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

项目摘要/摘要 心脏瓣膜病(VHD)是美国心脏问题的第三大常见原因， 二尖瓣病变为仅次于主动脉瓣狭窄的第二常见的VHD。二尖瓣病变可导致 许多并发症如果不治疗，在较年轻的患者中更常见，在这些患者中，生物假体心脏 阀门(BHV)的退化速度更快。长寿年轻患者的终极解决方案 预期是一个活的组织瓣膜，尽管组织工程心脏瓣膜(TEHs)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 不能调整它们的成分以承受可能暴露在其中的血液动力学负荷，以及 他们的传单被发现由于其可降解的支架而收缩，这导致传单粘合不良， 随后出现进行性反流和瓣膜关闭不全。 固有的二尖瓣是双叶瓣，有一个马鞍形的瓣环，在心脏手术过程中动态反弹。 周而复始。它形成了舒张期的二尖瓣漩涡，有效地传递了左心房(LA)的动量。 通过左心室(LV)朝向大动脉。二尖瓣涡环通常是非轴对称的，有助于 最大限度地转移血液动量。受大自然优化LV内旋流的启发，我们的目标是 获得与心脏瓣膜组织再生的LV涡旋相关的新见解 改进的TEHs，并在将在绵羊模型中进行的临床前研究中进行测试。更确切地说， 该项目试图将二尖瓣涡流表征为发现心脏新方法的纽带。 瓣膜组织工程，以提高工程小叶的组织生成和细胞活性。我们将测试 非轴对称涡流与二尖瓣血流速度相互作用的基本假设 支架的几何形状和瓣环的动力学增强了组织的生成，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.