A novel decellularized skeletal muscle-derived ECM scaffolding system for in situ muscle regeneration

•In situ tissue regeneration is to improve the body’s regenerative ability by mobilizing endogenous stem cells.•A novel muscle-specific scaffold to promote the muscle tissue regeneration in situ.•Tissue-specific microenvironment can be achieved by using decellularized tissues.•Synergistic effect from decellularized extracellular matrices combined with insulin-like growth factor 1. The cell-based tissue engineering strategies have gained attention in restoring normal tissue function after skeletal muscle injuries; however, these approaches require a donor tissue biopsy and extensive cell expansion process prior to implantation. In order to avoid this limitation, we developed a novel cell-free muscle-specific scaffolding system that consisted of a skeletal muscle-derived decellularized extracellular matrix (dECM) and a myogenic factor, insulin growth factor-1 (IGF-1). Rheological, morphological, and biological properties of this muscle-specific scaffold (IGF-1/dECM) as well as collagen and dECM scaffolds were examined. The cell viability in all scaffolds had over 90% at 1, 3, and 7 days in culture. The cell proliferation in the IGF-1/dECM was significantly increased when compared with other groups. More importantly, the IGF-1/dECM strongly supported the myogenic differentiation in the scaffold as confirmed by myosin heavy chain (MHC) immunofluorescence. We also investigated the feasibility in a rabbit tibialis anterior (TA) muscle defect model. The IGF-1/dECM had a significantly greater number of myofibers when compared to both collagen and dECM groups at 1 and 2 months after implantation. We demonstrated that this novel muscle-specific scaffolding system could effectively promote the muscle tissue regeneration in situ.