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Engineering nitric oxide releasing polymer with immobilized thrombin inhibitor for blood contacting applications

Award Number: R01HL134899
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/01/2017
PERIOD OF PERFORMANCE END DATE: 12/31/2025

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Engineering nitric oxide releasing polymer with immobilized thrombin inhibitor for blood contacting applications - Project Summary/Abstract Currently, clinical applications of intravascular catheters suffer from major challenges: 1) platelet activation and surface-induced thrombosis, 2) biofouling of surfaces with proteins and bacteria, and 3) infection. Thrombus formation can further lead to obstruction of blood vessels, catheter malfunction, or even life-threatening situations such as embolism. Bacterial contamination of catheters causes more than 28,000 deaths per year in the United States, as well as costing the healthcare industry a staggering $2.3 billion. Commercial catheters with heparin- bonded surfaces are available to prevent clotting, but do little to prevent infections. In additions, catheters coated with antiseptics or antibiotics decrease the risk of bacterial infection, but do not prevent biofilm formation that shields bacteria from antibiotics. Therefore, there is a necessity and opportunity to combine strategies for preventing thrombosis and infection into single implantable device coatings for enhanced patency and safety. Our work and others have demonstrated that nitric oxide (NO) release from polymer surfaces can prevent platelet activation and bacterial infection. This technology mimics the vascular endothelial cells lining the blood vessels, as well as other cells in our bodies, producing NO locally to prevent clotting and bacterial biofilm and subsequent infections. Recently we discovered that all of the positive effects can be achieved from polymers impregnated with the NO donor molecule S-nitroso-N-acetylpenicillamine (SNAP), which is nontoxic, inexpensive, and easy to synthesize. Active NO release from the NO donor functionalities in the polymer reduces thrombosis and bacterial infection polymer-blood interface; however, the NO-release strategy alone is limited by the finite reservoir of NO donor functionalities within the polymer that limit the duration of the NO availability at the polymer- blood interface and inability to prevent fibrin formation on the surface. Our recent work has shown the potential of combining active NO-release with catalytic NO-generating mechanism in a single polymer. The goal of this proposal is to develop a polymer comprised of a NO donor impregnated in the polymer to provide active NO-release in combination with immobilized selenocystamine-heparin moieties to provide long-term NO- generation and resist fibrin formation, resulting in a new generation of polymers that possess potent broad-spectrum antimicrobial properties and reduce thrombosis by inhibiting platelet adhesion/activation. The new polymers will be applicable to any blood-contacting device; however, this proposal will focus on studying the combined NO-releasing, catalytic NO generation, and immobilized heparin strategy in long-term (up to 30 d) intravascular catheters on clotting and infection. Successful completion of this project will allow progression to early clinical trials and development of a new generation of catheters that can reduce complications while improving the success of patient care.


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 = $374,185 )
2025	2025	UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.	310 E CAMPUS RD RM 409	ATHENS	GA	30602	CLARKE	USA	Blood Diseases and Resources Research	000	8	12/10/2024	NON-COMPETING CONTINUATION	$374,185
														Subtotal = $374,185

Issue Date FY: 2024 ( Subtotal = $374,185 )
2024	2024	UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.	310 E CAMPUS RD RM 409	ATHENS	GA	30602	CLARKE	USA	Blood Diseases and Resources Research	000	7	12/21/2023	NON-COMPETING CONTINUATION	$336,767
2024	2024	UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.	310 E CAMPUS RD RM 409	ATHENS	GA	30602	CLARKE	USA	Blood Diseases and Resources Research	001	7	7/11/2024	NON-COMPETING CONTINUATION	$37,418
														Subtotal = $374,185

Issue Date FY: 2023 ( Subtotal = $370,870 )
2023	2023	UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.	310 EAST CAMPUS RD TUCKER HALL ROOM 409	ATHENS	GA	30602	CLARKE	USA	Blood Diseases and Resources Research	001	6	3/10/2023	NON-COMPETING CONTINUATION	$37,087
2023	2023	UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.	310 EAST CAMPUS RD TUCKER HALL ROOM 409	ATHENS	GA	30602	CLARKE	USA	Blood Diseases and Resources Research	000	6	12/7/2022	NON-COMPETING CONTINUATION	$333,783
														Subtotal = $370,870

Issue Date FY: 2022 ( Subtotal = $370,870 )
2022	2022	UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.	310 EAST CAMPUS RD TUCKER HALL ROOM 409	ATHENS	GA	30602	CLARKE	USA	Blood Diseases and Resources Research	004	5	9/24/2022	COMPETING CONTINUATION	$0
2022	2022	UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.	310 EAST CAMPUS RD TUCKER HALL ROOM 409	ATHENS	GA	30602	CLARKE	USA	Blood Diseases and Resources Research	003	5	8/17/2022	COMPETING CONTINUATION	$82,254
2022	2022	UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.	310 EAST CAMPUS RD TUCKER HALL ROOM 409	ATHENS	GA	30602	CLARKE	USA	Blood Diseases and Resources Research	001	5	12/31/2021	COMPETING CONTINUATION	$370,870
2022	2020	UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.	310 EAST CAMPUS RD TUCKER HALL ROOM 409	ATHENS	GA	30602	CLARKE	USA	Blood Diseases and Resources Research	002	4	8/17/2022	NON-COMPETING CONTINUATION	-$82,254
2022	2020	UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.	310 EAST CAMPUS RD TUCKER HALL ROOM 409	ATHENS	GA	30602	CLARKE	USA	Blood Diseases and Resources Research	000	4	12/23/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $370,870

Issue Date FY: 2020 ( Subtotal = $382,500 )
2020	2020	UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.	310 EAST CAMPUS RD TUCKER HALL ROOM 409	ATHENS	GA	30602	CLARKE	USA	Blood Diseases and Resources Research	000	4	2/6/2020	NON-COMPETING CONTINUATION	$382,500
														Subtotal = $382,500

Issue Date FY: 2019 ( Subtotal = $382,500 )
2019	2019	UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.	310 EAST CAMPUS RD TUCKER HALL ROOM 409	ATHENS	GA	30602	CLARKE	USA	Blood Diseases and Resources Research	000	3	2/28/2019	NON-COMPETING CONTINUATION	$382,500
														Subtotal = $382,500

Issue Date FY: 2018 ( Subtotal = $392,500 )
2018	2018	UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.	310 EAST CAMPUS RD TUCKER HALL ROOM 409	ATHENS	GA	30602	CLARKE	USA	Blood Diseases and Resources Research	001	2	5/11/2018	NON-COMPETING CONTINUATION	$7,850
2018	2018	UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.	310 EAST CAMPUS RD TUCKER HALL ROOM 409	ATHENS	GA	30602	CLARKE	USA	Blood Diseases and Resources Research	000	2	2/28/2018	NON-COMPETING CONTINUATION	$384,650
														Subtotal = $392,500

Issue Date FY: 2017 ( Subtotal = $375,000 )
2017	2017	UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.	310 EAST CAMPUS RD TUCKER HALL ROOM 409	ATHENS	GA	30602	CLARKE	USA	Cardiovascular Diseases Research	000	1	2/18/2017	NEW	$375,000
														Subtotal = $375,000

Grand Total All Awards = $3,022,610

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Engineering nitric oxide releasing polymer with immobilized thrombin inhibitor for blood contacting applications

Award Number: R01HL134899

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 03/01/2017

PERIOD OF PERFORMANCE END DATE: 12/31/2025

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