摘要
背景:采用生理盐水溶解重组人骨形态发生蛋白2/聚乳酸-聚乙醇酸共聚物微球时,活性成分易于吸收、流失,不能在局部维持较高浓度;而采用静脉血或骨髓血溶解时凝固时间难以掌握,往往在体外已凝血,失去可注射性,操作不便,因此还需一种能控制凝固时间的缓释载体。目的:制备携载重组人骨形态发生蛋白2的聚乳酸与聚乙醇酸缓释微球并将其与纤维蛋白胶复合,构建具有自固化能力的可注射性骨形态发生蛋白缓释体系。设计、时间及地点:对比观察实验,于2005-01/2008-04在解放军总医院骨科研究所完成。材料:聚乳酸-聚乙醇酸共聚物(聚乳酸/聚乙醇酸75/25,MW=3000,黏度0.025L/g)由山东省医疗器械研究所提供,重组人骨形态发生蛋白2由解放军军事医学科学院提供,纤维蛋白胶由杭州普济公司提供。方法:复乳-溶剂挥发法制备重组人骨形态发生蛋白2/聚乳酸-聚乙醇酸共聚物载药微球,然后将微球与纤维蛋白胶复合制备出重组人骨形态发生蛋白2/聚乳酸-聚乙醇酸共聚物/纤维蛋白胶复合材料。主要观察指标:复合材料凝固时间、体外释放性质、能谱分析及体外降解液pH值。结果:①与纤维蛋白胶相比,复合材料的固化时间少量增加。②复合材料的释放存在突释,2d骨形态发生蛋白释放量达到16.76%,42d释放量达到76.75%。③能谱分析显示微球混入纤维蛋白胶后优化了释放过程,延长了其释放时间。④复合材料的pH值变化介于微球与纤维蛋白胶之间。结论:重组人骨形态发生蛋白2/聚乳酸-聚乙醇酸共聚物/纤维蛋白胶复合材料具有良好的缓释效果并具有可注射性,既可以降低局部的酸环境,又可以在局部维持较高浓度,是具有良好应用前景的骨修复材料。
BACKGROUND：The active component in recombinant human bone morphogenetic protein-2/poly（lactide-co-glycolide） （rhBMP-2/PLGA） microsphere prone to be absorbed or lost during solution with physiological saline,and the setting time is uncontrollable using blood solution,so it is necessary to explore an sustained-release carrier that can control the setting time.OBJECTIVE：To construct an injectable BMP release system by combing rhBMP-2/PLGA microsphere with fibrin glue.DESIGN,TIME AND SETTING：An experimental comparative study was performed at the Department of Othopaedics,General Hospital of Chinese PLA from January 2005 to April 2008.MATERIALS：PLGA （polylactic acid/polyglycolic acid 75/25,Mr=3 000,with 0.025 L/g viscosity） was supplied by Shandong Institute of Medical Instruments;rhBMP-2 was offered by The Academy of Military Medical Sciences;and fibrin glue was supplied by Hangzhou Puji Medicine Technology Development Co.,Ltd.METHODS：The rhBMP-2/PLGA microsphere was prepared using W/O/W solvent evaporation methods.rhBMP-2 loaded PLGA microsphere were incorporated in fibrin glue to establish injectable BMP release system.MAIN OUTCOME MEASURES：The setting time,release behaviors,electron spectroscopy for chemical analysis （ESCA） as well as pH values of composites were measured.RESULTS：①Compared with fibrin glue,the setting time of composites were slightly increased.②Initial burst release of the composites occurred,the drug release exceeded 16.76% within 2 days,and 76.75% of the drug was release within 42 days.③ ESCA showed that composites prolonged release times.④The PH value of composites was between microsphere and fibrin glue.CONCLUSION：RhBMP-2/PLGA microsphere/fibrin glue composite has satisfactory slow-release effect and syringeability,which not only degrade partial acid environment but also maintain the biological effect of higher density.Therefore,it forms a promising synthetic bone graft.
出处
《中国组织工程研究与临床康复》
CAS
CSCD
北大核心
2009年第51期10028-10032,共5页
Journal of Clinical Rehabilitative Tissue Engineering Research
基金
军队“十一五”基金项目资助(06MA259)
北京市自然基金资助(7092098)~~
