Periprosthetic joint infections follow 1-3% of arthroplasty surgeries, with the biofilm nature of these infections presenting a significant treatment challenge1. Prevention strategies include antibiotic-loaded bone cement; however, increases in cementless procedures means there is an urgent need for alternative local antimicrobial delivery methods2. A novel, ultrathin, silica-based sol-gel technology is evaluated in this research as an anti-infective coating for orthopaedic prosthetic devices, providing local antibiotic release following surgery. Reduction in clinically relevant microbial activity and biofilm reduction by antimicrobial sol-gel coatings, containing a selection of antibiotics, were assessed via disc diffusion and microdilution culture assays using the Calgary biofilm device3. Proliferation, morphology, collagen, and calcium production by primary bovine osteoblasts cultured upon antibiotic sol-gel surfaces were examined, and cytotoxicity evaluated using Alamar blue staining and lactate dehydrogenase assays. Concentrations of silica, calcium and phosphorus compounds within the cell layer cultured on sol-gel coatings and concentrations eluted into media, were quantified using ICP-OES. Furthermore, cellular phenotype was assessed using alkaline phosphatase activity with time in culture.Aim
Method
An increasing elderly population means joint replacement surgery numbers are projected to increase, with associated complications such as periprosthetic joint infections (PJI) also rising. PJI are particularly challenging due to antimicrobial resistant biofilm development on implant surfaces and surrounding tissues, with treatment typically involving invasive surgeries and systemic antibiotic delivery. Consequently, functionalisation of implant surfaces to prevent biofilm formation is a major research focus. This study characterises clinically relevant antimicrobials including gentamicin, clindamycin, daptomycin, vancomycin and caspofungin within a silica-based, biodegradable sol-gel coating for prosthetic devices. Antimicrobial activity of the coatings against clinically relevant microorganisms was assessed via disc diffusion assays, broth microdilution culture methods and the MBEC assay used to determine anti-biofilm activity. Human and bovine cells were cultured in presence of antimicrobial sol-gel to determine cytotoxicity using Alamar blue and antibiotic release was measured by LC-MS. Biodegradability in physiological conditions was assayed by FT-IR, ICP-MS and measuring mass change. Effect of degradation products on osteogenesis were studied by culturing mesenchymal stem cells in the presence of media in which sol-gel samples had been immersed. Antimicrobial-loaded coatings showed strong activity against a wide range of clinically relevant bacterial and fungal pathogens with no loss of activity from antibiotic alone. The sol-gel coating demonstrated controlled release of antimicrobials and initial sol-gel coatings showed no loss of viability on MSCs with gentamicin containing coatings. Current work is underway investigating cytotoxicity of sol-gel compositions against MG-63 cells and primary osteoblasts. This research forms part of an extended study into a promising antimicrobial delivery strategy to prevent PJI. The implant coating has potential to advance PJI infection prevention, reducing future burden upon healthcare costs and patient wellbeing.
The aim of this study was to develop a single-layer hybrid organic-inorganic sol-gel coating that is capable of a controlled antibiotic release for cementless hydroxyapatite (HA)-coated titanium orthopaedic prostheses. Coatings containing gentamicin at a concentration of 1.25% weight/volume (wt/vol), similar to that found in commercially available antibiotic-loaded bone cement, were prepared and tested in the laboratory for: kinetics of antibiotic release; activity against planktonic and biofilm bacterial cultures; biocompatibility with cultured mammalian cells; and physical bonding to the material (n = 3 in all tests). The sol-gel coatings and controls were then tested in vivo in a small animal healing model (four materials tested; n = 6 per material), and applied to the surface of commercially pure HA-coated titanium rods.Aims
Methods
Vancomycin is commonly added to acrylic bone cement during revision arthroplasty surgery. Proprietary cement preparations containing vancomycin are available but significantly more expensive. We investigated whether the antibiotic elution and mechanical strength of ‘home-made’ vancomycin containing bone cement was comparable to commercial vancomycin-impregnated cement. A total of 18 cement discs of constant size, containing either proprietary CopalG+V®; or ‘home-made’ CopalR+G® with vancomycin added by hand, were made. Each disc contained the same antibiotic quantities (0.5g gentamycin, 2g vancomycin) and was immersed in ammonium acetate buffer in a sealed container. Fluid from each container was sampled at eight time points over a two week period. The concentration of gentamicin and vancomycin in the fluid was analysed using high performance liquid chromatography mass spectrometry. The impact strength of each PMMA cement preparation was measured using a Charpy-type impact tester.Introduction
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