title: A chlorhexidine-releasing epoxy-based coating on titanium implants prevents Staphylococcus aureus experimental biomaterial-associated infection.
abstract: Prevention of biomaterial-associated infections (BAI) remains a challenging problem, in particular due to the increased risk of resistance development with the current antibiotic-based strategies. Metallic orthopaedic devices, such as non-cemented implants, are often inserted under high mechanical stress. These non-cemented implants cannot be protected by e.g. antibioticreleasing bone cement or other antimicrobial approaches, such as the use of bioactive glass. Therefore, in order to avoid abrasion during implantation procedures, we developed an antimicrobial coating with great mechanical stability for orthopaedic implants, to prevent Staphylococcus aureus BAI. We incorporated 5 and 10 wt % chlorhexidine in a novel mechanically stable epoxy-based coating, designated CHX5 and CHX10, respectively. The coatings displayed potent bactericidal activity in vitro against S. aureus, with over 80 % of the release (19 µg/cm2 for CHX5 and 41 µg/cm2 for CHX10) occurring within the first 24 h. In mice, the CHX10 coating significantly reduced the number of CFU (colony forming units), both on the implants and in the peri-implant tissues, 1 d after S. aureus challenge. The CHX10-coated implants were well-tolerated by the animals, with no signs of toxicity observed by histological analysis. Moreover, the coating significantly reduced the frequency of culture-positive tissues 1 d, and of culture-positive implants 1 and 4 d after challenge. In summary, the chlorhexidine-releasing mechanically stable epoxy-based CHX10 coating prevented implant colonisation and S. aureus BAI in mice and has good prospects for clinical development.
authors.forename: M
authors.initials: M
authors.lastname: Riool
authors.forename: A J
authors.initials: AJ
authors.lastname: Dirks
authors.forename: V
authors.initials: V
authors.lastname: Jaspers
authors.forename: L
authors.initials: L
authors.lastname: de Boer
authors.forename: T J
authors.initials: TJ
authors.lastname: Loontjens
authors.forename: C M
authors.initials: CM
authors.lastname: van der Loos
authors.forename: S
authors.initials: S
authors.lastname: Florquin
authors.forename: I
authors.initials: I
authors.lastname: Apachitei
authors.forename: L N
authors.initials: LN
authors.lastname: Rijk
authors.forename: H A
authors.initials: HA
authors.lastname: Keul
authors.affiliation: Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ, Amsterdam, The Netherlands.s.a.zaat@amc.uva.nl.
authors.forename: S A
authors.initials: SA
authors.lastname: Zaat
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use; D001672:Biocompatible Materials / Q000009:adverse effects*; D001706:Biopsy; D002710:Chlorhexidine / Q000494:pharmacology / Q000627:therapeutic use*; D020099:Coated Materials, Biocompatible / Q000737:chemistry*; D065546:Drug Liberation; D004852:Epoxy Compounds / Q000737:chemistry*; D008810:Mice, Inbred C57BL; D019736:Prostheses and Implants / Q000382:microbiology*; D016459:Prosthesis-Related Infections / Q000188:drug therapy / Q000382:microbiology / Q000517:prevention & control*; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000382:microbiology / Q000517:prevention & control*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000502:physiology*; D014025:Titanium / Q000737:chemistry*
chemical_list: D000900:Anti-Bacterial Agents; D001672:Biocompatible Materials; D020099:Coated Materials, Biocompatible; D004852:Epoxy Compounds; D014025:Titanium; D002710:Chlorhexidine