Titanium Implant With Histidine‑Modified Antimicrobial Peptide Exhibiting Acid‑Enhanced Bactericidal Activity and Promoted Osteointegration Against Peri‑Implant Infections

ABSTRACT Peri‐implantitis, driven by acidic bacterial biofilm, remains a leading cause of dental implant failure. Existing antimicrobial coatings often exhibit static, non‐selective activity, which can disrupt tissue integration and lose efficacy in acidic infectious microenvironments. Herein, we developed an intelligent titanium implant coating based on histidine‐modified antimicrobial peptides (AMPHn) that responded to pathological pH changes. Through a covalent grafting strategy utilizing a Cys‐terminated spacer, the optimized Ti‐AMPH13 demonstrated precise, rapid, and reversible switching of properties around the critical pH threshold of 6.6. This molecular‑scale switching activated a bactericidal “on” state under acidic conditions, eradicating >99% of key oral pathogens, including Staphylococcus aureus , Escherichia coli , Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis , whereas unmodified AMP coatings showed markedly reduced efficacy in this acidic setting. Importantly, the coating maintained a biocompatible “off” state at physiological pH, with excellent hemocompatibility and cytocompatibility. In a rat peri‑implant infection model, Ti‑AMPH13 significantly reduced bacterial load, attenuated inflammatory infiltration, promoted organized collagen deposition, and enhanced bone‐implant contact by 19.59‑fold. By transforming the acidic hallmark of infection into a precise therapeutic trigger, this self‐adaptive coating system enables on‐demand and acid‐enhanced antimicrobial action without compromising host tissue integration, offering a transformative strategy to prevent implant‐associated infections and secure long‐term clinical success.