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A preclinical study evaluating and comparing the efficacy of tissue engineered vascular grafts to polytetrafluoroethylene grafts - DIVERSITY SUPP VILLARREAL

Award Number: R01HL163065
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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PROJECT SUMMARY Tissue engineering provides a strategy for developing improved prosthetic biomaterials for use in congenital heart surgery. The overriding premise of our work is that tissue engineering can be used to regenerate autologous neotissue to repair or replace cardiovascular tissues that are congenitally malformed and that the tissue engineered constructs will perform better than prosthetic biomaterials. We developed a tissue engineered vascular graft (TEVG) specifically for use in congenital heart surgery and are currently performing a clinical trial evaluating its safety as an extracardiac conduit in the Fontan operation in which a vascular graft is used to connect the inferior vena cava (IVC) to the pulmonary artery. The broad, long term objective of this study is to translate this technology to the clinic for use in children with congenital heart disease. In order to obtain FDA approval, we must demonstrate the efficacy of the TEVG in a relevant preclinical animal model. The goal of this proposal is to evaluate the late term efficacy of TEVGs compared to PTFE grafts (the current clinical standard of care) using the ovine IVC vascular interposition graft model which we previously developed and validated for this purpose. To this end we propose three specific aims: In the first aim we will evaluate the physiological properties of the TEVG implanted in the ovine model between 9-10 years including compliance and vasoreactivity in addition to growth capacity. We will use intravascular ultrasound (IVUS) and invasive pressure monitoring to measure and compare the compliance of the TEVG and native IVC in age- and sex-matched sheep at various loading conditions. Next we will also use the IVUS and invasive pressure monitoring coupled with pharmacological testing to evaluate and compare the response of the TEVG and the native IVC to various pharmacological reagents at physiologically relevant doses. Finally, we will measure the change in size and geometry of the TEVG using serial 3D angiography to rule out aneurismal dilation and determine the functional growth capacity of the TEVG over the natural life span of the animals in our study. In our second aim we will use computed tomography to evaluate and compare the degree of ectopic calcification between TEVGs and PTFE grafts implanted in the ovine model. In the third aim we will evaluate and compare the hemodynamic performance of TEVGs to PTFE grafts implanted in the ovine model using 4D MRI and invasive hemodynamic monitoring. We will evaluate graft performance both at rest and during simulated stress using dobutamine stress testing then use the 4D flow and invasive hemodynamic pressure data to analyze the degree of disordered flow and associated energy loss within the grafts over cardiac and respiratory cycles at different hemodynamic states using computational fluid dynamics. The development of an improved TEVG with growth capacity has the potential to improve outcomes for children born with congenital heart disease.


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: 2024 ( Subtotal = $51,566 )
2024	2024	RESEARCH INSTITUTE AT NATIONWIDE CHILDREN'S HOSPITAL	700 CHILDRENS DR	COLUMBUS	OH	43205	FRANKLIN	USA	Cardiovascular Diseases Research	000	2	12/7/2023	SUPPLEMENT FOR EXPANSION	$51,566
2024	2024	RESEARCH INSTITUTE AT NATIONWIDE CHILDREN'S HOSPITAL	700 CHILDRENS DR	COLUMBUS	OH	43205	FRANKLIN	USA	Cardiovascular Diseases Research	001	2	12/21/2023	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $51,566

Issue Date FY: 2023 ( Subtotal = $50,861 )
2023	2023	RESEARCH INSTITUTE AT NATIONWIDE CHILDREN'S HOSPITAL	700 CHILDRENS DR	COLUMBUS	OH	43205	FRANKLIN	USA	Cardiovascular Diseases Research	002	2	6/2/2023	NON-COMPETING CONTINUATION	$306,779
2023	2022	RESEARCH INSTITUTE AT NATIONWIDE CHILDREN'S HOSPITAL	700 CHILDRENS DR	COLUMBUS	OH	43205	FRANKLIN	USA	Cardiovascular Diseases Research	001	1	3/1/2023	NEW	$4,296
2023	2022	RESEARCH INSTITUTE AT NATIONWIDE CHILDREN'S HOSPITAL	700 CHILDRENS DR	COLUMBUS	OH	43205	FRANKLIN	USA	Cardiovascular Diseases Research	000	1	2/25/2023	NEW	-$260,214
														Subtotal = $50,861

Issue Date FY: 2022 ( Subtotal = $590,972 )
2022	2022	RESEARCH INSTITUTE AT NATIONWIDE CHILDREN'S HOSPITAL	700 CHILDRENS DR	COLUMBUS	OH	43205	FRANKLIN	USA	Cardiovascular Diseases Research	000	1	6/14/2022	NEW	$590,972
														Subtotal = $590,972

Grand Total All Awards = $693,399

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A preclinical study evaluating and comparing the efficacy of tissue engineered vascular grafts to polytetrafluoroethylene grafts - DIVERSITY SUPP VILLARREAL

Award Number: R01HL163065

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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