Resolution of the wound healing mechanism of dertin-pulp complex and application of the knowledge on it to regenerative medicine

本课题针对牙本质再生治疗及其技术的发展，进行了各种实验，得到以下结果：在体外实验中发现海藻酸凝胶作为牙本质再生支架的作用，神经营养因子影响牙髓细胞的分化和矿化，tenascin抑制牙髓细胞内的细胞粘附，并通过生长因子调节tenascin表达的变化调节细胞粘附，BMP-2加入牙髓细胞后，DSPP mRNA表达增强，基质数量增加。以及PDGF在牙髓组织伤口愈合过程中参与牙本质形成等。另一方面，体内实验表明，磷酸horynl -胶原复合物是BMP-2的有效载体，CCl2激光与粘接复合树脂联合应用直接盖髓是有效的，髓组织中含有具有硬组织形成活性的物质和细胞，磷酸钙水泥具有良好的生物相容性，可作为盖髓材料。rFIP-2B mRNA在牙髓细胞创面愈合过程中表达增加，该基因启动子被创面刺激激活，牙髓干细胞导入方法在牙本质再生中是有效的，EMD在牙髓组织创面部分环境最佳时促进牙本质再生，金属硫蛋白在牙髓组织创面制备后参与牙髓细胞的增殖和分化。细胞死亡控制在牙本质创面愈合过程中具有重要意义等。本课题研究结束后，将继续开展指导牙本质有效再生技术的进一步实验。

In this subject, aiming at development of dentin regeneration therapy and its technology, various experiments were conducted, and the following results were obtained.In vitro experiments, it became clear that alginic acid gel is useful as scaffold for dentin regeneration, that neurotrophic factor affects differentiation and mineralization of a pulp cells, that tenascin inhibits cell adhesion in pulp cells and cell adhesion is adjusted through the change of tenascin expression regulated by the growth factor, that expression of DSPP mRNA becomes strong and the amount of matrix increases when BMP-2 is added onto the pulp cells, and that PDGF participates in dentin formation in the wound healing process of pulp tissue, etc. On the other hand, in vivo experiments, it became clear that phosphophorynlcollagen complex serves as effective carrier of BMP-2, that the combined use of CCl2 laser and adhesive composite resin in direct pulp capping is effective, that pulp tissue contains the substance and cell which have hard tissue formation activity, that calcium phosphate cement are excellent in biocompatibility and it can be applied as pulp capping material, that rFIP-2B mRNA expression increases in the wound healing process in pulp cells and the promoter of this gene is activated by wound stimulus, that pulp stem cell introducing method is effective in dentin regeneration, that EMD promotes dentin regeneration when the environment of wound part of pulp tissue is optimum, that metallothionein participates in proliferation and differentiation of pulp cells in wound healing of pulp tissue after cavity preparation, and that cell death control is very important in wound healing process of pulp tissue, etc.Further experiments for developing technology which guides effective regeneration of dentin is to be continued after this research subject is over.