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

Award Number: R01HL162687
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 01/15/2023
PERIOD OF PERFORMANCE END DATE: 12/31/2027

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


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $561,129 )
2025	2025	UNIVERSITY OF CALIFORNIA IRVINE	160 ALDRICH HALL	IRVINE	CA	92697	ORANGE	USA	Cardiovascular Diseases Research	000	3	12/20/2024	NON-COMPETING CONTINUATION	$505,017
2025	2025	UNIVERSITY OF CALIFORNIA IRVINE	160 ALDRICH HALL	IRVINE	CA	92697	ORANGE	USA	Cardiovascular Diseases Research	001	3	7/31/2025	NON-COMPETING CONTINUATION	$56,112
														Subtotal = $561,129

Issue Date FY: 2024 ( Subtotal = $631,694 )
2024	2024	UNIVERSITY OF CALIFORNIA IRVINE	160 ALDRICH HALL	IRVINE	CA	92697	ORANGE	USA	Cardiovascular Diseases Research	001	2	6/14/2024	NON-COMPETING CONTINUATION	$51,568
2024	2024	UNIVERSITY OF CALIFORNIA IRVINE	160 ALDRICH HALL	IRVINE	CA	92697	ORANGE	USA	Cardiovascular Diseases Research	000	2	12/15/2023	NON-COMPETING CONTINUATION	$580,126
														Subtotal = $631,694

Issue Date FY: 2023 ( Subtotal = $586,979 )
2023	2023	UNIVERSITY OF CALIFORNIA, IRVINE	160 ALDRICH HALL	IRVINE	CA	92697	ORANGE	USA	Cardiovascular Diseases Research	000	1	1/13/2023	NEW	$586,979
														Subtotal = $586,979

Grand Total All Awards = $1,779,802

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

Award Number: R01HL162687

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 01/15/2023

PERIOD OF PERFORMANCE END DATE: 12/31/2027

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