Virulence-Selective Trap–Capture–Kill Antibacterial Nanostructures With Immune–Metabolic Regulation for Treating Implant-Associated Infections

The treatment of orthopedic implant–associated infections (IAIs) presents significant challenges due to increasing drug resistance. This study reports a virulence-selective trap–capture–kill antibacterial system for effectively treating persistent infections while promoting local bone tissue regeneration by regulating disordered immune and metabolic microenvironments caused by IAIs. Here, this work fabricates a nanostructured antibacterial system (F-14-TNA) based on a TiO 2 nanotube array modified with a cationic pentacyclic coplanar backbone, fascaplysin derivative 14 (F-14). The modified surface induces a unique virulence-initiated chemotaxis behavior, with the TiO 2 nanostructure selectively trapping hyperpathogenic bacterial strains from the infecting microbiota. These trapped bacterial strains are subsequently captured by the positively charged F-14 surface via electrostatic force. The virulence-selective bacteria are then killed via a reactive oxygen species–mediated pathway regulated by the phosphotransferase system cyclic adenosine monophosphate receptor protein cascade. In vitro and in vivo studies reveal that F-14-TNA has multiple biocompatibility functions, such as effective antibacterial activity, regulation of the immune microenvironment of bone infections, and recovery of disordered bone metabolism. The nanostructure developed in this study provides a novel approach for the treatment of IAIs.