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殊的形态 执行不同的职能。成牙本质细胞是一种高度极化的牙齿细胞，具有高度的分泌功能 形成牙本质，牙本质是牙齿的主要成分。成牙本质细胞的极化是 牙本质形成具有管状结构的牙本质，对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(DPSCs)可以极化并分化为 成牙本质细胞样细胞。然而，控制DPSC极化的因素和基本机制仍然存在 未知。正因为如此，大多数组织工程方法用于再生性牙髓治疗只能再生 非管状骨样矿化组织。探索DPSC极化的主要障碍是缺乏一种 受启发的三维(3D)“清洁”平台，能够破译生物物理和生化 启动和调节DPSC极化的信号。最近，我们开发了一种受生物启发的管状3D基质 并成功地再生了高度组织化的管状牙本质。此外，我们还鉴定出肾小管 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。在我们的初步研究中，我们进一步开发了一种独特的微图案化和激光消融技术，以 创建一个受生物启发的3D“干净”平台，它可以精确地操作 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化因素。我们假设DPSC偏振是 由一系列生物物理和生化因素启动，这些因素协同作用调节和稳定 偏振的DPSCs。为了实现本项目的总体目标，提出了以下两个目标：目标 第一个是确定启动和调制DPSC极化的生物物理因素；第二个目标是确定 调节DPSC极化的生化因素。成功完成这项工作将从根本上 提高对DPSC极化的认识，极大地促进开发新型生物激励的能力 用于再生牙髓治疗的基质。

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.