3D‐Printed Biodegradable Zn‐Li‐Ag Porous Scaffolds Promote Infected Bone Regeneration by Alleviating Inflammation via Gbp2 Suppression

ABSTRACT Recurrent infections and persistent inflammation pose significant challenges in the clinical treatment of infected bone defects. Here, a porous scaffold of Zn‐0.8Li‐0.5Ag with a TPMS‐Gyroid structure was fabricated by laser powder bed fusion (LPBF) for the treatment of infected bone defects, integrating mechanical performance, anti‐infective properties, and osteogenic requirements. In vitro, Zn‐0.8Li‐0.5Ag scaffold exhibits potent bactericidal property against Staphylococcus aureus ( S. aureus ) and Escherichia coli ( E. coli ), excellent anti‐inflammatory property through immunomodulation, and acceptable osteogenesis property by enhancing the expression of osteogenesis‐related genes. In vivo, the Zn‐0.8Li‐0.5Ag scaffold significantly suppresses pathogenic bacteria, alleviates local inflammation, and promotes tissue regeneration. RNA sequencing further elucidated that the Zn‐0.8Li‐0.5Ag scaffold exerted anti‐inflammatory effects by releasing Zn 2 + , Li + , and Ag + , which downregulated Gbp2 expression, thereby inhibiting inflammatory pathways. Collectively, the Zn‐0.8Li‐0.5Ag scaffold with antibacterial, anti‐inflammatory, and osteogenic effects holds great promise as a promising biomaterial for repairing infectious bone defects.