新型含重组人骨形态发生蛋白2骨修复材料的制备及生物学评价

Preparation and biological evaluation of a novel bone repair material containing recombinant human bone morphogenetic protein-2

背景:含有重组人骨形态发生蛋白2的骨修复材料(骨优导)已经作为国内第1个III类医疗器械注册并获得国家食品药品监督管理局(SFDA)的批准。目的:制备骨修复材料(骨优导),并对其进行生物学评价。设计:分组对比,多角度评估观察实验,于2008-01/07在杭州华东医药集团投资有限公司实验室进行。材料:骨修复材料(骨优导)由杭州华东医药集团投资有限公司提供,是在无菌的洁净车间内,采用基因工程方法,用大肠杆菌发酵技术大规模生产重组人骨形态发生蛋白2,然后与载体材料混合制备得到。方法:根据GB/T16886.12-2005中的规定制备骨修复材料(骨优导)浸提液,按照医疗器械生物学评价方法进行了一系列体内外试验,包括成骨试验、无菌检验、细胞毒性试验、植入试验、热原试验、致敏试验和遗传毒性试验,评价骨修复材料(骨优导)的生物学特性。主要观察指标:各项体内外试验的结果。结果:骨修复材料(骨优导)符合无菌要求,无细胞毒性、无致热原性、无遗传毒性、无致敏性、无组织刺激性,具有良好的组织相容性,且具有异位诱导成骨能力。结论:骨修复材料(骨优导)符合医疗器械骨科植入材料的生物学评价的各项要求。

BACKGROUND： The biological material containing recombinant human bone morphogenetic protein-2（rhBMP-2） has been registered as the first Class Ⅲ medical device and approved by State Food and Drug Administration. OBJECTIVE： To prepare the bone repair material composed with rhBMP-2 and evaluate the biological property of the bone repair material （GuYouDao）. DESIGN, TIME AND SETTING： This study, a grouping comparison and multi-angle evluated observational experiment, was performed at Laboratory of Hangzhou East-China Pharmaceutical Co., Ltd. from January to July 2008. MATERIALS： Bone repair materials （GuYouDao） were supplied by Hangzhou East-China Pharmaceutical Group Investment Co. Ltd. In the aseptic clean workshop, mass production of rhBMP-2 was performed using coli fermentation technology. The bone repair materials were obtained from the rhBMP-2 mixed with their carriers by the gene engineering method. METHODS： Leaching liquor of bone repair material （Guyoudao） was prepared according to GB/T 16886.12-2005 standard. The bone repair material （Guyoudao） was subjected to a series of experiments in vitro and in vivo. The experiments were conducted for the biological characteristics of the bone repair material using biological evaluation methods for medical device, which include tests of bone inductivity, sterility, cytotoxicity, implantation, pyrogen, delayed-type hypersensitivity and genotoxicity. The biological characteristics of the bone repair material were evulated. MAIN OUTCOME MEASURES： The results of these tests in vitro and in vivo. RESULTS： The bone repair material （Guyoudao） was sterile and showed no cytotoxicity, pyrogen, genotoxicity and delayed-type hypersensitivity. It had good biocompatibility in vitro and in vivo. Meanwhile the results also showed that bone rephir material （GuYouDao） could induce ectopic bone formation. CONCLUSION： The bone repair material （Guyoudao） has reached all requests of biological evaluation for medical device.