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：
8603278
负责人：
Jonathan Pieter Vande Geest
金额：
$ 17.01万
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 2015-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8603278
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（由申请人提供）：心脏病是美国女性和男性死亡的主要原因之一，其中最常见的心脏病是冠状动脉疾病 (CAD)，仅 2006 年就导致 425,245 人死亡。，并有 176,138 例冠状动脉旁路移植物被植入患者体内 [1]，需要替代的血管替代物作为自体血管（例如，乳腺血管）。因此，尽管几个研究小组在过去几年中取得了重大进展，但由于先前使用过或患有心血管疾病，为 CABG 手术提供功能性组织工程血管移植物 (TEVG) 仍会导致患者护理的巨大改善。几十年来，机械和生物功能的 TEVG 尚未开发出来 [22-26] 该提案的总体工作假设是 TEVG 由嵌入胶原/纤维蛋白和 SMC 的交替层组成。交联的人弹性蛋白原将产生一种血管替代品，其顺应性与天然猪冠状动脉的血管替代品相匹配。本研究提案的主要目标是制造由以某种方式排列的非合成聚合物组成的 TEVG。模仿天然血管结构并且与天然猪冠状动脉相匹配这一目标将通过完成以下具体目标 1a 来实现：确定作为培养时间的函数。最终优化的 TEVG 中使用的各个层的生物力学特性和负载依赖性细胞外基质 (ECM) 微观结构组织：量化如何添加外源 TGF¿ 2 影响 pASMC 嵌入胶原/纤维蛋白构建体的生物力学特性和负载依赖性 ECM 微观结构组织具体目标 2a：使用计算优化程序来确定交替原弹性蛋白和 pASMC 嵌入层的最佳数量和厚度，从而产生具有顺应性的 TEVG。最后，我们的最后一个目标（具体目标 2b）是确定 TEVG 是否使用优化参数制造。 SA2a）与猪冠状动脉的顺应性匹配并且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，其灵感来自于天然动脉微观结构，并显示出功能性的顺应性。我们提出的研究还将产生关于开发结构在培养过程中的顺应性和细胞外基质组织如何耦合的新实验信息！