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Dual action nanomatrix coated stent evaluation using engineered artery sheets with atherosclerotic features

Award Number: R01HL163802
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Abstract Stents are implanted during the percutaneous treatment of narrowed arteries. However, limitations and unresolved questions remain how to achieve optimal stent patency and safety. Bare metal stent (BMS) deployment remains limited by neointimal hyperplasia caused by vascular injury during stent implantation, leading to in-stent restenosis. To reduce restenosis, a drug-eluting stents (DES), coated with anti-proliferative and/or immuno-suppressive agents targeting neointimal hyperplasia, have been developed. However, recent studies have revealed that the clinically used dose of sirolimus and its analogues for DES cause serious adverse effects including 1) damage to the endothelium that delays re-endothelialization with impaired functions, and 2) inflammation in response to the polymer coating that delivers sirolimus. Another major issue in the stent industry is that outcomes from healthy animal model studies with or without balloon injury do not adequately predict problems found when stents are used in a large number of patients. Thus, there is a critical need to develop an innovative strategy for stent coating and stent evaluation in an atherosclerosis model in order to address 1) adverse effects of clinical dose of sirolimus and 2) “overly optimistic” findings when evaluating stents in a healthy rabbit model. We have successfully developed the nitric oxide (NO) releasing prohealing multifunctional endothelium- mimicking nanomatrix stent coating capable of providing the chemical and biological properties of the native endothelium as demonstrated in vitro, ex vivo, and in a balloon injury healthy rabbit iliac artery model. Notably, we recently found that NO has significant potential to salvage endothelial cell proliferation and migration from the adverse effects of sirolimus while synergistically suppressing smooth muscle cell proliferation. Therefore, we will develop the dual action NO and low-dose liposome-encapsulated sirolimus releasing prohealing nanomatrix in Specific Aim 1. We will also develop novel Engineered Artery Sheets with Atherosclerotic features (eASA) in Specific Aim 2. The efficacy of the dual action NO and sirolimus releasing prohealing nanomatrix compared with commercial BMS and DES will be evaluated under atherosclerotic conditions using the eASA in Specific Aim 2 and in a high fat diet rabbit model in Specific Aim 3. If successful, this novel strategy, combining the unique features of NO and sirolimus will advance the field by overcoming the current limitations of BMS and DES, and with the development of improved in vitro and in vivo models for stent evaluation.


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 = $656,324 )
2024	2024	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH STREET	BIRMINGHAM	AL	35294	JEFFERSON	USA	Cardiovascular Diseases Research	000	3	3/30/2024	NON-COMPETING CONTINUATION	$656,324
														Subtotal = $656,324

Issue Date FY: 2023 ( Subtotal = $595,539 )
2023	2023	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Cardiovascular Diseases Research	000	2	3/24/2023	NON-COMPETING CONTINUATION	$595,539
														Subtotal = $595,539

Issue Date FY: 2022 ( Subtotal = $586,606 )
2022	2022	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Cardiovascular Diseases Research	000	1	3/14/2022	NEW	$586,606
														Subtotal = $586,606

Grand Total All Awards = $1,838,469

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Dual action nanomatrix coated stent evaluation using engineered artery sheets with atherosclerotic features

Award Number: R01HL163802

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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