Wednesday, December 31, 2025 12/31/2025

Nitric oxide-releasing glycosaminoglycans for treating complex wounds

Award Number: R01DK132778
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 01/01/2023
PERIOD OF PERFORMANCE END DATE: 12/31/2026

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Nitric oxide-releasing glycosaminoglycans for treating complex wounds - SUMMARY The delayed healing observed in chronic wounds is exacerbated by persistent microbial infections and non- resolving inflammation. Furthermore, the emergence of antibiotic-resistant bacteria has limited the use of these agents for treating infected wounds. Adding to the complexity of chronic wound treatment, infection is usually not the sole cause of wound chronicity. Underlying diseases such as diabetes leave individuals prone to infection by affecting the host immune responses, including inflammatory cell migration, cell signaling, and effector function. An ideal wound healing therapeutic must thus address the impairment of the host immune response while also possessing antibacterial activity. Due to the high prevalence of chronic wound-related amputations and mortality, the need for such a multi-action therapeutic is urgent. Nitric oxide (NO) is an endogenous signaling molecule that represents an attractive, alternative therapeutic for treating chronic wounds due to its innate antibacterial and immunomodulatory function in human physiology. We have pioneered the development of macromolecular NO donor systems that store and spontaneously release NO in dissolved form (i.e., not as a gas) at therapeutically relevant levels. We now aim to develop NO-releasing glycosaminoglycan biopolymers (GAGs) as wound healing therapeutics. GAGs are naturally occurring biopolymers that are immunomodulatory and known to be involved in wound healing physiology. We hypothesize that combining the multi-faceted roles of GAGs and NO will allow for a therapeutic that effectively: 1) eradicates wound pathogens; 2) modulates inflammation; and, 3) promotes re-epithelialization to facilitate timely wound closure. The objective of this project is to define the roles of GAG molecular weight, sulfation patterns and NO-release properties as they related to antibacterial and pro-wound healing activities. In developing a new class of wound- healing therapeutics, we will characterize cell proliferation, adhesion, and migration as a function of NO payloads and GAG structure using cell culture assays and a three-dimensional human skin tissue model. We will evaluate the effect of NO-releasing GAGs on innate immune cell plasticity using primary human cell systems. We will then determine the therapeutic efficacy of the most promising NO-releasing GAG derivatives on antibacterial action, inflammation, and wound closure as a function of infection and diabetes. An iterative approach will be taken to determine the optimal dose, time, and frequency of therapeutic intervention. A systems biology approach will be used to elucidate mechanisms of efficacy and failure, which will inform clinical translation of these therapeutic approaches. This new research program will allow us to build upon our previous successes in developing NO-releasing macromolecular scaffolds, but now with a focus on wound healing. Our goal is to develop a therapeutic that treats infection and promotes wound healing in populations afflicted by chronic wounds.


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: 2026 ( Subtotal = $381,427 )
2026	2026	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	12/17/2025	NON-COMPETING CONTINUATION	$381,427
														Subtotal = $381,427

Issue Date FY: 2025 ( Subtotal = $343,284 )
2025	2025	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	12/11/2024	NON-COMPETING CONTINUATION	$343,284
														Subtotal = $343,284

Issue Date FY: 2024 ( Subtotal = $366,170 )
2024	2024	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	12/18/2023	NON-COMPETING CONTINUATION	$343,284
2024	2024	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	2	5/8/2024	NON-COMPETING CONTINUATION	$22,886
														Subtotal = $366,170

Issue Date FY: 2023 ( Subtotal = $381,427 )
2023	2023	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	12/16/2022	NEW	$381,427
														Subtotal = $381,427

Grand Total All Awards = $1,472,308

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Nitric oxide-releasing glycosaminoglycans for treating complex wounds

Award Number: R01DK132778

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 01/01/2023

PERIOD OF PERFORMANCE END DATE: 12/31/2026

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