钛合金表面羟基磷灰石涂层负载微小RNA诱导成骨机制的研究

羟基磷灰石（HA）因其与骨相似的成份及良好的生物相容性，已被广泛用于钛合金骨科器械的表面改性。对于骨代谢失衡的骨质疏松骨折病人，需改善HA涂层的骨诱导性以促进骨折的愈合。目前对HA涂层的骨传导及诱导的研究多集中在观察蛋白的表达，但很少深层次关注对蛋白表达起调节作用的微小RNA（miRNA）。本项目针对与BMP/Smad和Wnt/β-catenin信号通路密切相关的miRNA，首先通过体外细胞实验明确HA涂层对相关miRNA表达的调节作用；在此基础上，以微流体技术筛选miRNA及其组合以期改善HA涂层的骨诱导性。基于上述结果，采用纳米微囊包覆技术将miRNA与HA涂层复合，通过调整涂层组成和微囊结构控制miRNA的响应性释放，进一步开展动物实验评价复合miRNA的HA涂层促进骨修复的效果，并针对前述信号通路阐明miRNA诱导成骨的作用机制。

Hydroxyapatite (HA) has been widely used for coating titanium alloy surface because of its similar mechanical properties to natural bone and good biocompatibility. Due to the unbalancing of bone formation and bone resoprtion in osteoporosis patients, it is necessary to improve the osteoinductivity of HA coating for promoting osteoporotic fracture healing. Most of studies on the osteoconductivity and osteoinductivity of HA is focusing on expression levels of some bone molecules, but little attention has been paid on micro-RNAs those regulating multiple signaling pathways within bone cells. In this project, the relationship between HA and miRNAs those regulating BMP/Smad and Wnt/β-catenin signaling pathways will be indentified. Furthermore, osteoinductivity of HA coating will be improved by optimizing the miRNAs and their combination with micro-fluid technology. Finally, the optimized miRNAs will be encapsulated in nanogel and loaded on HA coating. The miRNAs will be released by controlling the degradation rate of nanogel. The osteoinductivity of miRNAs combined with HA coating will be evaluated on osteoporotic rat model. The possible mechanism of miRNAs regulating BMP/Smad and Wnt/β-catenin signaling pathways will be explored.