The pro-myogenic environment provided by whole organ scale acellular scaffolds from skeletal muscle

With the aim to generate tissue-engineered, implantable devices, we decellularized skeletal muscles from murine hindlimb. To analyze the in vivo biological activity of the acellular scaffold we replaced homologous muscle in syngeneic mice with an acellular scaffold. The implants were analyzed in regard to histocompatibility, bioactivity and degradability at different times from transplantation. The procedure to generate acellular scaffold maintains the molecular components and the three-dimensional architecture of the extracellular matrix (ECM). Scaffolds can be stored for several weeks at +4°C or +37°C in tissue culture conditions; however, the storage at +4°C allows a better preservation of the degradation of ECM components. Transplantation experiments show that the grafts are stable for several weeks in vivo. The transplanted acellular scaffolds are readily colonized by inflammatory cells and myogenic stem cells that lead to de novo formation of muscle fibers. Immunosuppressive treatment enhances myogenesis within the implant. We demonstrate that the acellular scaffold per se represents a pro-myogenic environment supporting de novo formation of muscle fibers, likely derived from host cells with myogenic potential. Our work highlights the fundamental role of this niche in tissue engineering application and unveils the clinical potential of allografts based on decellularized tissue for regenerative medicine.