a, Schematic of microsphere template-based fabrication of ICC geometry polyacrylamide hydrogel scaffolds. Bright-field image shows ICC structure through transparent hydrogel matrix (top), and SEM images show interconnecting junctions and surface immobilized type I collagen (bottom). b, Confocal images of tiled top and cross-sectioned scaffolds demonstrate homogeneously seeded fluorescently labeled hBMSCs into 3D ICC hydrogel scaffolds with typical mesenchymal morphology after adhesion. c, Representative gross and histological images of subdermally implanted hBMSC seeded scaffold after 4 weeks in NSG mice. H&E (top) and trichrome staining (bottom) shows recruitment of stromal and immune cells, and organized collagen architecture, respectively. d, Immunohistostaining (IHS) of hVimentin and mCD31 for analyzing spatial characteristics of hBMSCs and vasculature within the scaffold. e, f, Quantitative analysis of blood vessels (e), and hBMSC localization (f) (n=3, independent scaffolds). g, Comparison of key human cytokine secretion from hBMSC-scaffolds before and after implantation for 4 and 12 weeks (n=3, independent scaffolds). Data are mean ± standard deviation (s.d.). *P < 0.05 via two-sided student t-test.