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Bioinspired antifouling and thromboresistant polymers for blood-contacting interfaces

Award Number: R01HL151473
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/20/2020
PERIOD OF PERFORMANCE END DATE: 03/31/2024

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Bioinspired antifouling and thromboresistant polymers for blood-contacting interfaces - 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 doped with the NO donor molecule S-nitroso-N-acetylpenicillamine (SNAP), which is nontoxic, inexpensive, and easy to synthesize. Nitric oxide release alone can inhibit platelet function locally at the polymer/blood interface, but it does not prevent fibrinogen adsorption and fibrin formation which plays a key role in a clot formation. Liquid- infused surfaces exhibit resistance to biofouling and protein adsorption. Our recent work has shown that combining slippery tethered liquid-perfluorocarbon (TLP) surfaces with polymers impregnated with NO-releasing moieties reduces protein adsorption and platelet adhesion/activation significantly better than NO-releasing polymers alone. The goal of this proposal is to develop, optimize, and evaluate a novel polymer that will combine agents that inhibit platelet adhesion and activation via impregnated NO-releasing molecules as well as inhibit biofouling using the liquid-infused TLP surfaces. The biomaterials laboratory directed by Dr. Brisbois will develop the synthesis and polymer fabrication methods, optimize the NO release levels, evaluate the durability properties, study the sterilization/storage stability, and evaluate the antimicrobial properties against common microbes associated with catheter infections. Dr. Handa’s laboratory will study the blood-material interactions and also conduct the chronic animal studies to evaluate the catheters for thrombosis and infection. The new polymers will be applicable to any blood-contacting device; however, this proposal will focus on studying the combined antifouling and NO-releasing effects 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: 2023 ( Subtotal = $354,791 )
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	5	3/9/2023	NON-COMPETING CONTINUATION	$354,791
														Subtotal = $354,791

Issue Date FY: 2022 ( Subtotal = $357,599 )
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	4	6/8/2022	NON-COMPETING CONTINUATION	$35,760
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	000	4	3/14/2022	NON-COMPETING CONTINUATION	$321,839
														Subtotal = $357,599

Issue Date FY: 2021 ( Subtotal = $364,265 )
2021	2021	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	3	3/24/2021	NON-COMPETING CONTINUATION	$364,265
2021	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	001	2	12/16/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$372,244
2021	2020	UNIVERSITY OF CENTRAL FLORIDA BOARD OF TRUSTEES, THE	4000 CENTRAL FLORIDA BLVD	ORLANDO	FL	32816	ORANGE	USA	Blood Diseases and Resources Research	000	1	12/11/2020	NEW	-$372,244
														Subtotal = $364,265

Issue Date FY: 2020 ( Subtotal = $372,244 )
2020	2020	UNIVERSITY OF CENTRAL FLORIDA BOARD OF TRUSTEES, THE	4000 CNTRL FLORIDA BLVD	ORLANDO	FL	32816	ORANGE	USA	Blood Diseases and Resources Research	000	1	4/16/2020	NEW	$372,244
														Subtotal = $372,244

Grand Total All Awards = $1,448,899

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Bioinspired antifouling and thromboresistant polymers for blood-contacting interfaces

Award Number: R01HL151473

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/20/2020

PERIOD OF PERFORMANCE END DATE: 03/31/2024

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