Thursday, November 21, 2024
11/21/2024
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.
HHS’ Tracking Accountability in Government Grants System (TAGGS) website provides access to detailed descriptions of grants, loans, aggregated direct payments and other types of financial assistance awarded by the HHS Operating Divisions (OPDIVs) and the Office of the Secretary Staff Divisions (STAFFDIVs).
