In vivo response to biodegradable controlled antibiotic release systems

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 carri er rods constructed of microbial polyesters. The polymers used were poly(3- hydroxybutyrate-co-4-hydroxyvalerate) [P(3HB-co-4-HB)] and poly(3-hydroxybu tyrate-co-3-hydroxy-valerate) [P(3-HB-co-3-HV)]. Both the Sulperazone(R) an d 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 i nitiated by inoculation of a hemolytic strain of Staphylococcus aureus (coa gulase positive; phage type 52/52b) together with metal implants into the m edullary area of rabbit tibia. Macroscopical data revealed that the effecti veness of therapy was apparent at week 6 for all categories tested. Radiolo gical findings with Duocid(R)- and Sulperazone(R)-loaded P(3-HB-co-4-HB) ro ds improved significantly when judged by changes in periosteal elevation, w idening of bone shaft, new bone formation, and soft-tissue deformation afte r 6 weeks of implantation. Histologically the signs of infection were found to subside by weeks 3 and 6. inflammatory cells were replaced with bone-fo rming 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 infl ammation, although still present, started to be replaced by fibrous or bony tissue. Histological findings presented the subsidence of infection. In su mmary, the antibiotic-loaded biopolymeric rods appeared to have potential a s a new controlled-release system for the treatment of implant related oste omyelitis and chronic osteomyelitis. (C) 2001 John Wiley & Sons, Inc.