Development of Bioactive Pulp Capping Material including rhBMP-2

为了开发一种含有重组人骨形态发生蛋白（RhBMP-2）并能诱导钙化的牙髓封盖和截肢材料，我们进行了大量的基础实验，得到了以下结果：动物实验结果表明，玻璃纤维膜可以作为BMP的载体。然而，当使用纤维玻璃膜作为载体时，软骨形成是活跃的，这归因于载体的几何结构。虽然移植后的炎症反应很强，但作为BMP载体，玻璃纤维膜被证明是骨不溶性底物（由于其免疫原性而不适合临床使用）的优越载体。显然，通过改进，可以开发出更好的牙本质形成因子。体外实验试图确定磷脂的功能，磷脂被认为在牙本质钙化中起重要作用。结果表明，结合磷脂的磷酸基起重要作用，但在去磷酸化时，羧基与磷酸基之间的配合作用很重要。也澄清了，不像结合的磷脂，自由的磷脂抑制钙化。对于作为载体的胶原，研究表明胶原纤维的稳定化导致磷脂的共价结合稳定，钙化诱导增强。这些发现阐明了RhBMP-2/磷脂/胶原复合物是硬组织，特别是牙本质的有效诱导剂。也就是说，成功地开发了一种新的纸浆封盖材料。

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.