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

项目总结/摘要 瓣膜性心脏病（VHD）是美国第三大常见的心脏病原因， 二尖瓣疾病是仅次于主动脉瓣狭窄的第二大常见VHD。二尖瓣疾病会导致 许多并发症，如果不及时治疗，更常见于年轻患者，其中生物假体心脏 瓣膜（BHV）易于更快退化。为年轻患者提供长寿的终极解决方案 预期是活组织瓣膜，尽管组织工程心脏瓣膜（TEHV）的探索性研究 尚未满足临床使用的法规要求。在临床前研究中，目前的TEHV已经 无法调整其成分以承受其可能暴露的血流动力学负荷，以及 发现它们的瓣叶由于其可降解的支架而收缩，这导致不良的瓣叶接合， 随后是进行性反流和瓣膜功能不全。 天然二尖瓣是双叶的，具有在心脏起搏期间动态反弹的鞍形环。 周期它形成一个舒张期的二尖瓣涡流，有效地从左心房（LA）转移动量 经由左心室（LV）朝向主动脉。跨瓣涡环通常是非轴对称的， 最大化血液动量转移。受自然界对LV中旋流的优化的启发，我们的目标是 获得了与左心室涡流对心脏瓣膜组织再生影响相关的新见解， 的改良TEHV，并在绵羊模型中进行的临床前研究中对其进行测试。更具体地说， 该项目旨在描述二尖瓣涡流的特征，作为发现心脏新方法的一个环节。 瓣膜组织工程化以增强工程化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之间的相互作用 支架几何形状和瓣环动力学增强了组织生成并提高了瓣膜的细胞活力。

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.