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

Soňa Kucharíková, Evelien Gerits, Katrijn De Brucker, Annabel Braem, Katerina Ceh, Gregor Majdič, Tanja Španič, Estera Pogorevc, Natalie Verstraeten, Helene Tournu, Nicolas Delattin, Frédéric Impellizzeri, Martin Erdtmann, Annika Krona, Maria Lövenklev, Miomir Knezevic, Mirjam Fröhlich, Jef Vleugels, Maarten Fauvart, Wander Jose De SilvaKatleen Vandamme, Jordi Garcia-Forgas, Bruno P.A. Cammue, Jan Michiels, Patrick Van Dijck, Karin Thevissen

Research output: Contribution to journalArticle

25 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)936-945
Number of pages10
JournalJournal of Antimicrobial Chemotherapy
Volume71
Issue number4
DOIs
StatePublished - Apr 1 2016

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Biofilms
Anti-Infective Agents
Titanium
Candida albicans
Immobilization
Staphylococcus aureus
caspofungin
Vancomycin
Osseointegration
Vancomycin Resistance
Biocompatible Materials
Infection
Mesenchymal Stromal Cells
Confocal Microscopy

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Microbiology (medical)
  • Infectious Diseases
  • Pharmacology (medical)

Cite this

Covalent immobilization of antimicrobial agents on titanium prevents Staphylococcus aureus and Candida albicans colonization and biofilm formation. / Kucharíková, Soňa; Gerits, Evelien; De Brucker, Katrijn; Braem, Annabel; Ceh, Katerina; Majdič, Gregor; Španič, Tanja; Pogorevc, Estera; Verstraeten, Natalie; Tournu, Helene; Delattin, Nicolas; Impellizzeri, Frédéric; Erdtmann, Martin; Krona, Annika; Lövenklev, Maria; Knezevic, Miomir; Fröhlich, Mirjam; Vleugels, Jef; Fauvart, Maarten; De Silva, Wander Jose; Vandamme, Katleen; Garcia-Forgas, Jordi; Cammue, Bruno P.A.; Michiels, Jan; Van Dijck, Patrick; Thevissen, Karin.

In: Journal of Antimicrobial Chemotherapy, Vol. 71, No. 4, 01.04.2016, p. 936-945.

Research output: Contribution to journalArticle

Kucharíková, S, Gerits, E, De Brucker, K, Braem, A, Ceh, K, Majdič, G, Španič, T, Pogorevc, E, Verstraeten, N, Tournu, H, Delattin, N, Impellizzeri, F, Erdtmann, M, Krona, A, Lövenklev, M, Knezevic, M, Fröhlich, M, Vleugels, J, Fauvart, M, De Silva, WJ, Vandamme, K, Garcia-Forgas, J, Cammue, BPA, Michiels, J, Van Dijck, P & Thevissen, K 2016, 'Covalent immobilization of antimicrobial agents on titanium prevents Staphylococcus aureus and Candida albicans colonization and biofilm formation', Journal of Antimicrobial Chemotherapy, vol. 71, no. 4, pp. 936-945. https://doi.org/10.1093/jac/dkv437
Kucharíková, Soňa ; Gerits, Evelien ; De Brucker, Katrijn ; Braem, Annabel ; Ceh, Katerina ; Majdič, Gregor ; Španič, Tanja ; Pogorevc, Estera ; Verstraeten, Natalie ; Tournu, Helene ; Delattin, Nicolas ; Impellizzeri, Frédéric ; Erdtmann, Martin ; Krona, Annika ; Lövenklev, Maria ; Knezevic, Miomir ; Fröhlich, Mirjam ; Vleugels, Jef ; Fauvart, Maarten ; De Silva, Wander Jose ; Vandamme, Katleen ; Garcia-Forgas, Jordi ; Cammue, Bruno P.A. ; Michiels, Jan ; Van Dijck, Patrick ; Thevissen, Karin. / Covalent immobilization of antimicrobial agents on titanium prevents Staphylococcus aureus and Candida albicans colonization and biofilm formation. In: Journal of Antimicrobial Chemotherapy. 2016 ; Vol. 71, No. 4. pp. 936-945.
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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.",
author = "Soňa Kuchar{\'i}kov{\'a} and Evelien Gerits and {De Brucker}, Katrijn and Annabel Braem and Katerina Ceh and Gregor Majdič and Tanja Španič and Estera Pogorevc and Natalie Verstraeten and Helene Tournu and Nicolas Delattin and Fr{\'e}d{\'e}ric Impellizzeri and Martin Erdtmann and Annika Krona and Maria L{\"o}venklev and Miomir Knezevic and Mirjam Fr{\"o}hlich and Jef Vleugels and Maarten Fauvart and {De Silva}, {Wander Jose} and Katleen Vandamme and Jordi Garcia-Forgas and Cammue, {Bruno P.A.} and Jan Michiels and {Van Dijck}, Patrick and Karin Thevissen",
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T1 - Covalent immobilization of antimicrobial agents on titanium prevents Staphylococcus aureus and Candida albicans colonization and biofilm formation

AU - Kucharíková, Soňa

AU - Gerits, Evelien

AU - De Brucker, Katrijn

AU - Braem, Annabel

AU - Ceh, Katerina

AU - Majdič, Gregor

AU - Španič, Tanja

AU - Pogorevc, Estera

AU - Verstraeten, Natalie

AU - Tournu, Helene

AU - Delattin, Nicolas

AU - Impellizzeri, Frédéric

AU - Erdtmann, Martin

AU - Krona, Annika

AU - Lövenklev, Maria

AU - Knezevic, Miomir

AU - Fröhlich, Mirjam

AU - Vleugels, Jef

AU - Fauvart, Maarten

AU - De Silva, Wander Jose

AU - Vandamme, Katleen

AU - Garcia-Forgas, Jordi

AU - Cammue, Bruno P.A.

AU - Michiels, Jan

AU - Van Dijck, Patrick

AU - Thevissen, Karin

PY - 2016/4/1

Y1 - 2016/4/1

N2 - 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.

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