Interfacial mild alkalinity shapes Neutrophil immunometabolism through sphingolipid remodeling to enhance antibacterial host defense.

Implant-associated infection is commonly addressed by surfaces designed for direct bacterial killing, yet early host immune events at the implant interface are critical for infection outcome. Here, we designed Ti-A, a mildly alkaline titanium interface, to examine whether interfacial pH could act as an immune-regulatory cue for host-directed infection control. Ti-A showed acceptable cytocompatibility and promoted neutrophil extracellular traps (NETs) formation, thereby enhancing neutrophil-mediated killing of S. aureus. The attenuation of antibacterial activity after DNase I treatment supported the functional contribution of NETs. Metabolomic and molecular analyses further suggested that sphingolipid remodeling may converge on enhanced SPHK1-S1PR2/ROS signaling during Ti-A-induced NET formation. In a bacteria-loaded implant-induced bone defect model, Ti-A reduced local bacterial burden with evidence of NET-associated host defense at the infected interface. Importantly, this immune-antibacterial response did not compromise bone repair; Ti-A preserved osteogenic activity, promoted matrix mineralization, and improved infected bone defect repair without evident systemic toxicity. These findings identify mild interfacial alkalinity as a material-encoded cue that tunes neutrophil immunometabolism toward NET-mediated infection control while supporting subsequent bone regeneration.