Development of a Microstructurally Inspired and Compliance Matched Tissue Enginee

开发受微观结构启发且顺应性匹配的组织工程

基本信息

批准号：
8444206
负责人：
Jonathan Pieter Vande Geest
金额：
$ 19.5万
依托单位：
UNIVERSITY OF ARIZONA
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-01-08 至 2014-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8444206
关键词：
Address Affect Algorithms Animals Applications Grants Architecture Autologous Biochemical Biological Biomechanics Blood Vessels Caliber Cardiovascular Diseases Cardiovascular system Cause of Death Cell Density Cells Cessation of life Collagen Complex Coronary Arteriosclerosis Coronary Artery Bypass Coronary artery Country Coupled Deposition Development Differentiation and Growth Disease Elastin Elements Exhibits Extracellular Matrix Failure Family suidae Fibrin Future Goals Gold Healthcare Heart Diseases Human Hyperplasia Implant Individual Intervention Literature Lysine Mammary Arteries Mechanics Modeling Operative Surgical Procedures Patient Care Patients Performance Polymers Procedures Property Research Research Proposals Saphenous Vein Site Smooth Muscle Myocytes Thick Time Tissue Engineering Tissues Tropoelastin United States Vascular Graft Veins Woman Work biomaterial compatibility cost crosslink implantation in vivo killings meetings men novel public health relevance response

项目摘要

DESCRIPTION (provided by applicant): Heart disease is the leading cause of death for both women and men in the United States. One of the most common forms of heart disease is coronary artery disease (CAD). In 2006 alone, CAD killed 425,245 people, and 176,138 coronary artery bypass grafts were implanted in patients [1]. The need for an alternative vascular substitute is warranted as autologous vessels (e.g., mammary artery, saphenous vein) are oftentimes unavailable due to prior use or cardiovascular disease. Providing a functional tissue engineered vascular graft (TEVG) for CABG surgeries would therefore result in drastic improvements in patient care. Despite significant progress by several research groups in the last few decades, a mechanically and biologically functional TEVG has yet to be developed [22-26]. The overall working hypothesis of this proposal is that a TEVG composed of alternating layers of SMC embedded collagen/fibrin and cross-linked human tropoelastin will result in a vascular substitute that can be compliance-matched to that of a native porcine coronary artery. The primary goal of this research proposal is to fabricate a TEVG that is composed of non-synthetic polymers arranged in a fashion that mimics native vessel architecture and that is compliance matched to a native porcine coronary artery. This goal will be met by completing the following specific aims. Specific Aim 1a: Determine, as a function of time in culture, the biomechanical properties and load dependent extracellular matrix (ECM) microstructural organization of the individual layers to be used in the final optimized TEVG. Specific Aim 1b: Quantify how the addition of exogenous TGF¿2 affects the biomechanical properties and load dependent ECM microstructural organization of the pASMC embedded collagen/fibrin constructs. Specific Aim 2a: Use a computational optimization procedure to identify the optimum number and thickness of alternating tropoelastin and pASMC embedded layers that result in a TEVG whose compliance matches that of porcine coronary artery. Finally, our last aim (Specific Aim 2b) will be to determine if TEVGs fabricated using the optimized parameters (from SA2a) are compliance matched and have similar microstructure to a porcine coronary artery. Successful completion of the proposed aims will result in a TEVG that is constructed entirely from non- synthetic materials, is inspired by native arterial microstructure, and displays the compliance of a functional coronary artery. Our proposed research will also generate novel experimental information on how the compliance and extracellular matrix organization of developing constructs are coupled as they develop in culture. !

描述（由适用提供）：心脏病是美国男女的主要死亡原因。心脏病最常见的形式之一是冠状动脉疾病（CAD）。仅在2006年，CAD就植入了425,245人，患者植入了176,138个冠状动脉搭桥移植物[1]。需要替代血管替代品的需求是因为自体血管（例如乳腺动脉，隐性静脉）通常由于先前使用或心血管疾病而无法获得。因此，提供功能性组织工程的血管移植（TEVG）进行CABG手术，将导致患者护理的大幅改善。尽管在过去的几十年中，几个研究小组取得了重大进展，但机械和生物学功能的TEVG尚未开发[22-26]。该提案的总体工作假设是，由SMC嵌入胶原蛋白/纤维蛋白和交联的人类Tropoelastin的替代层组成的TEVG将导致一种血管替代品，可以合规与天然猪冠状动脉的替代品。该研究建议的主要目的是制造由以模仿本地血管结构的方式排列的非合成聚合物组成的TEVG，并且与本地猪冠状动脉相匹配。该目标特定目标1A：确定，作为培养时间的时间，生物力学性质和载荷依赖性细胞外基质（ECM）微结构组织的各个层的微结构组织，用于最终优化的TEVG。特定目标1B：量化外源TGF¿2的添加如何影响PASMC嵌入的胶原蛋白/纤维蛋白构建体的生物力学特性和依赖载荷的ECM微结构组织。特定目标2A：使用计算优化程序来识别替代性tropoelastin和PASMC嵌入层的最佳数量和厚度，从而导致TEVG的合规性与猪冠状动脉的合规性相匹配。最后，我们的最后一个目标（特定目标2b）将是确定使用优化参数（来自SA2A）制造的TEVG是否合规性匹配，并且与猪冠状动脉具有相似的微观结构。成功完成所提出的目标将导致完全由非合成材料构建的TEVG，灵感来自天然动脉微观结构，并显示功能性冠状动脉的依从性。我们提出的研究还将生成有关如何在文化中发展的发展结构的合规性和细胞外基质组织的新型实验信息。呢