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    In vivo response to biodegradable controlled antibiotic release systems
    (John Wiley & Sons Inc, 2001) Korkusuz, F.; Korkusuz, P.; Ekşioğlu, F.; Gürsel, I.; Hasirci, V.
    In this study, the major goal was to evaluate in vitro and in vivo findings by macroscopy, radiology, and histology to determine the effectiveness of therapy of experimental implant-related osteomyelitis with antibiotic carrier rods constructed of microbial polyesters. The polymers used were poly(3-hydroxybutyrate-co-4-hydroxyvalerate) [P(3HB-co-4-HB)] and poly(3-hydroxybutyrate-co-3-hydroxy-valerate) [P(3-HB-co-3-HV)]. Both the Sulperazone(R) and the Duocid(R)-P(3-HB-co-4-HB) rods with a drug to polymer ratio of 1:1 (w/w) were effective in treating the bone infection that was experimentally initiated by inoculation of a hemolytic strain of Staphylococcus aureus (coagulase positive; phage type 52/52b) together with metal implants into the medullary area of rabbit tibia. Macroscopical data revealed that the effectiveness of therapy was apparent at week 6 for all categories tested. Radiological findings with Duocid(R)- and Sulperazone(R)-loaded P(3-HB-co-4-HB) rods improved significantly when judged by changes in periosteal elevation, widening of bone shaft, new bone formation, and soft-tissue deformation after 6 weeks of implantation. Histologically the signs of infection were found to subside by weeks 3 and 6. inflammatory cells were replaced with bone-forming cells upon treatment with Sulperazone(R)-P(3-HB-co-4-HB) and Duocid(R)-P(3-HB-co-4-HB). Osteoblastic activity was prominent. Intramedullary inflammation, although still present, started to be replaced by fibrous or bony tissue. Histological findings presented the subsidence of infection. In summary, the antibiotic-loaded biopolymeric rods appeared to have potential as a new controlled-release system for the treatment of implant related osteomyelitis and chronic osteomyelitis. (C) 2001 John Wiley & Sons, Inc.