# Project 3: Resolution of Surgical Injury

> **NIH NIH P01** · BRIGHAM AND WOMEN'S HOSPITAL · 2020 · $317,013

## Abstract

Project Summary/Abstract
Disruption of the cutaneous barrier by surgery or physical trauma exposes underlying tissue to the environment
and can lead to infection. A robust inflammatory response serves to combat exogenous pathogens in injured
tissue and is tightly coupled to the process of repair. Prolonged or excessive inflammation can impede tissue
repair, suggesting that prompt resolution of inflammation governs this transition. The relationship between
resolution of inflammation and tissue repair is incompletely understood. Resolvins are a family of lipid
mediators generated by immune cells that promote resolution of inflammation and also enhance host defense.
Our recent evidence indicates that resolvins and related pro-resolving mediators also play an important role in
tissue repair. Project 3 of this Program Project will test the hypothesis that D-series resolvins and their newly-
identified sulfido-conjugates (SC) promote cutaneous tissue repair and combat infection following surgical
excisional injury. To test this hypothesis, the following specific aims will be carried out: 1) Assess the role of
resolvins in cutaneous re-epithelialization. We will determine whether resolvins promote re-epithelialization
and determine its relationship to the resolution of inflammation with Projects 1 & 2; 2) Elucidate the temporal
biosynthetic relationships and endogenous roles of D-series resolvins during the inflammatory, proliferative and
remodeling phases of the injury-repair response. Through interactions with Cores B & C and Projects 1 & 2,
we will determine how biosynthesis of D-series resolvins and their SC are regulated during resolution and
tissue repair. We will determine how pro-resolving receptors for RvD1 and RvD2 impact re-epithelialization in
cutaneous surgical injury; 3) Establish the mechanisms whereby resolvins promote re-epithelialization. Using
primary keratinocytes cultured in 2D and 3D, we will determine how resolvins regulate differentiation, migration
and proliferation in a receptor-dependent manner; and 4) Determine whether resolvins restore defective re-
epithelialization by combating bacterial infection. Here, we will examine how infection with skin pathogen,
Staphylococcus aureus, impacts local resolvin biosynthesis and whether resolvins promote bacterial
containment and re-establish epidermal barrier function. Collectively, Project 3 will provide fundamental new
knowledge about the roles of resolvins in tissue repair, which can lead to the development of new therapeutic
approaches for enhancing tissue repair and host defense.

## Key facts

- **NIH application ID:** 9906239
- **Project number:** 5P01GM095467-10
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Matthew R Spite
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $317,013
- **Award type:** 5
- **Project period:** — → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9906239

## Citation

> US National Institutes of Health, RePORTER application 9906239, Project 3: Resolution of Surgical Injury (5P01GM095467-10). Retrieved via AI Analytics 2026-06-10 from https://api.ai-analytics.org/grant/nih/9906239. Licensed CC0.

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