Research and development of innovative caries treatment by biotooth transplantation using iPS cells

本研究旨在诱导iPS细胞在具有牙本质小管样孔的三维硅膜支架的机械压缩下向成牙细胞分化。采用优化的方法和材料对膜进行预涂覆，以增强iPS细胞的附着。在压缩强度为19.6 kPa、细胞密度为4.0 × 10 5个细胞/cm2、加载时间为9 h的条件下，有效诱导成牙细胞分化，成牙细胞特异性标记的表达显著增加，细胞突起向膜孔延伸，这是成牙细胞的典型形态学特征。此外，我们还观察到BMP7和Wnt10a的上调以及MAPK信号通路的参与。这些结果提示支架的三维物理结构在成牙细胞分化中的重要性。

The present study aimed at the induction of iPS cells into odontoblastic differentiation in response to mechanical compression of the three-dimensional silicon membrane scaffold with dentinal tubule-like pores. The membrane was precoated with optimal method and materials to enhance iPS cell attachment. The optimal conditions, which were 19.6 kPa in compression magnitude, 4.0x10 5 cells/cm2 in cell density, and 9 hours of loading time, efficiently induced odontoblastic differentiation, showing significantly increased expression of odontoblast specific markers and enhanced elongation of cellular processes into the pore of membrane, a typical morphological feature of odontoblasts. In addition, up-regulation of BMP7 and Wnt10a and the involvement of the MAPK signaling pathway were observed. These results suggested the importance of three-dimensional physical structure of the scaffold in odontoblastic differentiation.