Abstract
Dental pulp stem cells (DPSCs) are the primary stem cell source for regenerative endodontics. DPSCs need to undergo a polarization process and retain the permanent polarization status to perform the function of odontoblasts. However, the factors that control DPSC polarization and its underlying mechanism remain unknown. In this study, we established a unique nanofibrous tubular three-dimensional (3D) platform to explore DPSC polarization. The 3D platform has a "clean" background and confines one single DPSC in each microisland of the platform; therefore, it is capable of deciphering any signal that initiates or regulates DPSC polarization. Using the biomimetic platform, we identified that the nanofibrous tubular architecture is the crucial factor to initiate DPSC polarization. Dynamic morphological observation showed that the cellular process of the polarized DPSCs continuously extended and reached a plateau at 72 h. Meanwhile, Golgi apparatus, a cell polarization marker, continuously moved from a juxtanuclear region, passed the nucleus, and eventually settled down at a final position that was a few micrometers away from the nucleus. Inhibition of microfilament and microtubule polymerization demonstrated the indispensable role of cytoskeleton reorganization in modulating DPSC polarization. In addition, cell tension was involved in the regulation of DPSC polarization. The findings of this work expand the in-depth understanding of DPSC polarization, which helps design new bioinspired materials for regenerative endodontics.