代谢研究

Due to the long healing period, poor bone/implant integration, high incidence rate of loosening, displacement and complication, patients with osteoporosis’s fracture has a higher mortality. Therefore, how to promote bone healing and improve the bone/implant bonding strength are two main problems to the patients with osteoporosis’s fracture. On the basis of our previous studieswith miRNA-21, this project aims at promoting the new bone remodeling of interface between implant and bone tissue and regulating the imbalance of osteoblast-osteoclast by optimizing the miRNAs and their combinations. Furthermore, this study will propose new theories at the molecular level for the treatment of osteoporosis’s fracture. Relying on the nanocapsules technique, this project will build a delivery-transfection system and a surface functionalized titanium implants which are suitable for clinical transformation. This study will provide a new strategy for the treatment of osteoporotic fracture.

钛合金植入物固定骨质疏松骨折是目前最常用的治疗手段，但老年骨质疏松患者骨折愈合周期长，植入体骨整合性差，松动、移位或下沉的发生率高，患者长期卧床并发症多、致死率高，促进骨折快速愈合和提高植入体骨整合强度是骨质疏松骨折面临的两大难题。本课题在miRNA-21促进骨愈合和钛合金骨整合的前期工作基础上优选其他miRNAs及其组合，希望解决骨质疏松骨折骨后植入体与骨的界面新骨代谢慢和成骨-破骨耦联失衡问题，促进骨质疏松骨折愈合，提高植入体的骨整合强度；从分子水平研究骨质疏松骨折治疗的新方法，探讨骨整合界面的骨代谢机制。课题以miRNA纳米微囊技术为基础，将miRNA活化基质与钛合金表面改性相结合，构建适合临床转化的miRNA投递和转染体系和功能化钛合金植入体，为骨质疏松骨折治疗提供新技术。

钛合金植入体具有生物惰性，通常导致种植后骨整合不良(临床上称为“松动”现象)，最终导致手术成功率不理想。而理想的种植体必须具有有利于成骨细胞粘附、扩散、增殖和分化的表面。因此，对钛进行表面改性以提高表面生物活性，最终满足临床需求仍是当前研究的重点。本课题利用miRNA-21在转录后水平调控基因表达，促进骨骼发育的重要作用，研究了骨质疏松骨折骨后植入体与骨的界面新骨代谢慢和成骨-破骨耦联失衡问题，实现了miRNA-21及合成物对骨质疏松骨折愈合，提高了植入体的骨整合强度；从分子水平研究了骨质疏松骨折治疗的新方法并对骨整合界面的骨代谢机制进行了探讨。课题以miRNA纳米微囊技术为基础，将miRNA活化基质与钛合金表面改性相结合，构建了miRNA投递和转染体系和功能化钛合金植入体，后期将针对骨质疏松骨折探讨适合临床转化的新工艺。