Sunday, May 18, 2025
5/18/2025
The pulmonary visceral pleura (PVP) aortic valve - ABSTRACT Aortic stenosis is one of the most common and serious heart valve disease problems, in which the aortic valve opening is narrowed and the left ventricle is under greater load to pump sufficient blood to the body. Transcatheter aortic valve replacement (TAVR) is a minimally invasive and now common approach for treating this disease. However, the long-term durability of transcatheter bioprosthetic valves has become a major concern due to bioprosthetic structural valve degeneration (SVD), a well-known complication post-TVAR and the main cause of impaired valve durability. SVD is a multifactorial process presented as leaflet calcification of the prosthetic valve, leading to valve dysfunction (stenosis and/or wear and tear). To address the SVD and early valve failure, we have identified a new tissue material based on the pulmonary visceral pleura (PVP) that promises to be a superior candidate for the bioprosthetic valve. The bioprosthetic valves for the current TAVR are typically made of bovine or porcine pericardial tissue, which has a collagen-based extracellular matrix (ECM) containing little elastin. In comparison, the PVP contains abundant elastin (ratio of elastin to collagen is ~1:1 in the ECM) and is therefore more resilient, which may lead to less mechanical stresses and improved calcification resistance while providing great hemodynamic performance of the valve. Furthermore, the swine and bovine PVP has a smaller thickness than the pericardium and could thus occupy less volume in the delivery catheter. In our preliminary study, we have demonstrated the xenogeneic PVP’s properties in minimal cytotoxicity, biocompatibility, non-thrombogenicity, mechanical durability, and resistance to calcification through in vivo animal studies. Furthermore, we successfully performed TAVR of the PVP bioprosthetic aortic valve in sheep that showed promising outcomes. In the current proposal, we have assembled a multidisciplinary group of engineers, scientists, and clinicians to launch an integrated study of the PVP aortic valve that includes in vitro experiments, computational modeling, and in vivo animal investigations. The research approach includes accelerated wear tests to study fatigue life and progressive calcification, laser techniques to measure the hemodynamics, high-speed cameras to track leaflet motion, computational modeling of fluid-structure interaction to study hemodynamics, stress distribution, and turbulence characteristics, and in vivo animal study to confirm the performance of the PVP bioprosthetic aortic valve. Our overarching hypothesis is that, due to its high elastin composition, durability, and greater calcification resistance, the PVP valve will outperform the existing bioprosthetic valves in the long term and thus will have a longer lifespan. The success of this proposal would deliver significant benefits to TAVR in managing severe heart valve diseases.
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