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

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.