Preclinical Assessment of a Compliance Matched Biopolymer Vascular Graft

顺应性匹配的生物聚合物血管移植物的临床前评估

基本信息

批准号：
10366911
负责人：
Jonathan Pieter Vande Geest
金额：
$ 65.86万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-12-15 至 2025-11-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10366911
关键词：
Acute Adult Animal Model Animals Anti-Inflammatory Agents Autologous Bilateral Biopolymers Blood Vessels Bypass Caliber Cells Cessation of life Characteristics Clinical Clinical Treatment Collagen Computer Simulation Coronary Artery Bypass Coronary heart disease Deposition Development Disease Elements Endothelium Environment Exhibits Extracellular Matrix Failure Gelatin Heart Diseases Hyperplasia Implant In Vitro Individual Infiltration Maintenance Mechanics Modeling Myosin Heavy Chains Organ Transplantation Performance Phenotype Play Process Production Rattus Reporting Research Research Project Grants Role Saphenous Vein Sheep Site Smooth Muscle Myocytes Sprague-Dawley Rats Testing Thrombosis Tissue Engineering Tropoelastin United States Vascular Diseases Vascular Graft Vascular Smooth Muscle Woman Work calponin computerized tools controlled release cost efficient design graft failure hemodynamics implantation improved in vivo macrophage mechanical properties men novel pre-clinical pre-clinical assessment preimplantation recruit response thrombogenesis translational potential vascular tissue engineering

项目摘要

Project Summary There are approximately 250,000 coronary artery bypass graft (CABG) procedures performed annually to treat coronary heart disease (CHD) with graft failure rates reported to be as high as 42.8%. A major cause of graft failure in CABG has been attributed to graft compliance mismatch leading to subsequent intimal hyperplasia and graft thrombosis. The development of a compliance matched functional small diameter vascular graft will therefore significantly improve the treatment of those with CHD. Tissue engineering has shown promise in achieving some but not all of the required characteristics for a functional tissue engineered vascular graft (TEVG). A particularly challenging aspect in the development of a functional TEVG is the design of a fully biodegradable biopolymer graft that can be tuned to a desired compliance pre-implantation and subsequently maintain its compliance as it degrades and remodels in-vivo. As such there is a critical need to develop a compliance matched TEVG that remains compliance matched throughout the host remodeling process while also maintaining a functional endothelium. To meet this need we will develop and functionally assess a tropoelastin layered and endothelialized TEVG that is and remains compliance matched. We will utilize computational simulation to optimize the compliance of a biodegradable gelatin/tropoelastin layered TEVG that elutes TGFb2 in a controlled manner to promote early cell infiltration and late matrix deposition in our graft, thus stabilizing its compliance as our graft degrades. The overall working hypothesis of our research is that the intravital (in-vitro and in-vivo) compliance of our graft can be maintained by temporally controlling TGFb2 elution from a computationally optimized TEVG. We will test this hypothesis by completing the following Specific Aims. Aim 1 of our research project will assess if compliance and TGFb2 elution can maintain the compliance of our TEVG in-vivo using a rat aortic interpositional implantation model. Aim 2 of our proposed work will assess the function of our TEVG in a preclinical large animal (sheep carotid) implantation model. The proposed studies will establish a novel pre- and post-implantation compliance controlled fully biodegradable biopolymer TEVG with excellent patency, anti-thrombogenicity, vasoreactivity, and functional performance.

项目摘要每年进行大约250,000个冠状动脉搭桥嫁接（CABG）程序以治疗据报道，冠状动脉疾病（CHD）高达42.8％。移植物的主要原因 CABG的失败归因于移植的合规性不匹配导致随后的内膜增生和移植血栓形成。合规性功能性小直径血管移植的发展将因此，显着改善了冠心病患者的处理。组织工程已经显示出希望实现功能性组织工程血管移植的一些但不是全部所需的特征（tevg）。功能性TEVG开发的一个特别具有挑战性的方面是完全设计可生物降解的生物聚合物移植物，可以调整为所需的合规性植入，然后随后保持其在体内降低和重塑时的合规性。因此，迫切需要开发一个合规性匹配的TEVG在整个主机重塑过程中保持合规性还保持功能性内皮。为了满足这种需求，我们将开发并在功能上评估 Tropoelastin层层和内皮化的TEVG与符合性相匹配。我们将利用计算模拟以优化可生物降解的明胶/tropoelastin层次的合规性。以受控方式消除TGFB2，以促进我们的移植物中的早期细胞浸润和晚期基质沉积，从而稳定其依从性，因为我们的移植物降解。我们研究的总体工作假设是可以通过暂时控制TGFB2来维持我们的移植物的弹力（体外和体体）依从性从计算优化的TEVG中洗脱。我们将通过完成以下内容来检验这一假设具体目标。我们的研究项目的目标1将评估合规性和TGFB2洗脱能否维护使用大鼠主动脉介入植入模型对我们的TEVG体内的合规性。我们提议的目标2 工作将评估我们在临床前大动物（绵羊颈动物）植入模型中的功能。这拟议的研究将建立一种新型的植入前和植入后依从性，完全可完全生物降解生物聚合物TEVG具有出色的通畅性，抗超强性，血管反应性和功能性能。