Disruption of Sulfur Metabolism and Redox Homeostasis in Staphylococcus aureus Using Mechanically Robust Antibiofilm Ti‐Bi Alloys

Abstract Biofilm formation plays a pivotal role in implant‐associated infections, a persistent and significant challenge in post‐orthopedic surgical management. Given the essential role of sulfur metabolism in biofilm formation, and building upon the previous findings demonstrating bismuth's (Bi) potent capacity for intracellular hydrogen sulfide (H ₂ S) depletion, it is hypothesized that bismuth integration can confer anti‐infective properties to orthopedic implants. This study selected titanium (Ti) and Bi as alloying elements to prepare the Ti–Bi binary alloy system. Structural and electrochemical analyses confirmed the alloy's mechanical robustness and corrosion resistance. In vitro analyses revealed potent inhibition of biofilm formation by the alloys, with bismuth exerting dual antimicrobial mechanisms: 1) disruption of bacterial sulfur metabolism via sequestration of endogenous H ₂ S, and 2) competitive binding to key oxidoreductases, collectively destabilizing bacterial redox homeostasis. Proteomic profiling confirmed bismuth‐mediated downregulation of biofilm‐associated proteins. In vivo models validated infection mitigation in osteomyelitis. This study presents bismuth‐doped alloy system with robust antibiofilm efficacy, mechanical durability, and biocompatibility. These findings propose a novel strategy for engineering infection‐resistant orthopedic implants, offering translational frameworks for future material design.