磷酸钙骨水泥(CPC)是生物安全性好，可载药缓释，可注射成型的多能骨修复材料，但降解缓慢、降解不完全，效果欠佳。将CPC与乳酸-羟基乙酸共聚物(PLGA)微球复合后,其降解成骨性能得到改善，除了PLGA微球水解后在CPC内部形成孔隙网络，有利局部营养作用的原因外，我们前期工作发现可能还与破骨细胞优先对CPC机体中的PLGA进行识别、吸收后，引发破骨细胞与成骨细胞的偶联活动加强有关，类似天然骨代谢过程，其机理有待阐明。本研究据此假设：破骨细胞也是植入材料降解成骨的关键因素，如在材料内部先增强破骨细胞活动，可达到促进CPC的降解成骨作用。研究拟用促破骨细胞分化相关基因修饰骨髓间充质干细胞(BMSCs)，根据体外实验结果选择最优基因修饰方案后，进一步将基因修饰的BMSCs进行微囊包裹，作为活性致孔剂和CPC复合，利用细胞、动物实验观察其降解、成骨性能，为促进CPC的降解成骨研究提供新的思路。

Calcium Phosphate Cement(CPC) is an injectable bone substitute scaffolds materials, despite its advantages such as capable of minimally invasive,sustainable delivery of loaded drug, and growth factors, the clinical application is still limited due to the slow degradation of the materials. Our previous studies have shown that CPC matric mixied with poly(lacticco-glycolic acid)(PLGA) microspheres is an effective way to promote its degradation and osteogenesis. Beside the reason related to the degradation of the PLGA microspheres leaded to a porous struction created, which wll in favor of the ingrowth of osteogenic activity related cells migration, exchange of nutritive materials, the activeties of osteoclast affiliated to PLGA microspheres seem plays an important role which have Not been well clarified. We discovered that the degradation of PLGA up-regulated expression of RANK mRNA in monocyte-derived macrophage and therefore hypothesized that the activating of osteoclasts is the primary step for the promotion of CPC absorption and osteogenesis, by increasing the proportion of endogenous RANKL, sustainable activation of osteoclast will achieve and the material degradation will be promoted. The purpose of the study is to genetically modified bone mesenchymal stem cells(BMSCs) by using either gene transfection technique or RNA interference(RNAi) technology, subsequently, the genetic modified BMSCs will be encapsulted with alginate beads and embed with CPC matric, the in vitro and in vivo experiments will be performed to investigate the impact to the degradation and osteogenesis of CPC.