无定形磷酸钙负载rhBMP-2纳米缓释体的生物相容性及安全性  

Experimental study on the biocompatibility and security of a rhBMP-2 loaded amorphous calcium phosphate delayed release nano-sized material

作　　者：王皓宇[1,2] 吴小涛[1] 张绍东[1] 沈素祥[1] 李延报[3] 杨惠林[4] 唐天驷[4] 

机构地区：[1]东南大学附属中大医院骨科,南京210009 [2]东南大学医学院附属蚌埠第三医院骨科,蚌埠233000 [3]南京工业大学材料学与工程学院,南京210009 [4]苏州大学附属第一医院骨科,苏州215006

出　　处：《中国矫形外科杂志》2008年第22期1720-1723,共4页Orthopedic Journal of China

基　　金：江苏省卫生厅“135工程”重点学科开放课题(K0618)

摘　　要：[目的]观察无定形硫酸钙(ACP)负载重组人骨形态发生蛋白-2(rhBMP-2/ACP)纳米缓释体的生物相容性及安全性,为新型材料的临床应用提供必要的实验依据。[方法]对材料分别进行体外溶血实验、微核实验、急性毒性试验、热原试验、皮内刺激反应实验和短期肌内埋置试验、骨内植入实验。[结果]材料浸提液对兔血无溶血现象,对小鼠骨髓细胞无遗传毒性作用,未引起小鼠急性毒性反应、兔热原反应、兔皮内刺激反应;兔短期肌肉埋置、骨内植入后局部无明显炎症反应、无组织坏死,材料逐渐发生降解,能与组织有机融合。[结论]rhBMP-2/ACP纳米缓释体的生物相容性及安全性符合ISO10993、GB/T16886规定的体内植入物的生物学评价标准,可作为骨修复替代材料用于相关疾病的临床治疗。[ Objective] To study the biocompatibility and security of the recombinant human bone morphogenetic protein-2 （rhBMP-2） loaded amorphous calcium phosphate （ACP） delayed release nano-sized material and investigate the feasibility of the clinical use as a kind of bone substitute in bone engineering. [ Method] The in vitro hemolyzation, cytotoxicity, microkernel test in marrow smear, acute systemic toxicity, pyrogenicity, subcuticular stimulation reaction and short-term intramuscular implantation, as well as endosseous implantation were performed on the rhBMP-2/ACP delayed release nano-sized material. [ Result] The material-extracted liquid induced no hemolyzation, no toxic effects of genetic , no pyrogenic reaction in rabbits, no cytotoxicity cultured in rabbit bone marrow-derived mesenchymal stem cells（BMSCs） in vitro and no acute toxicity in mice. The intramuscular implantation and endosseous implantation in rabbits induced no inflammatory reaction, tissue necrosis and the material was degraded gradually, fused organically with tissues. [ Conclusion ] The biocompatibility and security of the rhBMP-2/ACP delayed release nano-sized material could meet the requirements given in biological standards for implanted biomaterials ISO10993 and GB/T16886, suggesting that it could be a good bone substitution for the clinical trial.

关 键 词：重组人骨形态发生蛋白 无定形硫酸钙 生物相容性 

分 类 号：R318.08[医药卫生—生物医学工程]