巨噬细胞分为M1和M2两种表型，在骨重建时先由M1主导炎症反应清除损伤组织，然后极化为M2促进骨生成，此“炎症→骨生成”是维持骨组织稳态必不可少的过程。miR-223是此过程中巨噬细胞极化的主要调控者。骨内植物引起以M1为主的持续炎症反应，阻碍了M1向M2表型极化，使骨重建陷于停滞而至整合失败。传统采用的提高内植物整合方法的实质是减少巨噬细胞聚集，因局部缺乏“炎症→骨生成”过程而失败。本项目推测，如果调控巨噬细胞由M1向M2表型极化，引导炎症尽快过渡到修复阶段，即有可能增加局部骨生成，达到提高内植物-宿主骨整合的目的。据此，本项目首先制备HA-PEI/miR-223纳米递释系统，调控巨噬细胞向M2表型极化，然后采用山羊动物模型，观察内植物周围骨生成情况，探讨通过调控巨噬细胞表型提高内植物-宿主骨整合的可能性，从而为提高人工关节的长期稳定性、为修复假体周围骨缺损提供新思路和新方法。

Osteal macrophages can be classified into two phenotypes: M1 and M2. In bone remodeling, M1 dominant inflammation to eliminate the injured bone tissues. Then M1 polarizes to M2 phenotype to promote osteogenesis. This inflammation-osteogenesis processes is essential to bone homeostasis. miR-223 is a key regulator in macrophages phenotype polarization. The bone implants stimulate chronic inflammatory and fibrous response dominated by M1, preventing M2 polarization and bone formation. That may lead to bone remodeling arrest and failure of implant-host bone integration. The traditional methods to inhibit the inflammation fail to diminish macrophages accumulation, thus preventing inflammation-osteogenesis processes. We hypothesize that through regulating macrophages towards M2 polarization, the inflammation may be transit to osteogenesis process rapidly, hence promoting bone formation around implant and ultimately towards implant-host bone integration. The goat implant-bone models are used in this research, through HA-PEI/miR-223 nanodelivery system target regulation, to explore the possibility of implant-host bone integration enhancement by M2 polarization. This research could provide new method to enhance long term stability of prosthesis and improve bone defect reconstruction, as well as new theoretical basis for cellular immunology of bone implants.