# Defining translational mechanisms to promote regenerative healing of chronic wounds

> **NIH VA I01** · VA CONNECTICUT HEALTHCARE SYSTEM · 2024 · —

## Abstract

Defining translational mechanisms to promote regenerative healing of chronic wounds
Abstract:
Chronic wounds are common among our veterans, often impacting negatively on their ability to
achieve a high quality of life as productive members of our society, and the care of these wounds and
their sequelae consumes a significant portion of resources within the Veterans Health Administration.
The ultimate objective of the research described in this proposal is to develop solutions that allow
durable and regenerative healing of these wounds. Patients who are aged and/or diabetic are at
major risk for developing difficult non-healing wounds, and diabetes occurs among veterans at about
three times the rate of the general US population. To effectively manage these wounds, it is essential
to understand the normal healing process and engineer treatments that promote the physical and
biochemical environment of healing tissue. Pathologically, our identification of specific subclasses of
cells within human skin and how they control skin wound healing carries the potential to ameliorate
skin infections and chronic wounds.
Our long-term goal is to translate our understanding of the cellular and molecular interactions that
drive skin repair into viable treatments for chronic wounds. Our prior work has identified the
importance of cytokines and unique cell types including fibroblast subtypes and macrophages in skin
wound healing in mice. The overall objective of this translational research proposal is to define the
molecular mechanisms by which fibroblast subtypes contribute to wound repair in aged and diabetic
skin and how that can be translated into novel treatment modalities for chronic wounds.
Our central hypothesis is that fibroblast heterogeneity is essential for proper skin repair after injury
and is altered with diabetes and age. This hypothesis is based on our findings that: 1) Multiple
classes of fibroblasts contribute to skin repair after injury; 2) Human skin wounds contain multiple
fibroblast populations; 3) Wound growth factors such as Igf1 specifically contribute to proliferation of
non-fibrotic fibroblast populations in mouse wounds and in vitro and Igf1R expression is altered in
diabetes; 4) Specific populations of fibroblasts are lost in aged skin. Based on these preliminary data,
our record of discovery in skin wound healing, and our team of experts from plastic surgery and skin
cell/developmental biology, we are exceptionally capable of executing the proposed experiments.
We plan to objectively test our central hypothesis and obtain the objective of this proposal by
pursuing the following specific aims: 1) Determine whether the lack of IGF1R in fibroblasts alters
wound healing in mice; 2) Assess the heterogeneity and IGF-1 response of human dermal fibroblast
subpopulations in wounds; and 3) Determine whether transplantation of young fibroblasts and/or
IGF1 treatment can ameliorate wound healing defects in aged and diabetic mouse skin.
We will t...

## Key facts

- **NIH application ID:** 10726558
- **Project number:** 5I01BX005299-03
- **Recipient organization:** VA CONNECTICUT HEALTHCARE SYSTEM
- **Principal Investigator:** Henry C Hsia
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2021-10-01 → 2025-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10726558

## Citation

> US National Institutes of Health, RePORTER application 10726558, Defining translational mechanisms to promote regenerative healing of chronic wounds (5I01BX005299-03). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10726558. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*