Effect of human Decellularized Skeletal Muscle on Recovery from Volumetric Muscle Loss Injury

Volumetric muscle loss (VML) overwhelms muscle’s robust capacity for regeneration. A key event in the etiology of VML injury is the bulk loss of structural cues provided by the underlying extracellular matrix (ECM). While muscle is a highly structured tissue, with cell and ECM alignment in the direction of contractile force production, the impact of scaffold alignment on recovery remains unclear. Bulk human decellularized skeletal muscle (DSM) tissues were sectioned into 10 x 1-2 mm fibers. VML defects were repaired using multi-fiber implants consisting of approximately 8 fibers per defect arranged into two layers. Fibers were oriented 1) to the surrounding tibialis anterior (TA) muscle fibers (aligned), or 2) randomly (unaligned) within the defect and coated with minced muscle paste. At 8 weeks, peak tetanic force was not significantly different between the aligned and unaligned repair groups (73%±14% versus 70%±12%). TA muscle mass was also similar between the repair groups. Collagen and Laminin immuno-stains did not reveal structural differences between the groups. The results suggest it may not be necessary to alter the structure of the scaffold to match the surrounding native muscle. This could suggest that cellular and chemical cues provided by the scaffolds are the key design parameters to be considered. Short-term follow-up studies (1 and 2 weeks following repair) may reveal mechanistic insights