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Principal Investigator: Koyal Garg
Organization: SAINT LOUIS UNIVERSITY
Fiscal Year: 2024
Award: $98,046
Funding agency: National Institute of General Medical Sciences
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, no definitive therapy for VML 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).
This project will benefit from NanoSight Pro instrument for nanoparticle tracking analysis (NTA;
Malvern Panalytical) for the advanced measurement of high-resolution size and concentration of nano- and
bioparticles. Acquiring NTA equipment for my lab can significantly improve lab productivity and experiment
efficiency, reduce scheduling conflicts, enhance data quality, and provide long-term cost savings. This
investment will lead to more productive and reliable research outcomes for my team.
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