# Development of a wound-on-chip model to study stromal-epithelial interactions during tissue repair

> **NIH NIH R21** · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · 2022 · $206,250

## Abstract

The goal of this proposal is to engineer a novel in vitro biomimetic wound healing model to study how human
fibroblasts and epithelial cells coordinate tissue closure at the cellular and molecular level. In vivo wound healing
is a dynamic morphogenetic process with the goal to close and restore the damaged tissue. A critical stage
during tissue closure is re-epithelialization of wounds, a process by which epithelial cells migrate over the
denuded wound bed, to restore the barrier. Failure of wounds to re-epithelialize results in chronic wound
formation, a condition that affect 6 million Americans annually and carries an estimated cost of US $25 billion
per year for the medical system. Hence, understanding the mechanisms that drive re-epithelialization has been
a central focus in wound healing research. Due to limitations with animal models, in vitro models have been
instrumental to study re-epithelialization by human epithelial cells. Traditional models, such as the scratch wound
assay, involve scratching of a monolayer of epithelial cells adherent to a planar substrate, and the time for
migrating cells to repopulate the scratch is measured as a proxy for healing. In more advanced co-culture models,
the planar substrate is either replaced by a fibroblast-laded collagen hydrogel or by a dermal tissue explant.
Whereas these models have a pre-defined substrate as a migration base for epithelial cells, in vivo studies have
shown that for full-thickness wounds, the deeper fibrous layers must heal first through the formation of
granulation tissue by fibroblasts, before epithelial cells can migrate over this provisional tissue to close the
wound. Thus, in in vivo settings, re-epithelialization occurs as fibroblasts deposit a provisional template and
reciprocal interactions between fibroblasts an epithelial cells coordinate closure of these two tissue layers.
Current in vitro models don't capture this intricate tissue dynamics. Given the dependency of re-epithelialization
on the underlying substrate, we hypothesize that fibroblasts mediate the rate of re-epithelialization during wound
closure. To address this hypothesis, we propose in aim 1 to build a biomimetic in vitro wound closure model
wherein re-epithelialization ensues fibrous tissue repair in wounded engineered microtissues to emulate healing
of full thickness wounds. In aim 2, we will use state-of-the art genome editing techniques to elucidate fibroblast-
epithelial interactions that regulate fibrous tissue closure and re-epithelialization. These studies will also validate
and benchmark our 3D biomimetic model to other wound healing models. In aim 3, we will explore whether
fibroblasts from different healthy and pathological tissue sources affect re-epithelialization in our biomimetic
model. Ultimately, this project aims to establish a basis for optimizing a wound bed that enables rapid re-
epithelialization as a paradigm for promoting tissue regeneration and minimizing scarring.

## Key facts

- **NIH application ID:** 10316239
- **Project number:** 5R21EB028491-03
- **Recipient organization:** BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
- **Principal Investigator:** Jeroen Eyckmans
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $206,250
- **Award type:** 5
- **Project period:** 2020-04-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10316239

## Citation

> US National Institutes of Health, RePORTER application 10316239, Development of a wound-on-chip model to study stromal-epithelial interactions during tissue repair (5R21EB028491-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10316239. Licensed CC0.

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