# Epigenetic regulation of macrophage response to biomaterial implants

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA-IRVINE · 2020 · $217,917

## Abstract

PROJECT SUMMARY / ABSTRACT
Impaired wound healing is a major clinical problem, and currently available treatment options
often fail to fully repair tissue. Negative pressure wound therapy (NPWT) is a clinically used
treatment that applies a biomaterial scaffold and negative pressure to mechanically stimulate
dermal wounds. However, the mechanisms underlying NPWT remain poorly understood, and
treatment still fails in a significant percentage of patients. Our previous work has established that
topographical properties of biomaterials modulate the function of macrophages, essential innate
immune cells that are involved in both advancing and resolving inflammation, and promoting
tissue repair. More specifically, surfaces that cause macrophage elongation potentiate their
response to wound healing cytokines, and protect cells from inflammation. Interestingly, cell
elongation has been shown to cause profound changes in the epigenetic state of several cell
types including stem cells and adult mesenchymal cells, but the role of epigenetics in biomaterial-
induced macrophage polarization remains completely unknown. In this study, we propose to
investigate the epigenetic regulation of macrophages in response to biomaterials structure during
NPWT. We hypothesize that the structure of the biomaterial scaffold modulates the macrophage
response through changes in the epigenome. We propose to test this hypothesis by: (1)
investigating the effect of biomaterial structure on wound cytokines and cellular infiltrate in
patients undergoing NPWT, and characterize the cellular transcriptomic and epigenomic
landscapes, and (2) examine the effect of biomaterial structure on human macrophage
polarization and epigenome in vitro, and screen the effects of a library of epigenetic modifiers on
the biomaterial-induced macrophage response. The long-term goal of the proposed work is to
better understand regulation of macrophages by the structure of biomaterials, in order to develop
new strategies to promote wound healing and tissue regeneration.

## Key facts

- **NIH application ID:** 9918896
- **Project number:** 5R21EB027840-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Timothy Lamont Downing
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $217,917
- **Award type:** 5
- **Project period:** 2019-04-18 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9918896

## Citation

> US National Institutes of Health, RePORTER application 9918896, Epigenetic regulation of macrophage response to biomaterial implants (5R21EB027840-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9918896. Licensed CC0.

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