Covalent immobilization of antimicrobial agents on titanium prevents Staphylococcus aureus and Candida albicans colonization and biofilm formation

Kucharikova, Sona; Gerits, Evelien; De Brucker, Katrijn; Braem, Annabel; Ceh, Katerina; Majdic, Gregor; Spanic, Tanja; Pogorevc, Estera; Verstraeten, Natalie; Tournu, Helene; Delattin, Nicolas; Impellizzeri, Frederic; Erdtmann, Martin; Krona, Annika; Lovenklev, Maria; Knezevic, Miomir; Frohlich, Mirjam; Vleugels, Jef; Fauvart, Maarten; de Silva, Wander Jose; Vandamme, Katleen; Garcia-Forgas, Jordi; Cammue, Bruno PA; Michiels, Jan; Van Dijck, Patrick; Thevissen, Karin

doi:10.1093/jac/dkv437

Covalent immobilization of antimicrobial agents on titanium prevents Staphylococcus aureus and Candida albicans colonization and biofilm formation

Author:

Kucharikova, Sona

Gerits, Evelien ; De Brucker, Katrijn ; Braem, Annabel ; Ceh, Katerina ; Majdic, Gregor ; Spanic, Tanja ; Pogorevc, Estera ; Verstraeten, Natalie ; Tournu, Helene ; Delattin, Nicolas ; Impellizzeri, Frederic ; Erdtmann, Martin ; Krona, Annika ; Lovenklev, Maria ; Knezevic, Miomir ; Frohlich, Mirjam ; Vleugels, Jef ; Fauvart, Maarten ; de Silva, Wander Jose ; Vandamme, Katleen ; Garcia-Forgas, Jordi ; Cammue, Bruno PA ; Michiels, Jan ; Van Dijck, Patrick ; Thevissen, Karin

Keywords:

Science & Technology, Life Sciences & Biomedicine, Infectious Diseases, Microbiology, Pharmacology & Pharmacy, ORTHOPEDIC IMPLANTS, ESCHERICHIA-COLI, IN-VITRO, INFECTIONS, CASPOFUNGIN, EPIDERMIDIS, STRATEGIES, MANAGEMENT, DIAGNOSIS, SURFACES, Animals, Anti-Bacterial Agents, Anti-Infective Agents, Antifungal Agents, Biofilms, Candida albicans, Caspofungin, Cell Line, Echinocandins, Female, Humans, Lipopeptides, Mice, Mice, Inbred BALB C, Osseointegration, Prostheses and Implants, Staphylococcus aureus, Titanium, Vancomycin, 0605 Microbiology, 1108 Medical Microbiology, 1115 Pharmacology and Pharmaceutical Sciences, 3202 Clinical sciences, 3214 Pharmacology and pharmaceutical sciences

Abstract:

OBJECTIVES: Biofilm-associated implant infections represent a serious public health problem. Covalent immobilization of antimicrobial agents on titanium (Ti), thereby inhibiting biofilm formation of microbial pathogens, is a solution to this problem. METHODS: Vancomycin (VAN) and caspofungin (CAS) were covalently bound on Ti substrates using an improved processing technique adapted to large-scale coating of implants. Resistance of the VAN-coated Ti (VAN-Ti) and CAS-coated Ti (CAS-Ti) substrates against in vitro biofilm formation of the bacterium Staphylococcus aureus and the fungal pathogen Candida albicans was determined by plate counting and visualized by confocal laser scanning microscopy. The efficacy of the coated Ti substrates was also tested in vivo using an adapted biomaterial-associated murine infection model in which control-Ti, VAN-Ti or CAS-Ti substrates were implanted subcutaneously and subsequently challenged with the respective pathogens. The osseointegration potential of VAN-Ti and CAS-Ti was examined in vitro using human bone marrow-derived stromal cells, and for VAN-Ti also in a rat osseointegration model. RESULTS: In vitro biofilm formation of S. aureus and C. albicans on VAN-Ti and CAS-Ti substrates, respectively, was significantly reduced compared with biofilm formation on control-Ti. In vivo, we observed over 99.9% reduction in biofilm formation of S. aureus on VAN-Ti substrates and 89% reduction in biofilm formation of C. albicans on CAS-Ti substrates, compared with control-Ti substrates. The coated substrates supported osseointegration in vitro and in vivo. CONCLUSIONS: These data demonstrate the clinical potential of covalently bound VAN and CAS on Ti to reduce microbial biofilm formation without jeopardizing osseointegration.