壳聚糖微球/小牛松质骨支架复合缓释体系的制备及体外生物活性评价  

Synthesis and in vitro characterization of chitosan microspheres/ceramic bovine bone composite scaffold

作　　者：李箐[1] 于欣[2] 周钢[2] 毋育伟[3] 胡洪成[3] 王彤[3] 唐志辉[1] LI Qing YU Xin ZHOU Gang WU Yu-wei HU Hong-eheng WANG Tong TANG Zhi-hui(Center of Digital Dentistry, Peking University School and Hospital of Stomatology ＆ National Engineering Laboratory for Digital and Material Technology of Stomatology ＆ Beijing Key Laboratory of Digital Stomatology, Beijing 100081, China School of Biological Science and Medical Engineering, Beihang University, Beijing 100191, China The Second Dental Center, Peking University School and Hospital of Stornatology, Beijing 100101, China)

机构地区：[1]北京大学口腔医学院·口腔医院,口腔医学数字化研究中心,口腔数字化医疗技术和材料国家工程实验室,口腔数字医学北京市重点实验室,北京100081 [2]北京航空航天大学生物与医学工程学院,北京100191 [3]北京大学口腔医学院·口腔医院第二门诊部,北京100101

出　　处：《北京大学学报（医学版）》2016年第6期1043-1048,共6页Journal of Peking University:Health Sciences

基　　金：首都市民健康项目(z2110005312001)资助~~

摘　　要：目的:通过乳液交联法合成壳聚糖微球并负载骨形态发生蛋白(bone morphogenetic protein-2,BMP-2),再将其复合于脱细胞基质的小牛松质骨支架,制备壳聚糖微球/小牛松质骨支架复合缓释体系。方法:使用红外光谱仪、扫描电镜对合成的复合缓释系统进行结构表征和形貌观察,并对微球的包封率和载药量进行检测。用动态浸泡的方法来检测BMP-2的体外释放特征,通过体外检测复合体系的细胞毒性和对细胞增殖的影响。结果:壳聚糖发生了交联并成功包载了BMP-2,微球平均直径为5.982μm,表面光滑,且成功负载于小牛松质骨支架,形成了新型的微球/支架药物缓释体系。缓释数据表明,5 mg微球在体外释放21 d,BMP-2逐渐释放,第21天时浓度仍达到(239.1±20.0)mg/L。体外测试表明,该缓释体系有利于小鼠前成骨细胞MC3T3-E1的生长,促进向成骨方向分化。结论:壳聚糖微球/小牛松质骨支架复合缓释体系实现了BMP-2的生物学功能及其在骨修复部位的持续、缓慢释放,为骨组织缺损的修复治疗及骨组织工程支架材料的选择提供了依据。Objective： The chitosan microspheres encapsulated with bone morphogenetic protein-2（ BMP-2） were prepared by the emulsion cross-linking method. Then the chitosan microspheres were loaded in the ceramic bovine bone（ CBB） to achieve the drug delivery system. Methods： The chemical structure and surface morphology of the drug delivery system were investigated by Fourier transform infrared spectroscopy（ FT-IR） and scanning electron microscope（ SEM） observation. Characterization preserved the loading capacity and encapsulation efficiency of the BMP-2. The dynamic immersion method was used to examine the in vitro release characteristic of BMP-2. Results： The chitosan microspheres were successfully encapsulated BMP-2 by cross-linking method. The microspheres were micron-sized（ 5. 982 μm） and spherical in shape with smooth surface morphology. From the release experiments,it was found that 5 mg chitosan / BMP-2 soaked for 21 days with a gradual release of BMP-2. The concentration of BMP-2 was（ 239. 1 ± 20. 0） mg / L on Day 21. The in vitro experiment showed that this novel drug delivery system could accelerate MC3T3-E1 cells proliferation and osteogenic differentiation. Conclusion： The drug delivery system achieves the biological function of BMP-2 and sustaining slow release in bone repair parts. Also it can provide the basis for repair of bone tissue defect treatment and the selection of bone tissue engineering scaffolds.

关 键 词：壳聚糖 微球体 药物释放系统 小牛松质骨 

分 类 号：R737.25[医药卫生—肿瘤]