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.
