biostudies-literatureWu DBLRD VANIA NIH HHSNHLBI NIH HHSRRD VANCI NIH HHSU.S. Department of Health &Human Services | NIH | National Institute on Aging1364-1374https://www.ebi.ac.uk/biostudies/studies/S-EPMC12777987biostudies-literatureUnknown24(9)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.Nature materialsBioinstructive scaffolds enhance stem cell engraftment for functional tissue regeneration.PMC12777987R41 HL170875I01 BX004259R01 CA285372I01 RX001222IK6 BX006309I21 RX004898R21 HL172096P01 AG036695R01 AG068667Kim SYue SHu CFathali IEugenis IRando TAKanugovi AHuang NFWu DWheeler JRShrager JBFeeley SfalseBioinstructive 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.2025-01-01T00:00:00Z2025 Sep2026-06-06T11:50:31.091Z2026-05-30T03:09:00.849ZS-EPMC127779874024702010.1038/s41563-025-02212-y