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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.

Purpose: Acrylates for bonding of joint prostheses and stainless-steel brackets in orthopedics and orthodontics are prone to bacterial adhesion and biofilm formation, respectively, leading to serious infectious complications. Here we describe the preparation of a contact-killing acrylic resin by incorporation of [3-(methacryloylamino)propyl] trimethylammonium chloride (MAPTAC)., Methods: Physicochemical properties of the acrylates with and without MAPTAC incorporated were determined with X-ray photoelectron spectroscopy and water contact angles. The bond-strength of the acrylate with different percentages of MAPTAC was determined in a shear mode. The efficacy in contact-killing of the acrylate with MAPTAC incorporated with and without an adsorbed salivary coating was evaluated for various oral streptococcal strains. Cytotoxicity was tested against human skin fibroblasts., Results: Acrylates with 16 wt% and 20 wt% incorporated MAPTAC showed strong contact-killing of various oral streptococcal strains up to challenge concentrations of 109 mL-1 within 15 min, with no elution of antimicrobial polymers. Contact-killing reduced after coating with a salivary conditioning film, but still remained significant up to a challenge concentration of 105 mL-1. No cytotoxicity of acrylate with incorporated MAPTAC was observed toward human skin fibroblasts. The bond strengths of stainless-steel brackets fixed to etched enamel through the resin (12 ± 3 MPa) decreased with increasing amounts MAPTAC to half of the original value when 20 wt% of MAPTAC was incorporated, which remained within a clinically acceptable range., Conclusions: These results suggest that MAPTAC can be effectively incorporated in orthodontic resin to provide long-term bactericidal activity against oral bacteria, with potential application in orthopedics.

Effects of a quaternary ammonium compound (QAC) on the survival of adhering staphylococci on a surface were investigated using atomic force microscopy (AFM). Four strains with different minimal inhibitory concentrations (MIC) and minimal bactericidal concentrations (MBC) for the QAC were exposed to three different concentrations of the QAC in potassium phosphate buffer (0.5×, 1×, and 2× MBC) while adhering to glass. Adhering staphylococci were repeatedly imaged with AFM in the contact mode, and the cell surface was found to wrinkle upon progressive exposure to the QAC until bacteria disappeared from the substratum. Higher concentrations of QAC yielded faster wrinkling and the disappearance of bacteria during imaging. Two slime-producing staphylococcal strains survived longer on the surface than two non-slime-producing strains despite similar MICs and MBCs. All staphylococci adhering in unscanned areas remained adhering during exposure to QAC. Since MICs and MBCs did not relate to bacterial cell surface hydrophobicities and zeta potentials, survival on the surface is probably not determined by the direct interaction of QAC molecules with the cell surface. Instead, it is suggested that the pressure of the AFM tip assists the incorporation of QAC molecules in the membrane and enhances their bactericidal efficacy. In addition, the prolonged survival under pressure from slime-producing strains on a surface may point to a new protective role of slime as a stress absorber, impeding the incorporation of QAC molecules. The addition of Ca(2+) ions to a QAC solution yielded longer survival of intact, adhering staphylococci, suggesting that Ca(2+) ions can impede the exchange of membrane Ca(2+) ions required for QAC incorporation.