Spatiotemporally programming the immune-osteogenic cascade with a dual-immunomodulatory scaffold for functional bone regeneration

and protocatechualdehyde from nanoparticles enhances the immunoregulatory function of homing MSCs. Additionally, hydroxyapatite framework provides essential mechanical stability and ion sources for late-stage osteogenic mineralization. Single-cell RNA sequencing and validation demonstrate that DIBS effectively induces the generation of immunoregulatory MSC subpopulations, which is associated with M2 macrophage activation through CCL2/CCR2 signaling axis, promoting angiogenesis and osteogenic differentiation. In vivo, DIBS effectively remodels the osteoimmune microenvironment, induces organized collagen arrangement and H-type vascularization, facilitating functional bone tissue repair. This study provides a new multicellular immunomodulatory strategy for endogenous bone repair.