A Microfabrication Platform for Direct Printing Vascularized Functional Tissue Co

描述（由申请人提供）：我们研究的长期目标是设计复杂的生物材料支架，可以模拟心脏组织的微观结构，并增加再生治疗。这些类组织结构将具有天然组织的适当微结构特征，包括功能正常的脉管系统。为了制造这些组织，我们感兴趣的是使用天然分子，如透明质酸（HA，也称为透明质酸）为基础的生物材料，因为透明质酸在组织的细胞外基质（ECM）中无处不在，而且透明质酸在伤口愈合中固有地起着重要作用。拟议研究的目的是开发方法来创建具有复杂内部结构和细胞封装的天然ECM组件的3D支架。为了制造这样的支架，我们将开发一种基于投影式立体光刻（SL）方法的创新直写平台，称为PSL。在具体目标1中，我们将开发和优化PSL系统，用于使用HA与arg - gy - asp （RGD）和基质金属蛋白酶（MMP）制造3D微结构。在特异性目标2中，我们将使用PSL用于包封心肌细胞的直写3D血凝素支架。在特定的目标3，我们将创建血管化的结构在3D支架和分析血管功能。我们将在微通道内植入内皮细胞。通过调整细胞播种密度、播种时间和表面化学来优化播种过程。这些工程组织结构的血管功能和生物力学特性将在体外确定。

DESCRIPTION (provided by applicant): The long term goal of our research is to design complex biomaterial scaffolds that can mimic the micro- architecture of cardiac tissues and to augment regeneration therapies. These tissue-like structures will have the appropriate microarchitectural features of native tissues including a functioning vasculature. To fabricate these tissues we are interested in using natural molecules such as hyaluronic acid (HA; also called hyaluronan)-based biomaterials, because of the ubiquitous presence of HA in the extracellular matrix (ECM) of tissues and the significant role that HA inherently plays in wound healing. The objective of the proposed research is to develop methods to create 3D scaffolds of native ECM components with complex internal architecture and cell encapsulation. To fabricate such scaffolds, we will develop an innovative direct-write platform based on a projection-style stereolithographic (SL) method, coined as PSL. In Specific Aim 1, we will develop and optimize the PSL system for the fabrication of 3D microstructures using HA with Arg-Gly-Asp (RGD) and matrix metalloproteinase (MMP). In Specific Aim 2, we will use PSL for Direct-write 3D HA scaffolds encapsulating cardiomyocytes. In Specific Aim 3, we will create vascularized structures in a 3D scaffold and analyze vasculature functions. We will seed an endothelial cell lining within microchannels. The seeding process will be optimized by adjusting the cell seeding density and duration as well as surface chemistry. The vascular function and biomechanical properties of these engineered tissue constructs will be determined in vitro. PUBLIC HEALTH RELEVANCE: This project seeks to develop a novel biofabrication platform to create three-dimensional (3D) scaffolds of native extracellular matrix components with complex internal architectures and cell encapsulation. The goal of the project is to create vascularized structures in the 3D scaffolds