携载BMP-2的PLGA缓释微球的制备及其成骨活性的研究  

Study on preparation and osteogenic effects of BMP-2-loaded PLGA microspheres with a sustained control release

作　　者：吴永恒[1] 张孜君[1] 黄岩[1] 赵文[1] 

机构地区：[1]北京航天总医院骨科,北京100076

出　　处：《中国医药导报》2017年第23期25-28,共4页China Medical Herald

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,正态分布,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。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-2-1oaded 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-2-1oaded microspheres on the proliferation and differentiation of bone marrow mesenchymal stem cells （BMSCs） in vitro and the ectopic bone for- mation inside the mouse thigh muscle were studied. Results The average size of PLGA particles loaded with BMP-2 was （242.2＋31.3） gm with smooth surface. BMP-2 released from microspheres displayed a biphasic release profile. BMSCs cultured with BMP-2-1oaded 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-2-1oaded-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, which can promote the proliferation and differentiation of BM- SCs in vitro and ectopic bone formation in vivo. BMP-2-1oaded PLGA microsphere holds high potential for wide appli- cation in bone tissue regeneration.

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 

分 类 号：R687.3[医药卫生—骨科学]