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

最近的研究表明，骨和骨肉瘤组织中含有一种高度不溶的蛋白质，可以诱导间充质细胞分化为软骨和骨。为了将这种蛋白质BMP应用于临床领域，我们研究了BMP与几种类型的胶原生物材料的骨诱导能力，如下所述。1.胶原蛋白生物材料1)胶原海绵2)胶原蛋白溶液3)胶原膜2.将BMP-胶原复合体移植到小鼠大腿肌肉或骨缺损区，进行X线和组织学观察。结果BMP对各种胶原生物材料均有诱导成骨作用，但BMP-2%胶原溶液无论在肌肉组织还是在骨缺损区均有明显的成骨作用。本研究中使用的BMP是从小牛骨和人罂粟病毒诱发的地鼠骨肉瘤中分离得到的，编号为OS-515。植入后3~4周肌肉组织可见异位骨形成，6~7周可见胶原海绵和胶原膜吸收。结论在骨髓间充质细胞分化为软骨和骨之前，胶原生物材料是保持BMP在同一区域的合适载体。这些胶原蛋白生物材料是可自动消化的，没有明显的组织反应。因此，MBP-胶原生物材料复合体有很好的临床应用前景。

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.