Analysis of parameters influencing the release of antibiotics mixed with bone grafting material using a reliable mixing procedure.

Local infections arising from fracture fixation, defect reconstruction or joint replacement can cause extreme pain and impaired healing, lead to revision operations, prolong hospital stay and increase costs. Treatment options including prophylaxis are afforded by the use of grafts and biomaterials loaded with antibiotics. These can produce local therapeutic concentrations with a reduced systemic concentration and reduced systemic side-effects. Patient-specific loading of osteogenic graft materials with antibiotic could be an important option for orthopaedic surgeons. A local therapeutic concentration must be available for the desired duration and cytotoxic effects must be kept within an acceptable range. The present study investigates a simple and reliable mixing procedure that could be used for the perioperative combination of antibiotic powders and solutions with bone grafting materials. The potential influence of concentration and sampling regime on the release kinetics of gentamicin, tobramycin and vancomycin was studied over a period of 56days and potency and cytotoxicity were evaluated. In all treatment groups, gentamicin and tobramycin were completely released within 3days whilst vancomycin was released over a period of 14days. The results clearly show that the main parameter influencing release is the molecular weight of the drug. Growth of Staphylococcus aureus was inhibited in all 3 treatment groups for at least 3days. Cell viability and alkaline phosphatase activity of primary osteoblast-like cells were not significantly affected by the antibiotic concentrations obtained from the elution experiments. Bone grafting is an established component of surgery for bone defect filling and for biological stimulation of healing. Patient-specific enhancement of such procedures by incorporation of antibiotics for infection prevention or by addition of cytokines for promotion of impaired healing or for treatment of critical size defects will be a relevant issue in the future.