不同粒径重组人骨形态发生蛋白2/聚乳酸-聚羟基乙酸共聚物微球制备及体内外释放性能比较  

Recombinant human bone morphogenetic protein 2/poly(lactic-co-glycolic acid) copolymer microspheres with different particle sizes: preparation and release performance in vivo and in vitro

作　　者：鲍玉成[1] 王勇[1] 张文龙[1] 谢祎[1] 于美丽[2] Bao Yu-cheng;Wang Yong;Zhang Wen-long;Xie Yi;Yu Mei-li(Tianjin Haihe Hospital,Tianjin 300350,China;Third Central Hospital of Tianjin,Tianjin Key Laboratory of Artificial Cells,Tianjin 300170,China)

机构地区：[1]天津市海河医院,天津市300350 [2]天津市第三中心医院,天津市人工细胞重点实验室,天津市300170

出　　处：《中国组织工程研究》2018年第2期210-215,共6页Chinese Journal of Tissue Engineering Research

基　　金：天津市津南科委科技基金(2015001)

摘　　要：背景:应用生物可降解材料包载骨细胞生长因子制成微球缓释的技术,为生长因子的高效利用提供了可行性。目的:制备重组人骨形态发生蛋白2/聚乳酸-聚羟基乙酸共聚物纳米和微米微球,通过体内外释放实验比较两种微球的释放行为差异。方法:通过控制匀浆速度,采用乳化-溶剂挥发法制备重组人骨形态发生蛋白2/聚乳酸-聚羟基乙酸共聚物缓释纳米和微米微球。(1)体外缓释实验:将两种微球分别溶于PBS中70 d,采用ELISA法检测不同时间点上清液中重组人骨形态发生蛋白2的浓度;(2)体内缓释实验:将44只新西兰大白兔分为2组,分别在股骨转子缺损处植入重组人骨形态发生蛋白2/聚乳酸-聚羟基乙酸共聚物缓释纳米和微米微球,植入70 d内采用ELISA法检测股骨转子缺损处重组人骨形态发生蛋白2的浓度。结果与结论:(1)体外缓释实验:纳米微球前3 d存在突释情况,累计释放将近达到41%,随后呈持续平稳缓慢释放,70 d时达到83%左右;微米微球突释情况较纳米微球小,前3 d累计释放约为20%且持续释放时间长,70 d累计释放约为70%;(2)体内缓释实验:纳米微球前3 d存在突释情况,累计释放将近35%,随后呈持续平稳缓慢释放,70 d时达到72%左右;微米微球突释情况较纳米微球小,前3 d累计释放约为21%且持续释放时间长,70 d累计释放约为63%左右;(3)结果表明:重组人骨形态发生蛋白2/聚乳酸-聚羟基乙酸共聚物微米微球缓释释放时间与骨生长周期相适宜,更有利于临床治疗骨缺损修复。BACKGROUND:The technology of biodegradable materials covering growth factors can be used to make sustained-release microspheres,which provides the feasibility for the efficient utilization of growth factors.OBJECTIVE:To prepare nano/micron-sized spheres using recombinant human bone morphogenetic protein 2/poly(lactic-co-glycolic acid)(rhBMP-2/PLGA)copolymer and to compare their release behaviors by in vivo and in vitro release experiments.METHODS:The rhBMP-2/PLGA nano/micron-sized spheres were prepared by emulsion solvent evaporation method to control the rate of pulp mixing.(1)In vitro release experiment:Prepared nano/micron-sized spheres were dissolved in PBS for 70 days,and then ELISA method was used to detect the rhBMP-2 concentration in the supernatant at different time.(2)In vivo release experiment:Forty-four New Zealand rabbits were divided into two groups,and rhBMP-2/PLGA nano/micron-sized spheres were respectively implanted into trochanteric defects.The concentration of rhBMP-2 in the defect site was detected by ELISA within 70 days after implantation.RESULTS AND CONCLUSION:In vitro sustained release experiment:There was a sudden release of nanospheres in the former 3 days,and the cumulative release nearly reached 41%,followed by a steady and slow release,and then the cumulative release was up to approximately 83%at 70 days.The initial release of micron-sized spheres was less than that of nanospheres,and the cumulative release was about 20%within the former 3 days and reached to 70%at 70 days.In vivo sustained release test:There was a sudden release of the nanospheres,the cumulative release was nearly 35%,followed by a steady and slow release,and then the cumulative release was up to approximately 72%at 70 days.The initial release of micron-sized spheres was less than that of nanospheres,and the cumulative release was about 21%in the former 3 days and increased to about 63%at 70 days.In both in vivo and in vitro release experiments,the release duration of micron-sized spheres was longer than that of nano

关 键 词：骨形态发生蛋白质类 微球体 药物释放系统 组织工程 

分 类 号：R318[医药卫生—生物医学工程]