Reciprocal effects between scaffold geometry and ventricular vortex flow on viability and performance of tissue-engineered mitral valve

支架几何形状和心室涡流对组织工程二尖瓣的活力和性能的相互影响

• 批准号: 10583424
• 负责人: Arash Kheradvar
• 金额: $ 58.7万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-01-15 至 2027-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10583424
• 关键词: Address; Aorta; Aortic Valve Stenosis; Artificial Heart; Autologous; Biological; Bioprosthesis device; Blood; Blood flow; Cardiac; Cell Survival; Cells; Clinical; Developing Countries; Development; Disease; Endothelial Cells; Engineering; Extracellular Matrix; Generations; Geometry; Heart; Heart Diseases; Heart Valve Diseases; Heart Valves; Homeostasis; Human; Hybrids; Implant; In Vitro; Left; Left atrial structure; Left ventricular structure; Life Expectancy; Link; Long-Term Effects; Mitral Valve; Mitral Valve Stenosis; Morbidity - disease rate; Nature; Patients; Performance; Phenotype; Platelet aggregation; Positioning Attribute; Pre-Clinical Model; Recommendation; Regimen; Reproducibility; Rheumatic Heart Disease; Risk; Shapes; Sheep; Stress; Testing; Thick; Thinness; Thromboembolism; Thrombosis; Tissue Engineering; Tissue constructs; Tissues; United States; Ventricular; attributable mortality; calcification; cardiac tissue engineering; conditioning; design; hemodynamics; implantation; improved; in vivo; insight; interstitial cell; next generation; novel strategies; preclinical study; pressure; prevent; prototype; scaffold; sheep model; tissue regeneration; valvular insufficiency; young adult

PROJECT SUMMURY/ABSTRACT Valvular heart disease (VHD) is the third-most common cause of heart problems in the United States, with mitral valve disease as the second-most common VHD after aortic stenosis. Mitral valve disease can cause many complications if left untreated and is more common in younger patients, in whom bioprosthetic heart valves (BHVs) are prone to faster degeneration. An ultimate solution for younger patients with long life expectancy is a living tissue valve, although exploratory studies for tissue-engineered heart valve (TEHVs) have yet to satisfy the regulatory requirements for clinical use. In preclinical studies, current TEHVs have been unable to adjust their composition to withstand the hemodynamic loads to which they would be exposed, and their leaflets were found to shrink due to their degradable scaffolds, which led to poor leaflet coaptation, followed by progressive regurgitation and valvular insufficiency. The native mitral valve is bileaflet, with a saddle-shaped annulus that bounces dynamically during the cardiac cycle. It forms a diastolic transmitral vortex, which efficiently transfers momentum from the left atrium (LA) toward the aorta via the left ventricle (LV). The transmitral vortex ring is normally non-axisymmetric and helps maximize blood momentum transfer. Inspired by nature's optimizing of the swirling flow in the LV, we aim to gain new insights associated with LV vortex effects on heart valve tissue regeneration toward the development of improved TEHVs, and test those in preclinical studies to be conducted in an ovine model. More specifically, this project seeks to characterize transmitral vortex flow as a link to discovering novel approaches for heart valve tissue engineering to enhance tissue generation and cell viability of the engineered leaflets. We will test the overarching hypothesis that the reciprocal effects between non-axisymmetric vortex flow and mitral TEHVs' scaffold geometry and annulus dynamics enhance tissue generation and improve the valve's cell viability.

项目总结/摘要 瓣膜性心脏病 (VHD) 是美国心脏病的第三大常见原因， 二尖瓣疾病是仅次于主动脉瓣狭窄的第二常见 VHD。二尖瓣疾病可导致 如果不及时治疗，会出现许多并发症，并且在年轻患者中更为常见，其中生物假体心脏 阀门 (BHV) 容易加速退化。为年轻患者提供长寿的终极解决方案 尽管组织工程心脏瓣膜（TEHV）的探索性研究表明预期瓣膜是活体组织瓣膜 尚未满足临床使用的监管要求。在临床前研究中，目前的 TEHV 已 无法调整其成分以承受其将承受的血流动力学负荷，并且 发现它们的小叶由于可降解的支架而收缩，这导致小叶接合不良， 随后出现进行性反流和瓣膜关闭不全。 原生二尖瓣是双叶瓣，具有鞍形环，在心脏跳动期间动态弹跳。 循环。它形成舒张期二尖瓣涡流，有效地传递来自左心房 (LA) 的动量 通过左心室 (LV) 流向主动脉。肱二头肌涡环通常是非轴对称的，有助于 最大化血液动量传递。受自然优化 LV 旋流的启发，我们的目标是 获得与左心室涡流对心脏瓣膜组织再生发展的影响相关的新见解 改进的 TEHV，并在绵羊模型中进行临床前研究中进行测试。更具体地说， 该项目旨在描述二尖瓣涡流的特征，以此作为发现心脏治疗新方法的纽带 瓣膜组织工程，以增强工程小叶的组织生成和细胞活力。我们将测试 总体假设是非轴对称涡流和二尖瓣 TEHV 之间的相互影响 支架几何形状和环面动力学增强了组织生成并提高了瓣膜的细胞活力。