Synergistic dual Ag/Cu ion implantation to enhance antimicrobial defense on boston keratoprosthesis

Abstract

The Boston keratoprosthesis (BKPro) is a critical device for vision restoration in complex cases of corneal blindness, although its long-term retention is challenged by infection risks. This study aims to enhance the antimicrobial properties of the titanium (Ti) backplate of the BKPro by ion implanting silver and copper ions to achieve effective infection control while maintaining cytocompatibility. Research on antimicrobial modifications for BKPro is limited, and while metallic ions like Ag and Cu show promise for biomaterial improvement, their effects on human corneal keratocytes (HCKs) require further study. Ag and Cu were implanted onto rough Ti surfaces, as mono- and coimplantations. Cytotoxicity was assessed in HCKs, and antimicrobial efficacy was tested against Pseudomonas aeruginosa and Candida albicans. After 21 d, monoimplanted Ag samples released 300.4 ppb of Ag+, coimplanted samples released 427.5 ppb of Ag+ and 272.3 ppb of Cu ions, and monoimplanted Cu samples released 567.0 ppb of Cu ions. All ion-implanted surfaces supported HCK proliferation, exhibited no cytotoxicity, and showed strong antimicrobial activity. Ag-implanted surfaces provided antibacterial effects through membrane disruption and reactive oxygen species generation, while Cu-implanted surfaces exhibited antifungal effects via impaired enzymatic functions and reactive oxygen species. Coimplanted AgCu surfaces demonstrated synergistic antimicrobial effects, resulting from the synergy between the bactericidal actions of Ag and the oxidative stress contributions of Cu. Additionally, ion-implanted surfaces enhanced HCK adhesion under co-culture conditions. In conclusion, ion implantation effectively imparts antimicrobial properties to the Ti backplate of BKPro, reducing infection risks while preserving compatibility with corneal cells.