# Tissue mechanics in regenerative wound healing of the skin

> **NIH NIH R01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2021 · $313,500

## Abstract

Summary
 Our long term objective is to heal skin wounds with full functional restoration
(regenerative wound healing) instead of scarring (reparative wound healing). We aspire to learn
what factors control regeneration as supposed to repair during wound healing under the newly
established paradigm of “Wound-Induced Hair Neogenesis” (WIHN). In this model, new hair
follicles emerge from the wound center when a large (>1cm) skin wound is made on the mice
(e.g., C57BL/6). Our new finding in Spiny mice (Acomys) shows, however, that WIHN starts to
form from the periphery of wounds toward the center. Our preliminary data further shows a
distinct spatial distribution of mechanical stiffness across the wound field, and that perturbation
of mechanotransduction in the wound bed alters the outcome of WIHN. These new findings
prompted us to hypothesize that tissue mechanics modulate tissue regeneration and WIHN.
WIHN is easily accessible and is a good model to evaluate this hypothesis. While epithelial
placode formation can be initiated by different chemical morphogens present during embryonic
development (which converge to induce beta-catenin signaling), in WIHN of both C57BL/6 and
spiny mouse, the mechanical environment of the wound can modulate, in parallel or
independently, the threshold of successful placode formation. This acts to alter the status of
epithelia activation, basement membrane remodeling, and dermal condensation. In Aim 1A, we
will compare the different cellular and molecular events leading to WIHN, contrasting spiny and
C57BL/6 mice. Supported by the bioinformatic analyses, Twist1 is proposed as a master
regulator for placode formation in the spiny mouse. Therefore, the role of Twist1 and its
downstream Msx2 in WIHN will be examined in Aim1B. In Aim 2A, we will map the stiffness in
different parts of the wound field employing atomic force microscopy accompanied by cell shape
analyses and FRET-biosensors to indirectly “visualize” the consequence of cell forces within the
wound site. The role of tissue mechanics in WIHN will be further tested by perturbation studies.
Aim 2B will investigate and define the molecular circuits which are functioning in the conductive
mechanical environment for placode regeneration. Overall, the proposal aims to explore novel
epidermal-dermal networks during regenerative wound healing from the perspective of
epigenetic, molecular, and mechanical inputs that construct the grand theme of elements
necessary for future progression of regenerative medicine.
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## Key facts

- **NIH application ID:** 10217187
- **Project number:** 5R01GM125322-04
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Cheng-Ming Chuong
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $313,500
- **Award type:** 5
- **Project period:** 2018-09-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10217187

## Citation

> US National Institutes of Health, RePORTER application 10217187, Tissue mechanics in regenerative wound healing of the skin (5R01GM125322-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10217187. Licensed CC0.

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