# Immunomodulatory biomaterials for regenerative healing of burn wounds

> **NIH VA I01** · VA GREATER LOS ANGELES HEALTHCARE SYSTEM · 2023 · —

## Abstract

During combat, burn injuries to our military personnel often leave our Veterans with severely scarred skin,
painful contractures, with impaired barrier or temperature function. Novel therapies that can prevent or reverse
fibrosis are desperately needed. Outside of fetal wounds, regeneration of native hair follicles, sweat glands, and
adipose tissue, was previously thought impossible. Recent work has shown that, in principle, very large skin
wounds in adult mice can spontaneously regenerate new hair follicles and adipose tissue, while small wounds
or large burn wounds in mice end with the same fate as clinical wounds in humans: fibrotic scarring. We recently
discovered that when our innovative biomaterial, Microporous Annealed Particle (MAP) hydrogel, activates an
immune response, it can induce hair follicle regeneration in small murine wounds that would otherwise heal by
scarring. This proposal combines state-of-the-art molecular, bioinformatic, and bioengineering techniques to: 1)
improve our understanding of why burn wounds in mice result in fibrosis while large excisional wounds result in
regeneration; and 2) use immunomodulatory MAP hydrogel formulations to transform the fibrotic burn wound
microenvironment into one conducive of skin regeneration.
 This application will test our hypothesis that by engineering immunomodulatory MAP hydrogel to specifically
target pro-regenerative immune responses and limit pathways contributing to burn wound fibrosis, we can induce
a highly desirable regenerative response in burn wounds. The first aim will leverage single cell transcriptomics,
a novel bioinformatics methodology to assess cell to cell communication, and loss of function mutants to define
molecular programs responsible for fibrotic wound healing in burn wounds versus regenerative healing in large
excisional wounds at single cell resolution. The second aim will test whether two immunomodulatory MAP
formulations that regenerate hair follicles in small excisional wounds can reprogram immune cell to fibroblast
communication networks in the burn wound microenvironment to activate regeneration. In the third aim, we will
confirm that immune and fibroblast signaling networks in murine fibrosis are active in human burn wounds to
identify novel anti-fibrotic strategies activated in regenerating wounds.
 The proposed studies are significant because they will establish new immune cell-driven mechanism for
diminishing fibrosis and provide opportunities to develop anti-fibrotic and/or proregenerative targets for therapies
for reducing scarring in burn wounds. The proposed studies are innovative because they will establish new
types of immune-modulating biomaterials, and enable a new paradigm of biomaterial-triggered regenerative
response for burn wounds tissues. In the future, the results of this study will drive the development of next-
generation immune-modulating wound biomaterials for potential clinical use.

## Key facts

- **NIH application ID:** 10480614
- **Project number:** 1I01BX005720-01A1
- **Recipient organization:** VA GREATER LOS ANGELES HEALTHCARE SYSTEM
- **Principal Investigator:** PHILIP SCUMPIA
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2023
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2022-11-01 → 2026-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10480614

## Citation

> US National Institutes of Health, RePORTER application 10480614, Immunomodulatory biomaterials for regenerative healing of burn wounds (1I01BX005720-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10480614. Licensed CC0.

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