MP29-17 A DECELLULARIZED SKELETAL MUSCLE-DERIVED ECM FOR IN SITU MUSCLE REGENERATION

Abstract

INTRODUCTION AND OBJECTIVE: Cell-based tissue engineering strategies have gained attention in restoring normal tissue function for reconstructive procedures; 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 cell-free muscle-specific scaffolding system that consists of a skeletal muscle-derived decellularized extracellular matrix (dECM) and a myogenic factor, insulin growth factor-1 (IGF-1). We hypothesized that muscle-derived dECM biomaterials combined with IGF-1 could provide a muscle-specific microenvironment for in situ muscle tissue regeneration. We developed a novel dECM-based scaffolding system containing IGF-1 and characterized its rheological properties and in vitro biological properties for tissue reconstruction. METHODS: We developed a novel dECM-based scaffolding system containing IGF-1 and characterized its rheological properties and in vitro biological properties. In addition, we investigated the feasibility of using this dECM-based scaffolding system for in situ muscle tissue regeneration in a rabbit TA muscle defect model. RESULTS: 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 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. CONCLUSIONS: We developed the muscle-specific dECM-based scaffolding system and investigated the synergistic effect of the dECM with IGF-1 for in situ muscle regeneration. The dECM was obtained by the decellularization of skeletal muscle tissue, followed by the solubilization. Combining with IGF-1, the dECM showed high in vitro cellular activities, including cell viability, proliferation, and differentiation. Moreover, in vivo implantation of IGF-1/dECM scaffold in the rabbit TA muscle defect model showed an acceleration in the new muscle formation. We demonstrated that this novel muscle-specific scaffolding system could enhance the body’s regenerative capability for the in situ muscle tissue regeneration, which may have potential utility in reconstruction. Source of Funding: This study was supported by the Musculoskeletal Transplant Foundation (MTF).