# Cell-free regenerative approach in wound healing

> **NIH VA I01** · JAMES A. HALEY VA MEDICAL CENTER · 2022 · —

## Abstract

Wounds, which are breaks in structure and function of skin, are healed through a regulated process
initiated with tissue homeostasis followed by repair response involving inflammation, proliferation and
remodeling. Wounds may be due to cuts and lacerations or incisional wounds post surgeries. At times,
this healing is delayed or slowed resulting in chronic recalcitrant wounds. Risk factors for impaired
wound healing include surgical site infection and comorbidities such as aging, smoking, diabetes.
Strikingly, ongoing research with COVID19 patients showcased increased severity in wounds and
lesions compared to normal patients(1-4). Recalcitrant wounds per se are not life-threatening but often
lead to chronic wound related sequelae. The long-term outcome of impaired wound healing may lead
to scarring or amputations, and often has a substantial psychological impact. The treatment of
recalcitrant wounds and stimulation of healing is a critical need and consistent with priorities outlined
by Department of Veterans Affairs (2018-2024 Strategic plan). While multiple advances in wound
dressing materials promote healing, a noteworthy gap remains in the interventions available which
considerably improve the outcome of injury. Towards this goal, a therapeutic approach was
undertaken to harvest the potential of exosomes derived from human adipose stem cells (hASCexo)
mediating tissue repair and regeneration. Thus, the overarching hypothesis is that hASCexo enable
wound healing and recovery of function by modulating genomic pathways following injury. This
project will elucidate the safety and efficacy of hASC exosomes applied topically to repair dermal
wounds to move the therapy closer to the clinic. Towards this goal, the proposal will undertake an in
vitro evaluation of genomic targets complemented with an in vivo approach to determine response to
treatment. These hypotheses will be validated using a multi-disciplinary approach including pre-
clinical, physiological, cellular and biochemical experiments. Specific Aim 1: Determine the molecular
targets of the lncRNA cargo of hASC exosomes that promote wound healing: Using RNAseq to
examine the contents of hASC exosomes, two long noncoding RNAs (lncRNAs) were identified which
are highly enriched in the hASCexo and are pivotal in recovery post injury. Human dermal fibroblasts
(HDF) and human epidermal keratinocytes (HEK) will be used with siRNA mediated knockdown or
over-expression of these lncRNA in hASCexo. Cellular and biochemical outcomes will be measured
in in vitro wound models along with elucidation of genomic changes in response to hASCexo
treatment. These will be validated ex vivo in human skin explants. Specific Aim 2: Evaluation of
response to hASC exosomes’ treatment in an in vivo wound model: The hypothesis is that repair and
regeneration of wounds by topical application of hASCexo depends on its pharmacodynamics and
efficacy. To elucidate this along with its genomic impact, an in vivo rodent isc...

## Key facts

- **NIH application ID:** 10363209
- **Project number:** 1I01BX005591-01A1
- **Recipient organization:** JAMES A. HALEY VA MEDICAL CENTER
- **Principal Investigator:** Niketa A. Patel
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2022
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2022-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10363209

## Citation

> US National Institutes of Health, RePORTER application 10363209, Cell-free regenerative approach in wound healing (1I01BX005591-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10363209. Licensed CC0.

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