Bioinstructive scaffolds enhance stem cell engraftment for functional tissue regeneration.

Stem cell therapy is a promising approach for tissue regeneration after traumatic injury, yet current applications are limited by inadequate control over the fate of stem cells after transplantation. Here we introduce a bioconstruct engineered for the staged release of growth factors, tailored to direct different phases of muscle regeneration. The bioconstruct is composed of a decellularized extracellular matrix containing polymeric nanocapsules sequentially releasing basic fibroblast growth factor and insulin-like growth factor 1, which promote the proliferation and differentiation of muscle stem cells, respectively. When applied to a volumetric muscle loss defect in an animal model, the bioconstruct enhances myofibre formation, angiogenesis, innervation and functional restoration. Further, it promotes functional muscle formation with human or aged murine muscle stem cells, highlighting the translational potential of this bioconstruct. Overall, these results highlight the potential of bioconstructs with orchestrated growth factor release for stem cell therapies in traumatic injury.