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SUMMURY /文摘