Guanidine-quaternary ammonium polymer-derived carbon dots differentially modulate bacterial respiration and osteoblast mitochondria to resolve infection and foster osteointegration.

Implant-associated infections (IAIs) represent one of the most challenging complications following orthopedic implantation. Current antibacterial strategies struggle to achieve complete pathogen eradication while maintaining sustained osteogenic activity at the implant-bone interface. Leveraging the spatial divergence in energy metabolism between prokaryotic and eukaryotic cells, we designed and synthesized guanidine-quaternary ammonium polymer-derived carbon dots (GQCDs) with confirmed structure. Under non-infected conditions, GQCDs enhance mitochondrial metabolism to promote bone regeneration. In infected microenvironments, GQCDs not only selectively target bacterial membranes and inhibit the respiratory chain to exert potent antibacterial effects, but also downregulate host inflammatory responses and restore mitochondrial function in osteoblasts, thereby creating a favorable microenvironment for bone repair. GQCDs can be stably integrated onto various clinical implant substrates via a coating process. GQCDs-coated implants possessed the dual antibacterial and osteogenic functionalities, which were validated using in vitro co-culture systems and in vivo implant infection models in rats and beagles, offering a promising strategy with encouraging translational prospects to address IAIs.