Elution kinetics of vancomycin and gentamicin from carriers and their effects on mesenchymal stem cell proliferation: an in vitro study

Abstract

BackgroundMusculoskeletal infections remain a major complication in orthopedic surgery. The local delivery of antibiotics provides the high levels required to treat an infection without systemic toxicity. However, the local toxicity of antibiotic carriers to the mesenchymal stem cells, as a result of both the peak concentrations and the type of carrier, may be significant.MethodsTo address this concern, the elution kinetics of vancomycin and gentamicin from several commercially available antibiotic carriers and several carriers impregnated by a surgeon (10 ml of each sterile carrier were manually mixed with a 500 mg vancomycin and an 80 mg gentamicin solution, and the duration of impregnation was 30 min) were assessed. Moreover, the effects of these antibiotic carriers on stem cell proliferation were investigated. The following two types of stem cells were used: bone marrow and dental pulp stem cells.ResultsThe high eluted initial concentrations from antibiotic impregnated cancellous allogeneic bone grafts (which may be increased with the addition of fibrin glue) did not adversely affect stem cell proliferation. Moreover, an increased dental pulp stem cell proliferation rate in the presence of antibiotics was identified. In contrast to allogeneic bone grafts, a significant amount of antibiotics remained in the cement. Despite the favorable elution kinetics, the calcium carriers, bovine collagen carrier and freeze-dried bone exhibited decreased stem cell proliferation activity even in lower antibiotic concentrations compared with an allogeneic graft.ConclusionsThis study demonstrated the benefits of antibiotic impregnated cancellous allogeneic bone grafts versus other carriers.

Current Insights in the Application of Bone Grafts for Local Antibiotic Delivery in Bone Reconstruction Surgery

“…These concentrations exceeded the MIC of S. aureus 30. Similar elution kinetics of gentamicin and vancomycin were found in another study comparing freeze-dried and fresh frozen bone grafts 31…”

“…Moreover, in contrast to allogeneic bone grafts, a significant amount of antibiotics remained in the cement. 31…”

“…Noteworthy, proliferation can also be influenced by the carrier, independent of antibiotic loading; freeze-dried bone decreased proliferation of mesenchymal stem cells as compared to fresh-frozen grafts 31…”

“…A lyophilized bone graft can be conserved long-term at room temperature and is less antigenic 67. No significant difference was found in elution profile of gentamycin and vancomycin between impregnated morselized bone and freeze-dried bone powder 31. This is in contrast to the claim that bone marrow removal and freeze drying dramatically increases antibiotic uptake capability 28…”

Does the Effectiveness and Mechanical Strength of Kanamycin-Loaded Bone Cement in Musculoskeletal Tuberculosis Compare to Vancomycin-Loaded Bone Cement

“…Also, several additional factors, including methods of ALBC preparation and mixing, dose and molecular weight of antibiotics, products of bone cement, contribute to produce differences of porosity [26,34,47e49]. Because of the lack of information about the mechanical properties of kanamycin-loaded bone cement, comparison with vancomycin-loaded bone cement might provide reliable information because vancomycin has been already investigated in various settings for experiments and clinical experiences [19,21,22,24,31,36,48,50]. There were several weaknesses of this study.…”