One-step strategy for fabricating icariin-encapsulated biomimetic Scaffold: Orchestrating immune, angiogenic, and osteogenic cascade for enhanced bone regeneration.

The repair of bone defects relies on the intricate coordination of inflammation, angiogenesis, and osteogenesis. However, scaffolds capable of integrating osteo-immunomodulation and vascular-bone coupling to cascade-activate these processes remain a challenge. Here, a biomimetic scaffold (CHP@IC) with in situ PLGA@icariin (PLGA@IC) microspheres encapsulation was successfully fabricated using a one-step emulsification and polymerization strategy. This approach not only simplifies the fabrication process but also ensures high encapsulation efficiency and sustained release of IC through PLGA@IC microspheres. The findings from subcutaneous implantation, network pharmacology-predicted molecular targets, and in vitro studies collectively reveal that the CHP@IC-induced M2 polarization of macrophages via STAT3 signaling pathway triggers the sequential activation of inflammation, angiogenesis, and osteogenesis to enhance bone regeneration. The CHP@IC scaffold exhibited a significant osteogenic advantage in cranial defect repair, yielding new bone volumes approximately 3-fold and 10-fold greater than those in the CHP group and blank control group, respectively. This study not only elucidates the mechanism of IC in promoting regeneration of bone but also provides a novel method for designing scaffolds aimed at the efficient repair of bone defects.