Microengineering the Dental Pulp Vascular Microenvironment

牙髓血管微环境的微工程

基本信息

批准号：
9981727
负责人：
Luiz Eduardo Bertassoni
金额：
$ 50.31万
依托单位：
OREGON HEALTH & SCIENCE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-08-01 至 2023-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9981727
关键词：
3-Dimensional Address Adult Affect Angiogenic Factor Architecture Biocompatible Materials Biological Blood Vessels Blood capillaries Cell Differentiation process Cells Coculture Techniques Communicable Diseases Cues Dental Materials Dental Pulp Dental caries Dentin Dentistry Development Diffuse Endodontics Endothelial Cells Endothelium Engineering Environment Evaluation Excision Extracellular Matrix Gelatin Goals Heart Human Hydrogels Implant In Vitro Individual Injectable Length Light Mediating Methacrylates Microfluidics Mus Natural regeneration Necrosis Nutrient Odontoblasts Pepsin A Phenotype Plant Roots Polymers Process Property Pulp Canals Role Root Canal Therapy Side Signaling Molecule Site Skin Source Swelling Techniques Testing Tissue Engineering Tissue Model Tissue Survival Tissues Tooth Apex Tooth structure Vascular blood supply Vascularization Waste Products base biomaterial compatibility bioprinting blood vessel development cell motility crosslink dental structure improved in vivo mechanical properties monolayer novel paracrine permanent tooth physical property regenerative response scaffold stem cells success tissue regeneration translational approach vasculogenesis virtual

项目摘要

Project Summary: Dental caries is an infectious disease affecting approximately 90% of adults worldwide. Late stages of caries affect the dental pulp, leading to tissue necrosis and ultimately requiring root canal therapy. Typically, root canals in permanent teeth are treated by removing the necrotic tissue and replacing it with an artificial material. Regenerative endodontics has been proposed as an improved treatment option for these conditions. However, without controllable strategies to engineer the pulp vasculature, effective pulp regeneration is virtually impossible. It has been recently demonstrated that a functional vasculature can be engineered by culturing endothelial cells and stem cells from various sources in the correct microenvironmental conditions. However, the precise requirements specific to regenerating the pulp vasculature remain poorly understood. This project will systematically investigate three overlapping aspects that we propose are key determinants to regenerate the pulp vasculature: (1) matrix physical and mechanical properties, (2) composition, and (3) microarchitecture. In aim 1 we will investigate the contributions of different physical and mechanical properties to the ability of human endothelial colony forming cells (ECFCs) and dental pulp stem cells (DPSCs) to form microvascular networks when embedded in hydrogels that can be photo-crosslinked to have their properties systematically adjusted. We will then engineer pulp tissue-constructs that are pre-vascularized with pre-fabricated endothelial microchannels to enhance pulp regeneration in full-length root canals in-vivo. In aim 2 we will develop injectable and photo-curable hydrogels synthesized from the natural matrix of dentin and modified with methacrylates to test the contribution of matrix composition to the regeneration of the pulp vasculature. Further, we will combine these hydrogels with angiogenic components extracted from the dentin matrix and test their regenerative potential in vitro and in vivo. In aim 3 we will fabricate architecturally controlled gradients of ECFC and DPSC paracrine factors using microfluidics techniques to test the contribution of tissue microarchitecture to the formation of the pulp vasculature. We will then mimic the microarchitectures of vascularized dental pulp by 3D bioprinting tissue constructs that reproduce the organization of the native pulp. In the end of this project we expect to have microengineered a 3D vascularized pulp microenvironment that will improve translational approaches for use in regenerative endodontics in adult teeth.

项目摘要：龋齿是一种传染病，影响了全球约90％的成年人。龋的晚期影响牙髓，导致组织坏死，最终需要根管治疗。通常，根通过去除坏死组织并用人造物质代替永久性牙齿中的运河。已提出再生性牙髓牙齿牙齿牙齿牙齿牙齿药作为改进的治疗选择。然而，如果没有可控策略来设计纸浆脉管系统，有效的纸浆再生实际上是不可能的。最近已经证明，可以通过培养来设计功能性脉管系统在正确的微环境条件下，来自各种来源的内皮细胞和干细胞。然而，再生果肉脉管系统的特定确切要求仍然鲜为人知。这个项目我们建议我们提出的三个重叠方面是重生的关键决定因素果肉脉管系统：（1）基质物理和机械性能，（2）组成和（3）微体系结构。在AIM 1中，我们将研究不同的物理和机械性能对能力的贡献人内皮菌落形成细胞（ECFC）和牙髓干细胞（DPSC）以形成微血管网络嵌入在水凝胶中，可以将照片交联以系统地具有其性能调整。然后，我们将使用预先制作的内皮质体进行果肉组织结构微通道可增强全长根管中的纸浆再生。在AIM 2中，我们将发展可从牙本质的天然基质合成的可注射和光疗水凝胶，并用甲基丙烯酸酯会测试基质组成对果肉脉管系统再生的贡献。此外，我们将将这些水凝胶与从牙本质基质中提取的血管生成成分相结合，测试其在体外和体内的再生潜力。在AIM 3中，我们将制造结构控制的梯度使用微流体技术来测试组织的贡献的ECFC和DPSC旁分泌因子微体系结构，形成纸浆脉管系统。然后，我们将模仿通过3D生物打印组织结构的血管化牙髓，可再现天然纸浆的组织。在该项目的最后改善成人牙齿再生牙髓牙齿牙齿牙齿牙齿牙齿牙齿牙齿牙齿的翻译方法。