Tissue engineering of small diameter vascular graft

小直径血管移植物的组织工程

• 批准号: 7098057
• 负责人: Changyi Chen
• 金额: $ 43.28万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-20 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7098057
• 关键词: angiogenesis; biomaterial compatibility; biomaterial interface interaction; biomechanics; biotechnology; blood coagulation; carotid artery; cell differentiation; cell proliferation; coronary bypass; dogs; enzyme linked immunosorbent assay; fibroblast growth factor; flow cytometry; hemodynamics; host organism interaction; immunocytochemistry; polymerase chain reaction; stem cells; swine; tissue engineering; tissue support frame; vascular smooth muscle; western blottings

DESCRIPTION (provided by applicant): The aim to produce a truly stable artificial blood vessel containing no synthetic material requires invasion and in growth of endothelial cell and smooth muscle cells as well as fibroblasts into the scaffold. This can be achieved either in vivo from the adjacent tissue or circulating cells after implantation, or in vitro by means of cultivated cells. Such graft should not induce substantial inflammatory reactions that could either damage its wall, setting the scene for long term aneurysm formation or trigger acute thrombosis. Based on such tissue engineering principles and our preliminary data, we propose a central hypothesis that a novel small diameter vascular graft can be tissue-engineered from the porcine carotid artery by decellularization, heparin covalent linkage, and heparin binding growth factors, and endothelial progenitor cell (EPC) seeding; and this graft may maintain its mechanical property and natural compliance; reduce host immune response; provide anticoagulation surface; and accelerate vascular cell growth and remodeling, thereby maintaining a long term potency in vivo. Three specific aims are proposed below to test our central hypothesis: Aim 1: To determine the mechanical property, natural compliance, host immune response, and anticoagulation property of decellularized-heparinized porcine carotid artery grafts (D-H grafts). We will test the hypothesis that D-H grafts may maintain their mechanical property and natural compliance, provide anticoagulation surface, and reduce host immune response. Both in vitro and animal models are included. Carotid artery bypass surgery using D-H grafts will be performed in dogs (xenogenic setting) and in pigs (allogenic setting). Aim 2: To determine the effect of bFGF binding to D-H grafts on vascular cell growth and repopulation of the grafts. We will test the hypothesis that bFGF binding to D-H grafts may promote vascular cell growth and repopulation of the grafts, thereby accelerating vascular healing and remodeling. Characteristics of bFGF binding and release and effect on cell proliferation and anticoagulation will be investigated in vitro. In vivo performance of bFGF bound D-H grafts will be studied. Aim 3: To characterize cell proliferation and differentiation of EPC and its application with bFGF bound D-H grafts. We will test the hypothesis that bFGF bound D-H grafts may enhance EPC proliferation and differentiation, and EPC seeded bFGF bound D-H grafts may have better healing and remodeling characteristics as compared to un-seeded grafts. EPC will be isolated and characterized from dog or pig peripheral blood. The effect of bFGF and hemodynamics on EPC differentiation and proliferation will be investigated. In vivo performance of EPC seeded bFGF bound D-H grafts will be studied. This study represents a multidisciplinary approach including tissue engineering, cellular and molecular biology, and animal models. Success of this proposal will directly indicate the clinical applications of tissue engineered small diameter vascular grafts.

描述(申请人提供)：为了制造真正稳定的不含合成材料的人造血管，需要内皮细胞、平滑肌细胞以及成纤维细胞侵入支架，并使其生长。这既可以通过植入后的邻近组织或循环细胞在体内实现，也可以通过体外培养细胞的方式实现。这样的移植物不应该引起实质性的炎症反应，这种反应既可能损害其壁面，为长期动脉瘤的形成奠定基础，也不会引发急性血栓形成。基于这些组织工程学原理和我们的初步数据，我们提出了一个中心假设，即通过去细胞、肝素共价连接和肝素结合生长因子以及内皮祖细胞(EPC)种植，可以从猪颈动脉组织工程化出一种新型的小口径血管移植物，这种移植物可以保持其机械性能和自然顺应性，降低宿主的免疫反应，提供抗凝表面，并促进血管细胞的生长和重塑，从而在体内保持长期的效力。目的1：检测脱细胞肝素化猪颈动脉移植物的力学性能、自然顺应性、宿主免疫反应和抗凝性能。我们将验证D-H移植物可以保持其机械性能和自然顺应性，提供抗凝表面，并降低宿主免疫反应的假设。包括体外模型和动物模型。使用D-H移植物的颈动脉搭桥手术将在狗(异种设置)和猪(同种设置)上进行。目的：研究碱性成纤维细胞生长因子与D-H移植物的结合对移植物血管细胞生长和再分化的影响。我们将验证这一假设，即bFGF与D-H移植物结合可能促进移植物血管细胞的生长和再繁殖，从而加速血管愈合和重塑。我们将在体外研究碱性成纤维细胞生长因子的结合和释放特性，以及对细胞增殖和抗凝的影响。我们将研究碱性成纤维细胞生长因子结合的D-H移植物的体内性能。目的：研究碱性成纤维细胞生长因子结合的D-H移植物对内皮祖细胞增殖和分化的影响。我们将验证这一假说，即碱性成纤维细胞生长因子结合的D-H移植物可以促进内皮祖细胞的增殖和分化，与未种植的移植物相比，EPC种植的bFGF结合的D-H移植物可能具有更好的愈合和重塑特性。内皮祖细胞将从狗或猪的外周血中分离并鉴定。研究碱性成纤维细胞生长因子和血流动力学对内皮祖细胞分化和增殖的影响。EPC种植的碱性成纤维细胞生长因子结合的D-H移植物的体内性能将被研究。这项研究代表了一种多学科的方法，包括组织工程、细胞和分子生物学以及动物模型。该方案的成功将直接预示着组织工程化小口径血管移植物的临床应用。

项目成果

Current advances in research and clinical applications of PLGA-based nanotechnology.

• DOI: 10.1586/erm.09.15
• 发表时间: 2009-05
• 期刊: Expert review of molecular diagnostics
• 影响因子: 5.1
• 作者: Lü JM;Wang X;Marin-Muller C;Wang H;Lin PH;Yao Q;Chen C
• 通讯作者: Chen C

Transforming growth factor-beta increases the expression of vascular smooth muscle cell markers in human multi-lineage progenitor cells.

• DOI: 10.12659/msm.881439
• 发表时间: 2011-02-25
• 期刊: Medical science monitor : international medical journal of experimental and clinical research
• 作者: Yang H;Zhang L;Weakley SM;Lin PH;Yao Q;Chen C
• 通讯作者: Chen C