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Regenerative Lipid Mediators for the Management of Severe Burn Wounds

Award Number: R01GM136874
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
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: 02/28/2026

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Regenerative Lipid Mediators for the Management of Severe Burn Wounds - ABSTRACT The treatment of severe burns relies on autologous skin grafts, which are limited due to donor-site unavailability and substantial comorbidities. Current therapies are unable to eliminate substantial healing defects in severe burns, underscoring the urgent needs of more effective therapies. Our long-term goals are to develop better therapies for severe burns. Mesenchymal stem cells (MSCs) possess regenerative power for burn wounds. Adipose-tissue derived microvascular fragments (MVFs) are native vascularization units and a rich source of the MSCs, endothelial cells, perivascular cells, and adipocytes essential in rebuilding burn- destroyed skin. MVFs provide a better niche for MSCs, maximizing MSC regenerative power. MVFs are also easily isolated from fat tissue collected via minimally invasive liposuction. We have identified regenerative lipid mediators (ReLiMs) that increase MSC or MVF proliferation, survival, and production of growth factors, and promote tissue regeneration. ReLiM1 restored impaired vascularization and healing. However, ReLiMs have short half-lives in wounds, limiting their utility for healing burns and functionalizing MSCs. To address this problem, we developed a hydrogel that can sustain ReLiM levels in burn wounds. ReLiM release was sustained from the hydrogel of biodegradable, non-toxic amino acid-based poly(ester amide) protein-mimic polymers (AA-PEAs). The integration of a sustained-release ReLiM with an AA-PEA-hydrogel (Agel) matrix accelerated healing and promoted MSC/MVF functions. We hypothesize that sustained release ReLiMs combined with Agel scaffolds directly promote healing of severe burns and protect and guide MVF regenerative functions. Our objective is to develop ReLiM-impregnated Agels that deliver ReLiMs and provide scaffolds for healing severe burns and protecting and guiding MVF regenerative functions for better healing as well as to decipher the mechanisms via which this occurs. Aim 1. We will develop the Agel to 1A) sustain ReLiM release and to 1B) provide an optimal ReLiM-releasing biomimetic matrix for skin cell homing, vascularization, and re-epithelization, as well as for the reduction of scarring and increasing wound breaking strength. Aim 2. 2A) We will develop a construct that integrates uncultured autologous MVFs, sustained release ReLiMs, and Agel scaffolds to maximize the healing of deep burns. We predict that the achieved construct protects and guides MVF functions. We will verify results using human MVFs in vitro for better translational value. 2B) We will decipher mechanisms for efficacy of the best MVF-ReLiM-Agel. Impact: This project will provide 1) a ReLiM-Agel dressing that delivers ReLiMs and provides a matrix and covering for efficient healing, 2) a ReLiM- and MVF-carrying Agel matrix that protects and guides uncultured MVFs for more efficient healing, and 3) the underlying mechanistic knowledge. These regenerative lipid mediator functionalized dressings with nonexistent or minimal graft-donor requirements are promising adjuvant therapy to overcome the drawbacks of grafting methods or skin substitutes currently used to treat severe burns.


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	LOUISIANA STATE UNIVERSITY HEALTH SCIENCES CENTER NEW ORLEANS	433 BOLIVAR ST RM 619	NEW ORLEANS	LA	70112	ORLEANS	USA	Biomedical Research and Research Training	000	4	6/12/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $455,833 )
2023	2023	LOUISIANA STATE UNIVERSITY HEALTH SCIENCES CENTER-NEW ORLEANS	433 BOLIVAR ST STE 815	NEW ORLEANS	LA	70112	ORLEANS	USA	Biomedical Research and Research Training	000	4	2/13/2023	NON-COMPETING CONTINUATION	$455,833
														Subtotal = $455,833

Issue Date FY: 2022 ( Subtotal = $455,833 )
2022	2022	LOUISIANA STATE UNIVERSITY HEALTH SCIENCES CENTER-NEW ORLEANS	433 BOLIVAR ST STE 815	NEW ORLEANS	LA	70112	ORLEANS	USA	Biomedical Research and Research Training	001	3	6/17/2022	NON-COMPETING CONTINUATION	$45,587
2022	2022	LOUISIANA STATE UNIVERSITY SYSTEM	433 BOLIVAR ST STE 815	NEW ORLEANS	LA	70112	ORLEANS	USA	Biomedical Research and Research Training	000	3	2/18/2022	NON-COMPETING CONTINUATION	$410,246
														Subtotal = $455,833

Issue Date FY: 2021 ( Subtotal = $455,833 )
2021	2021	LOUISIANA STATE UNIVERSITY SYSTEM	433 BOLIVAR ST STE 815	NEW ORLEANS	LA	70112	ORLEANS	USA	Biomedical Research and Research Training	000	2	2/12/2021	NON-COMPETING CONTINUATION	$455,833
														Subtotal = $455,833

Issue Date FY: 2020 ( Subtotal = $721,557 )
2020	2020	LOUISIANA STATE UNIVERSITY SYSTEM	433 BOLIVAR ST STE 815	NEW ORLEANS	LA	70112	ORLEANS	USA	Biomedical Research and Research Training	000	1	4/16/2020	NEW	$471,557
2020	2020	LOUISIANA STATE UNIVERSITY SYSTEM	433 BOLIVAR ST STE 815	NEW ORLEANS	LA	70112	ORLEANS	USA	Biomedical Research and Research Training	001	1	6/12/2020	SUPPLEMENT FOR EXPANSION	$250,000
														Subtotal = $721,557

Grand Total All Awards = $2,089,056

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Regenerative Lipid Mediators for the Management of Severe Burn Wounds

Award Number: R01GM136874

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

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: 02/28/2026

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