Multifunctional polycaprolactone‐based composite fibers with icariin and glutathione for effective repair of critical‐sized bone defects

Abstract Healing of critical‐sized bone defects is often delayed by oxidative stress and inadequate vascularization. To address this challenge, we developed a multifunctional electrospun polycaprolactone‐based scaffold, functionalized with Icariin and Glutathione (PCL@GSH@ICA) to enhance bone regeneration. Glutathione is a strong scavenger of reactive oxygen species, and Icariin provided sustained osteo‐angiogenic cues. The scaffold was systematically characterized for morphology, mechanical performance, and drug release, and evaluated through cell experiments, animal experiments, and theoretical studies. The cell experiment under oxidative stress conditions revealed that the scaffold supports osteogenic differentiation, endothelial angiogenesis, and bone marrow stromal cell proliferation. Animal studies demonstrate that nearly complete closure of rat calvarial defects has been achieved by PCL@GSH@ICA after 12 weeks of treatment. Upregulation of osteogenic (RUNX2, OCN) and angiogenic (VEGF, CD31) markers was confirmed by quantitative real‐time polymerase chain reaction test. Density functional theory (DFT) analysis indicated a stable electronic structure, and molecular docking suggested favorable interactions of Icariin and Glutathione with osteogenic and angiogenic proteins. Generally, these findings establish PCL@GSH@ICA as a multifunctional, cell‐free scaffold that accelerates bone regeneration by integrating osteogenesis, angiogenesis, and redox regulation.