Polarization of dental pulp stem cells

项目摘要 细胞极化是许多细胞类型的基本特征，这些细胞类型显示出特定的形态， 执行不同的功能。成牙本质细胞是一种高度分化的牙本质细胞，具有高度的分泌功能 以形成作为牙齿的主要组成部分的牙本质。成牙本质细胞的极化是成牙本质细胞分化的先决条件。 形成具有管状结构的牙本质，这对于维持牙齿的正常生物功能至关重要。 许多研究表明，牙髓干细胞（DPSC）可以极化并分化为 成牙本质细胞样细胞。然而，控制DPSC极化的因素和潜在机制仍然存在 未知因此，目前大多数组织工程学方法只能使牙髓再生 非管状骨样矿化组织。探索DPSC极化的主要障碍是缺乏生物- 灵感三维（3D）“干净”的平台，能够破译生物物理和生物化学 启动和调节DPSC极化的信号。最近，我们开发了一种生物启发的管状3D矩阵， 并成功地再生了高度组织化的管状牙本质。此外，我们发现管状的 合成基质的结构是启动DPSC极化和形成管状的关键生物物理因素 牙本质在我们的试点研究中，我们进一步开发了一种独特的微图案化和激光烧蚀技术， 创建一个生物启发的3D“清洁”平台，可以精确地操纵一个单一的细胞（或多个细胞）， 因此，3D平台的微岛能够破译启动/调节DPSC的信号 极化因此，拟议的项目是使用独特的“干净”3D平台来识别和分析 控制DPSC极化的生物物理和生物化学因素。我们假设DPSC极化是 由一系列生物物理和生物化学因素引发，这些因素协同作用，调节和稳定 极化DPSC。为实现该项目的总体目标，提出了以下两个目标： 目的1是确定启动和调节DPSC极化的生物物理因素;目的2是确定 调节DPSC极化的生化因子。成功完成这项工作将从根本上 推进对DPSC极化的理解，极大地促进开发新的生物启发的能力， 再生牙髓学的基质。

Project Summary Cell polarization is a fundamental feature of many cell types that display specialized morphologies to perform distinct functions. Odontoblasts are a type of highly polarized dental cells with a high secretory function to form dentin that is a major component of a tooth. The polarization of odontoblasts is a prerequisite for the formation of dentin with tubular structure that is crucial for maintaining the normal biological functions of a tooth. Many studies have shown that dental pulp stem cells (DPSCs) can be polarized and differentiated into odontoblast-like cells. However, the factors that control DPSC polarization and the underlying mechanism remain unknown. Because of that, most of tissue engineering approaches for regenerative endodontics only regenerated non-tubular bone-like mineralized tissues. The main obstacle to explore DPSC polarization is the lack of a bio- inspired three-dimensional (3D) “clean” platform that is capable of deciphering the biophysical and biochemical signals that initiate and regulate DPSC polarization. Recently, we developed a bio-inspired tubular 3D matrix and successfully regenerated highly organized tubular dentin. Furthermore, we identified that the tubular architecture of the synthetic matrix is a crucial biophysical factor to initiate DPSC polarization and form tubular dentin. In our pilot study, we have further developed a unique micropatterning and laser ablation technology to create a bio-inspired 3D “clean” platform that can precisely manipulate one single cell (or multiple cells) in a microisland of the 3D platform, therefore, is capable of deciphering the signals that initiate/regulate DPSC polarization. The proposed project, therefore, is to use the unique “clean” 3D platform to identify and analyze the biophysical and biochemical factors that control DPSC polarization. We hypothesize that DPSC polarization is initiated by a set of biophysical and biochemical factors that work synergistically to regulate and stabilize the polarized DPSCs. To accomplish the overall objective for this project, the following two aims are proposed: Aim 1 is to identify biophysical factors that initiate and modulate DPSC polarization; and Aim 2 is to identify biochemical factors that regulate DPSC polarization. Successfully completing this work will fundamentally advance the understanding of DPSC polarization and greatly promote the ability to develop new bio-inspired matrices for regenerative endodontics.