# Proregenerative Immunotherapies for Volumetric Muscle Loss

> **NIH NIH R15** · SAINT LOUIS UNIVERSITY · 2022 · $403,951

## Abstract

ABSTRACT
 Skeletal muscle possesses a remarkable ability to repair and regenerate following moderately severe
injuries (e.g., tears, sprains, etc.). However, following a substantial loss of muscle tissue (>20%), termed as a
volumetric muscle loss (VML), the muscle tissue is unable to repair and regenerate itself. VML injuries show
persistent inflammation and fibrosis at the injury site. Currently, there is no definitive therapy for VML that
regenerates or restores the extensive loss of muscle mass.
 Our previous work revealed a correlation between impaired regeneration and a dysregulated immune
response in VML. This proposal will integrate regenerative and immunomodulatory strategies to boost muscle
recovery post-VML. The proposed regenerative therapy is a biomimetic sponge-like scaffold composed of
extracellular matrix (ECM) proteins. In a rodent model of VML, implantation of this scaffold significantly
enhanced muscle structure and function. This work will modify the scaffold design to achieve sustained release
of an FDA-approved immunosuppressant drug called FK-506 (Aim 1). Sustained release of FK-506 is expected
to modulate the intense and chronic inflammatory response to VML and improve regenerative outcomes.
 Our second approach for VML repair aims to engage and modulate helper T cells. The function of these
cells is primarily mediated through their secreted products. We will identify specific helper T cell subsets that
can promote muscle regeneration. Helper T cell-derived pro-regenerative secretory products will then be locally
delivered to the VML injury site using biomimetic sponges to drive muscle regeneration (Aim 2).
 We will perform a thorough histological, gene & protein expression, and flow cytometry analysis
coupled with peak torque measurement, in both aims to provide mechanistic insight into each therapy. The
proposed plan will provide research training and exposure to both undergraduate and graduate students, making
them more competitive for academic and industry positions.

## Key facts

- **NIH application ID:** 10579498
- **Project number:** 2R15GM129731-02
- **Recipient organization:** SAINT LOUIS UNIVERSITY
- **Principal Investigator:** Koyal Garg
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $403,951
- **Award type:** 2
- **Project period:** 2018-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10579498

## Citation

> US National Institutes of Health, RePORTER application 10579498, Proregenerative Immunotherapies for Volumetric Muscle Loss (2R15GM129731-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10579498. Licensed CC0.

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