Clinical Application of Bone Morphogenic Protein (BMP) using Collagen Biomaterials

最近的研究表明，骨和骨肉瘤组织含有一种高度不溶性的蛋白质，可诱导间充质型细胞分化为软骨和骨。为了将这种蛋白BMP应用于临床领域，我们研究了BMP与几种胶原生物材料结合的骨诱导能力，如下所述。1. 胶原蛋白生物材料胶原蛋白海绵胶原蛋白溶液胶原蛋白膜将bmp -胶原复合物移植到小鼠大腿肌或骨缺损区，进行x线和组织学观察。结果观察了不同类型胶原生物材料对BMP的诱导成骨能力，其中BMP-2%胶原溶液混合物在肌肉组织和骨缺损区成骨效果最明显。本研究使用的BMP是从小腿骨和人乳头瘤病毒诱导的仓鼠骨肉瘤中分离出来的，设计为Os-515。植入后3 ~ 4周肌肉组织出现异位骨形成，6 ~ 7周出现胶原海绵和胶原膜吸收。结论胶原生物材料是将BMP保持在同一区域直至间充质细胞分化为软骨和骨的合适载体。这些胶原生物材料是可自消化的，没有明显的组织反应。因此，mbp -胶原复合生物材料具有良好的临床应用前景。

Recent studies have demonstrated that bone and osteosarcoma tissur contains a highly insoluble protein which induces differentiation of mesenchymal-type cells into cartilage and bone. In order to apply this protein, BMP, in the clinical field, we have investigated bone inductive ability of BMP combined with several types of collagen biomaterials as described below. 1. Collagen biomaterials 1) Collagen sponge 2) Collagen solution 3) Collagen membrane 2. Bmp-collagen complex was transplanted into thigh muscle or bone defect region of mouse, and roentgenic and histological observations were performed. Results Although bone inductive ability of BMP with each type of collagen biomaterial was observed, BMP-2%collagen solution mixture was found to show most obvious bone formation either in muscle tissue or bone defect area. BMP used in the present study were isolated from calf bone and human papova virus induced osteosarcoma in hamster designayed as Os-515. Ectopic bone formation in muscle tissues was detected around 3-4 weeks after implantaion, and collagen sponge and collagen membrane were found to absorved around 6-7 week. Conclusion It was found that collagen biomaterials were suitable carriers to keep BMP at the same area until the differentiation of mesenchymal cells into cartilage and bone. These collagen biomaterials were auto-digestable and shown to have no significant tissue reactions. Thus, there may be a good possibility of clinical use of MBP-collagen biomaterial complex.