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.

项目摘要/摘要 瓣膜心脏病（VHD）是美国心脏问题的第三大原因， 二尖瓣疾病是主动脉瓣狭窄后的第二常见VHD。二尖瓣疾病可能导致 如果未经治疗，并且在年轻患者中更常见，许多并发症在生物假发中更为常见 阀（BHV）容易更快地变性。寿命长的年轻患者的最终解决方案 预期是一个活组织阀，尽管对组织工程心脏瓣膜（TEHV）的探索性研究 尚未满足临床使用的监管要求。在临床前研究中，当前的TEHV已经 无法调整其成分以承受其将要暴露的血液动力学负荷，并且 由于它们可降解的脚手架，他们的传单被发现缩小，导致传单的coaptation不良， 其次是进行性反流和瓣膜功能不全。 天然二尖瓣是bileaflet，带有鞍形环，在心脏中动态弹跳 循环。它形成了舒张膜涡旋，从左心房（LA）有效地转移动量 通过左心室（LV）朝主动脉迈进。传输涡流环通常非轴对称，有助于 最大化血液动量转移。受大自然对LV中旋转流的优化的启发，我们的目标是 获得与LV涡流对心脏瓣膜组织再生有关开发的新见解 改进的TEHV，并在临床前研究中测试要在卵巢模型中进行的研究。更具体地说， 该项目旨在将特性涡流流动作为发现心脏新颖方法的链接 瓣膜组织工程，以增强工程小叶的组织产生和细胞活力。我们将测试 总体假设是非轴对称涡流流与二尖瓣TEHVS之间的相互影响' 脚手架几何形状和环动力学可增强组织的产生并改善阀门的细胞活力。