Although progress is evident in the effective treatment of joint replacement-related infections, it still remains a serious issue in orthopedics. As an example, the local application of antibiotics-impregnated bone grafts supplies the high drug levels without systemic side effects. However, antibiotics in the powder or solution form could be a risk for local toxicity and do not allow sustained drug release. The present study evaluated the use of an antibiotic gel, a water-in-oil emulsion, and a PLGA microparticulate solid dispersion as depot delivery systems impregnating bone grafts for the treatment of joint replacement-related infections. The results of rheological and bioadhesive tests revealed the suitability of these formulations for the impregnation of bone grafts. Moreover, no negative effect on proliferation and viability of bone marrow mesenchymal stem cells was detected. An ex vivo dissolution test of vancomycin hydrochloride and gentamicin sulphate from the impregnated bone grafts showed a reduced burst and prolonged drug release. The PLGA-based formulation proved to be particularly promising, as one-day burst release drugs was only 15% followed with sustained antibiotics release with zero-order kinetics. The results of this study will be the basis for the development of a new product in the Tissue Section of the University Hospital for the treatment of bone defects and infections of joint replacements.

• Keywords
• PLGA, biocompatibility, bone graft, cell culture, drug delivery, hydrogel, local antibiotic, water-in-oil emulsion,
• MeSH
• Anti-Bacterial Agents pharmacology   therapeutic use   MeSH
• Arthroplasty, Replacement * MeSH
• Emulsions MeSH
• Gentamicins MeSH
• Drug Delivery Systems MeSH
• Humans MeSH
• Powders MeSH
• Hematopoietic Stem Cell Transplantation * MeSH
• Vancomycin MeSH
• Water MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Anti-Bacterial Agents MeSH
• Emulsions MeSH
• Gentamicins MeSH
• Powders MeSH
• Vancomycin MeSH
• Water MeSH

BACKGROUND: Musculoskeletal 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. METHODS: To 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. RESULTS: The 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. CONCLUSIONS: This study demonstrated the benefits of antibiotic impregnated cancellous allogeneic bone grafts versus other carriers.

• Keywords
• Local antibiotic carriers, Musculoskeletal infections, Stem cells,
• MeSH
• Anti-Bacterial Agents administration & dosage   pharmacokinetics   MeSH
• Gentamicins administration & dosage   pharmacokinetics   MeSH
• Kinetics MeSH
• Cohort Studies MeSH
• Horses MeSH
• Bone Cements pharmacokinetics   MeSH
• Humans MeSH
• Mesenchymal Stem Cells drug effects   metabolism   MeSH
• Drug Carriers administration & dosage   pharmacokinetics   MeSH
• Cell Proliferation drug effects   physiology   MeSH
• Vancomycin administration & dosage   pharmacokinetics   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Anti-Bacterial Agents MeSH
• Gentamicins MeSH
• Bone Cements MeSH
• Drug Carriers MeSH
• Vancomycin MeSH