# The regulatory roles of type III collagen in cutaneous wound healing

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2022 · $400,339

## Abstract

Abnormal wound healing responses, which include both chronic non-healing wounds and excessive
dermal scarring, result in significant morbidity and healthcare expenditures in the United States and
worldwide. The extracellular matrix (ECM) plays a critical role in wound repair through regulation of cell
migration, differentiation, proliferation, and survival, as well as bioavailability of growth factors. Although
type III collagen (Col3), a component of the ECM, is assumed to play an important role in wound repair
due to its increased expression early in this process, its precise role has remained enigmatic. Our studies
indicate that Col3 has a key role in wound healing, distinct from type I collagen (Col1). Specifically,
our in vitro and in vivo published and preliminary data provide evidence that Col3 regulates reparative
cell activities and fate by 1) altering ECM organization and structure to direct mechanical communication
between cells and the matrix; 2) promoting keratinocyte migration to improve reepithelialization; and 3)
limiting scar formation by suppressing the differentiation and persistence of myofibroblasts, the fibrogenic
cells of the wound. Additional preliminary data support that Col3 suppresses myofibroblast differentiation
via 4) binding and sequestering the profibrogenic cytokine transforming growth factor β (TGFβ) through
its N-propeptide, and 5) altering integrin function. The central hypothesis of this proposal is that Col3
directs reparative cell activities and fate to maximize a regenerative response following
cutaneous injury. Our goal is to define the structural and cellular mechanisms of Col3, and to
demonstrate the efficacy of Col3-containing biomaterials to enhance a regenerative response during
wound healing. We propose to accomplish this goal through three major aims: to determine the impact of
Col3 on the collagen fibrous network to modulate collagen fibril characteristics, covalent intermolecular
cross-linking, and viscoelastic properties during scar evolution and to direct keratinocyte migration (Aim
1), to determine the role of Col3 in the differentiation and persistence of fibrogenic myofibroblasts,
specifically its impact on integrin signaling and profibrotic growth factor availability (Aim 2), and to
demonstrate the potential for exogenous Col3 to rejuvenate healing in an impaired murine wound healing
model and to limit scar formation following cutaneous injury in a preclinical porcine model (Aim 3).
Improving our understanding of how Col3 directs a regenerative response during cutaneous wound
repair has the potential to identify new anti-fibrotic therapies for other pathologies such as pulmonary and
renal fibrosis and hepatic cirrhosis; our third aim will also enable us to apply our findings more
immediately to a translatable and safe intervention to treat debilitating chronic wounds and minimize
pathologic scarring. As such, we anticipate it will have a significant impact on human health.

## Key facts

- **NIH application ID:** 10474403
- **Project number:** 5R01GM124091-05
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** SUSAN W VOLK
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $400,339
- **Award type:** 5
- **Project period:** 2018-09-21 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10474403

## Citation

> US National Institutes of Health, RePORTER application 10474403, The regulatory roles of type III collagen in cutaneous wound healing (5R01GM124091-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10474403. Licensed CC0.

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