Development of Bioactive Pulp Capping Material including rhBMP-2

为了研制一种含有可诱导钙化的重组人骨形态发生蛋白(rhBMP-2)的盖髓和截髓材料，进行了大量的基础实验，取得了以下结果。动物实验结果表明，玻璃纤维薄膜可以作为BMP的载体。然而，当使用玻璃纤维薄膜作为载体时，软骨生成活跃，这归因于载体的几何结构。虽然移植后的炎症反应强烈，但作为BMP的载体，玻璃纤维薄膜是一种优于骨不溶基质的载体(由于其免疫原性，不适合临床使用)。显然，通过改进，可以开发出一种更好的牙本质形成因子。体外实验试图确定被认为在牙本质钙化中发挥重要作用的磷脂的功能。结果表明，磷化产物中的磷酸基起重要作用，但在脱磷时，羧基和磷酸基之间的协同作用是重要的。它还澄清了，与结合磷林不同，游离磷林抑制钙化。对于作为载体的胶原，研究表明，胶原纤维的稳定可以稳定磷脂的共价结合，增强钙化诱导作用，这些结果表明，重组人骨形态发生蛋白-2/磷脂/胶原复合体是一种有效的硬组织诱导剂，尤其是牙本质。也就是说，研制成功了一种新型盖髓材料。

Numerous basic experiments were conducted in order to develop a pulp capping and amputation material containing recombinant human bone morphogenetic protein (RhBMP-2) that can induce calcification, and the following results were obtained.The results of animal experiments have shown that a fibrous glass membrane can act as a BMP carrier. However, when a fibrous glass membrane was used as a carrier, chondrogenesis was active, and this was attributed to the geometric structure of the carrier. While inflammatory reactions following grafting were strong, as a BMP carrier, fibrous glass membrane was shown to be a superior carrier to bone insoluble substrate (not suitable for clinical use due to its immunogenicity). It was clear that, through improvements, a superior dentine formation factor could be developed.In vitro experiments were conducted in an attempt to determine the function of phospholine, which is thought to play an important role in dentine calcification. The results showed that the phosphate-group of bound phospholine played an important role, but when dephosphorylated, the cooperation between the carboxyl group and the phosphate group was important. It was also clarified that, unlike bound phospholine, free phospholine suppresses calcification. With regard to collagen, which is a carrier, it was shown that stabilization of collagen fibers leads to stabilized the covalent binding of phospholine and enhanced calcification induction.These findings clarified that the RhBMP-2/phospholin/collagen complex is an effective inducer of hard tissue, particularly dentine. In other words, a new pulp capping material was successfully developed.