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Engineered Anisotropic and Vascularized Human Cardiac Patch

Award Number: R01HL146652
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/26/2021
PERIOD OF PERFORMANCE END DATE: 09/30/2025

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Engineered Anisotropic and Vascularized Human Cardiac Patch - Engineered Anisotropic and Vascularized Human Cardiac Patch Project Summary Currently there are no therapies to effectively reverse cardiac injury following myocardial infarction. Tissue Engineering holds promise for the regeneration of heart tissue through an engineered cardiac patch. Unfortunately, pervious efforts have failed to achieve a cardiac patch with an effective engraftment rate and regenerative efficacy. Human pluripotent stem cell-derived cardiac fibroblasts (hPSCs-CFs) have the potential to provide an unlimited supply of cardiac tissue-specific extracellular matrix (ECM), which could be organized into nanofibers and serve as a universal scaffold to direct the anisotropic orientation of cells and engineered microvessels into a biomimetic hierarchical structure. Human mesenchymal stem cells (hMSCs) are immunomodulatory and effective in promoting myocardial regeneration, and can function as pericytes to mature and stabilize microvessels constructed by endothelial cells. Human pluripotent stem cell-derived cardiomyocytes (hPSCs-CMs) could orchestrate contractile synchrony between the transplanted cardiac tissue and the underlying myocardium. We hypothesize that the combination of hPSCs-CF derived cardiac tissue- specific ECM nanofibers with hMSCs and capillary-like microvessels will significantly enhance the anisotropic cardiac tissue engraftment and effectively promote myocardial regeneration. The objective of the proposed project is to biomimetically engineer an anisotropic cardiac patch containing aligned cardiac tissue-specific nanofibrous ECM, dense and oriented capillary-like microvessels, contractile CMs, and regeneration-promoting hMSCs within a short time. With a strong team comprising of a well-established tissue engineer, a world leading cardiovascular physician-scientist, a very experienced cardiovascular physiologist, an expert in electrophysiology and optical mapping, and an experienced biostatistician, we will pursue the specific aims: I. Derive an aligned and uniform cardiac-specific nanofibrous ECM scaffold from hPSC-CFs. II. Develop an anisotropic, vascularized and contractile cardiac patch representative of native myocardium. III. Evaluate the anastomosis, engraftment and regeneration efficacy of the prevascualrized cardiac patch in a rat MI model.


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 = $0 )
2025	2023	TEXAS A&M ENGINEERING EXPERIMENT STATION	3124 TAMU	COLLEGE STATION	TX	77843	BRAZOS	USA	Cardiovascular Diseases Research	000	4	7/18/2025	NON-COMPETING CONTINUATION	$0
2025	2023	TEXAS A&M ENGINEERING EXPERIMENT STATION	3124 TAMU	COLLEGE STATION	TX	77843	BRAZOS	USA	Cardiovascular Diseases Research	001	4	8/1/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $365,936 )
2023	2023	TEXAS A&M ENGINEERING EXPERIMENT STATION	3124 TAMU	COLLEGE STATION	TX	77843	BRAZOS	USA	Cardiovascular Diseases Research	000	4	7/1/2023	NON-COMPETING CONTINUATION	$365,936
														Subtotal = $365,936

Issue Date FY: 2022 ( Subtotal = $371,481 )
2022	2022	TEXAS A&M ENGINEERING EXPERIMENT STATION	3124 TAMU	COLLEGE STATION	TX	77843	BRAZOS	USA	Cardiovascular Diseases Research	001	3	6/23/2022	NON-COMPETING CONTINUATION	$371,481
2022	2021	TEXAS A&M ENGINEERING EXPERIMENT STATION	7607 EASTMARK DR	COLLEGE STATION	TX	77840	BRAZOS	USA	Cardiovascular Diseases Research	000	2	3/18/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $371,481

Issue Date FY: 2021 ( Subtotal = $344,515 )
2021	2021	TEXAS A&M ENGINEERING EXPERIMENT STATION	7607 EASTMARK DR	COLLEGE STATION	TX	77840	BRAZOS	USA	Cardiovascular Diseases Research	003	2	9/8/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$277,786
2021	2021	TEXAS A&M ENGINEERING EXPERIMENT STATION	7607 EASTMARK DR	COLLEGE STATION	TX	77840	BRAZOS	USA	Cardiovascular Diseases Research	001	2	7/9/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$344,515
2021	2020	MICHIGAN TECHNOLOGICAL UNIVERSITY	1400 TOWNSEND DR	HOUGHTON	MI	49931	HOUGHTON	USA	Cardiovascular Diseases Research	002	1	9/8/2021	NEW	-$277,786
2021	2020	MICHIGAN TECHNOLOGICAL UNIVERSITY	1400 TOWNSEND DR	HOUGHTON	MI	49931	HOUGHTON	USA	Cardiovascular Diseases Research	000	1	7/8/2021	NEW	$0
														Subtotal = $344,515

Issue Date FY: 2020 ( Subtotal = $347,391 )
2020	2020	MICHIGAN TECHNOLOGICAL UNIVERSITY	1400 TOWNSEND DR	HOUGHTON	MI	49931	HOUGHTON	USA	Cardiovascular Diseases Research	000	1	1/8/2020	NEW	$347,391
														Subtotal = $347,391

Grand Total All Awards = $1,429,323

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Engineered Anisotropic and Vascularized Human Cardiac Patch

Award Number: R01HL146652

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 03/26/2021

PERIOD OF PERFORMANCE END DATE: 09/30/2025

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