Effect of chemical immobilization of SDF-1α into muscle-derived scaffolds on angiogenesis and muscle progenitor recruitment

The availability of three-dimensional bioactive scaffolds with enhanced angiogenic capacity that have the capability to recruit tissue specific resident progenitors is of great importance for the regeneration of impaired skeletal muscle. Here, we have investigated whether introduction of chemoattractant factors to tissue specific extracellular matrix promotes cellular behaviour in vitro as well as muscle progenitor recruitment and vascularization in vivo. We developed an interconnective macroporous sponge from decellularized skeletal muscle with maintained biochemical traits of the intact muscle. SDF-1α, a potent cell homing factor involved in muscle repair, was physically adsorbed or chemically immobilized in these muscle-derived sponges. The immobilized sponges showed significantly higher SDF-1α conjugation efficiency along with improved metabolism and infiltration of muscle-derived stem cells in vitro, and thus generated uniform cellular constructs. In vivo, femoral muscle implantation in rats revealed a negligible immune response in all scaffold groups. We observed enhanced engraftment, neovascularization, and infiltration of CXCR4⁺ cells in the immobilized-SDF-1α sponge compared with nonimmobilized controls. Although Pax7⁺ cells identified adjacent to the immobilized-SDF-1α implantation site, other factors appear to be necessary for efficient penetration of Pax7⁺ cells into the sponge. These findings suggest that immobilization of cell homing factors via chemical mediators can result in recruitment of cells to the microenvironment with subsequent improvement in angiogenesis.