Mechanisms of functional skeletal muscle repair: critical role of matrix associated IL-33

PROJECT NARRATIVE Skeletal muscle has a remarkable capacity for repair in response to mild trauma, however, the amount of damage associated with volumetric muscle loss (VML) overwhelms the regenerative process, ultimately resulting in scar tissue deposition and compromised functionality. Although treatment options are very limited for VML, the use of bioscaffolds composed of extracellular matrix (ECM) has shown promise in preclinical studies and a 13 patient human cohort study. The proposed studies will define the functions of a newly discovered component of the ECM, interleukin-33 (IL-33), in remodeling after skeletal muscle injury. Apart from the potential use of ECM- associated IL-33 as prognostic biomarker for tissue regenerative capacity, this study will determine if ECM associated IL-33 can be harnessed for tissue engineering/regenerative medicine applications.