PREVENTING PERIPROSTHETIC JOINT INFECTION: A NOVEL ANTIMICROBIAL SOL-GEL APPROACH

Aim Periprosthetic joint infections follow 1-3% of arthroplasty surgeries, with the biofilm nature of these infections presenting a significant treatment challenge 1 . Prevention strategies include antibiotic-loaded bone cement; however, increases in cementless procedures means there is an urgent need for alternative local antimicrobial delivery methods 2 . 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. Method 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 device 3 . 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. Results Low antibiotic concentrations within sol-gel had an inhibitory effect on clinically relevant biofilm growth, for example 0.8 mg ml -1 tobramycin inhibited clinically isolated S. aureus (MRSA) growth with an 8-log reduction in viable colony forming units. There was no significant difference in metabolic activity between untreated and sol-gel exposed primary bovine osteoblasts in elution-based assays. Reduction (2-fold) in metabolic activity in direct contact assays after 48 hours exposure was likely to be due to increased osteoinduction, whereas no impact upon cell proliferation were observed (p=0.92 at 14 days culture). The morphology of primary osteoblasts was unaffected by culture on sol-gel coatings and collagen production was maintained. Calcium containing nodule production within bovine osteoblastic cells was increased 16-fold after 14 days culture upon sol-gel. Conclusions The ultrathin sol-gel coating showed low cytotoxicity, strong biofilm reducing activity and antimicrobial activity, which was comparable to antibiotics alone, demonstrating that sol-gel delivery of antibiotics could provide local antimicrobial effects to inhibit PJI growth without the need for bone cement. Future work will develop and evaluate sol-gel performance in an ex vivo explant bone infection model which will reduce the need for animal experimentation.