吴永恒++++++张孜君++++++黄岩++++++赵文

    [摘要] 目的 以聚乳酸-聚乙醇酸(PLGA)制备新型缓释载药微球，携载骨生长因子2(BMP-2)，研究其物理学特性以及在体内、体外对成骨的影响。 方法 采用复合复乳法制备载有BMP-2的PLGA缓释微球，检测形态、粒径、载药率、包封率、释药规律。观察其在体外环境下对骨髓间充质干细胞(BMSCs)增殖分化的影响，观察其在小鼠股部肌肉内异位成骨的情况。 结果 缓释微球的表面光滑，平均粒径为(242.2±31.3)μm，正態分布，微球的体外释药规律符合双相动力学释药规律。随着微球缓释量的增加，携载BMP-2的微球组细胞增殖明显加快(P < 0.05)，BMP-2介导的BMSCs增殖呈浓度依赖性升高(P < 0.05)。微球体内成骨效果明显，4周后可见大量的骨小梁，并有骨髓腔形成。 结论 携载BMP-2的PLGA缓释微球具有良好的载药特性，可明显促进BMSCs增殖、分化、提高成骨活性。在骨组织工程研究中具有广阔的应用前景。

    [关键词] 聚乳酸-聚乙醇酸；人骨形成蛋白；微球载体；成骨活性；骨组织工程

    [中图分类号] R687.3 [文献标识码] A [文章编号] 1673-7210(2017)08(b)-0025-04

    [Abstract] Objective To research the physical characteristics of novel bone morphogenetic factor-2 (BMP-2)-loaded poly (lactic-co-glycolic acid) (PLGA) microspheres with a sustained control release of BMP-2 for bone induction and the influence ossification in vitro and in vivo. Methods The BMP-2-loaded PLGA microspheres through double emulsion method was prepared， and the physiological properties of microspheres was investigated， including particle size and loading and encapsulation rates of BMP-2， and the release profile of BMP-2. The effects of BMP-2-loaded microspheres on the proliferation and differentiation of bone marrow mesenchymal stem cells (BMSCs) in vitro and the ectopic bone formation inside the mouse thigh muscle were studied. Results The average size of PLGA particles loaded with BMP-2 was (242.2±31.3) μm with smooth surface. BMP-2 released from microspheres displayed a biphasic release profile. BMSCs cultured with BMP-2-loaded microspheres showed the fastest proliferation rate among all groups (P < 0.05). The proliferation rate of BMSCs was dose-dependent on BMP-2 (P < 0.05). Ectopic bone formation in the mouse thigh muscle was observed after injection of BMP-2-loaded-microspheres. A large number of trabecular bone appeared with emerging bone marrow cavity 4 weeks after the injection. Conclusion The new method to prepare PLGA microspheres loaded with BMP-2 has a sustained control release rate ......