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，其可以模拟心脏组织的微结构并增强再生治疗。这些组织样结构将具有天然组织的适当微结构特征，包括功能性脉管系统。为了制造这些组织，我们对使用天然分子如透明质酸（HA;也称为透明质酸）基生物材料感兴趣，因为HA在组织的细胞外基质（ECM）中普遍存在，并且HA在伤口愈合中固有地起重要作用。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。为了制造这种支架，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，用于使用具有Arg-Gly-Asp（RGD）和基质金属蛋白酶（MMP）的HA制造3D微结构。在特定目标2中，我们将使用PSL用于包封心肌细胞的直接写入3D HA支架。在具体目标3中，我们将在3D支架中创建血管化结构并分析血管功能。我们将在微通道内植入内皮细胞衬里。将通过调整细胞接种密度和持续时间以及表面化学来优化接种过程。将在体外测定这些工程化组织构建物的血管功能和生物力学性质。 公共卫生相关性：该项目旨在开发一种新型生物纤维素平台，以创建具有复杂内部结构和细胞包封的天然细胞外基质成分的三维（3D）支架。该项目的目标是在3D支架中创建血管化结构

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