# Synthetic Melanin for Accelerating Wound Repair

> **NIH NIH UG3** · NORTHWESTERN UNIVERSITY · 2024 · $536,233

## Abstract

PROJECT SUMMARY
Mustard gas causes severe epithelial and deep tissue injury resulting in blisters, pain, delayed wound healing, and
scarring. The complex mechanism of tissue damage following nitrogen mustard (NM) and sulfur mustard (SM)
exposure involves an initial phase of rapid damage. This phase is characterized by acute damage to epidermal
keratinocytes and to the basement membrane attaching the top layers of the skin with the underlying dermis. This
initiates a cascade of reactions including the release of inflammatory cytokines that signal for the migration of
immune cells into the skin from the circulation. The activity of tissue-infiltrating immune cells constitutes a
secondary ‘hit’ to the initial, chemical-induced burn. This culminates in prolonged skin inflammation leading to
protracted healing and scarring. In a clinical trial, we acquired skin tissue from human subjects experimentally
exposed to NM. From those studies we collected ‘omics’ data, which we have utilized to guide experimental models
and translationally relevant milestones in the development of therapeutic strategies. In preliminary studies, we
hypothesized that the skin’s response to NM would be blunted via the topical application of a persistent, stable
radical scavenger in the form of a synthetic mimetic of human eumelanin. That is, by mimicking the natural function
of melanin as a skin protective antioxidant, we would set the wound site on a path towards reparative healing.
Indeed, in studies in mice and in human skin explants, we observed that topically applied synthetic melanin particles
(SMPs) significantly increase the rate of repair. Therefore, in the UG3 phase, we will leverage our experience with
mustard and our abundant access to fresh human skin tissue, to evaluate a select group of SMPs for their ability
to mitigate the initial injury and to accelerate wound healing. The first selection criterion will be the ability of a given
SMP to prevent sub-epidermal separation (blistering) in human skin explants. The second criterion is mitigation of
keratinocyte necrosis. The third is a demonstration of inhibition of key biomarkers of epidermal damage. These
criteria, tested in human skin explants, will lead to the advancement of six candidates for in vivo evaluation in our
established NM mouse model. Here, the first criterion is a demonstration of reduced wound area size (early-stage)
and rapid re-epithelialization (late-stage). Next, a successful SMP will lead to reduced scar formation and inhibition
of hallmark skin damaging factors. This algorithm will lead to endpoint-driven prioritization and selection of two
SMPs; a lead and back-up candidate to bring forward to the next phase. In the UH3 phase, we will evaluate the
two SMPs in a NM porcine model. This model is adapted from FDA-enabling studies that includes a demonstration
of in vivo 21-day wound reduction coupled with assessment using a 15-point histology grading instrument. Studies
in this phase will involve...

## Key facts

- **NIH application ID:** 10954179
- **Project number:** 1UG3AR084667-01
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Nathan Claude Gianneschi
- **Activity code:** UG3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $536,233
- **Award type:** 1
- **Project period:** 2024-09-04 → 2029-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10954179

## Citation

> US National Institutes of Health, RePORTER application 10954179, Synthetic Melanin for Accelerating Wound Repair (1UG3AR084667-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10954179. Licensed CC0.

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