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.
Keywords: Biomimetic scaffold; Bone regeneration; Cascade activation; Icariin delivery; One-step strategy.
© 2025 The Authors.