The concept of local antibiotic delivery via biodegradable bone defect fillers with multifunctional properties for the treatment of bone infections is highly appealing. Fillers can be used to obliterate surgical dead space and to provide targeted local bactericidal concentrations in tissue for extended periods. Eventually, the osteoconductive component of the filler could guide the healing of the bone defect. The present experimental study was carried out to test this concept in a localized Staphylococcus aureus osteomyelitis model in the rabbit (n ‫؍‬ 31). A metaphyseal defect of the tibia was filled with a block of bone cement, followed by insertion of a bacterial inoculum. After removal of the bone cement and surgical debridement at 2 weeks, the defect was filled with a ciprofloxacin-containing (7.6% ؎ 0.1%, by weight) composite (treated-infection group) or with a composite without antibiotic (sham-treated group). Both a positive control group (untreated-infection group) and a negative control group were also produced.

No abstract

The use of local antibiotics from a biodegradable implant is appealing concept for treatment of chronic osteomyelitis. Our aim was to develop a new drug delivery system based on controlled ciprofloxacin release from poly(D/L-lactide). Cylindrical composite pellets (1.0 x 0.9 mm) were manufactured from bioabsorbable poly(D/L-lactide) matrix and ciprofloxacin (7.4 wt %). In vitro studies were carried out to delineate the release profile of the antibiotic and to verify its antimicrobial activity by means of MIC testing. A long-term study in rabbits was performed to validate the release of ciprofloxacin from the composite in vivo. Therapeutic level of ciprofloxacin (>2 microg/mL) was maintained between 60 and 300 days and the concentration remained below the potentially detrimental level of 20 microg/mL in vitro. The released ciprofloxacin had retained its antimicrobial properties against common pathogens. In an exploratory long-term in vivo study with three rabbits, ciprofloxacin could not be detected from the serum after moderate filling (160 mg) of the tibia (follow-up 168 days), whereas after high dosing (a total dose of 1,000 mg in both tibias) ciprofloxacin was found temporarily at low serum concentrations (14-34 ng/mL) during the follow-up of 300 days. The bone concentrations of ciprofloxacin could be measured in all samples at 168 and 300 days. The tested copolylactide matrix seems to be a promising option in selection of resorbable carriers for sustained release of antibiotics, but the composite needs modifications to promote ciprofloxacin release during the first 60 days of implantation.

This type of composition of implant may fulfill the requirements of bone infection therapy, for sustained local release of the selected antibiotic over several months.

The aim of this study was to compare the pullout forces of recently developed bioabsorbable ciprofloxacin-containing and plain self-reinforced polylactide/polyglycolide (SR-PLGA) miniscrews in human cadaver parietal bones. Parietal bone pieces (approximately 6 x 20 cm) were collected from five human male cadavers (44-75 years of age). Fifty plain SR-PLGA 80/20 miniscrews (diameter = 1.5 mm, length = 4.0 mm) and 50 ciprofloxacin-containing SR-PLGA 80/20 miniscrews (diameter = 1.5 mm, length = 4.0 mm) were used in this study. The force needed to pull the screws from human parietal cadaver bones was measured using a tensile strength-testing machine. The screw pullout speed was 10 mm/min. Means and SDs were calculated and analyzed using the Student t test (SPSS version 10.0 for Windows). The pullout forces of the ciprofloxacin-containing and plain miniscrews were 66.8 +/- 4.9 N and 96.3 +/- 9.3 N (significant difference, P < 0.001), respectively. The most common cause of failure was screw-shaft breakage (60% in the case of ciprofloxacin-containing screws and 52% in the case of plain SR-PLGA screws). Scanning electron microscopy showed that the fibrillar strip-like microstructure of plain SR-PLGA miniscrews turns into a coarse, uniaxial, platelet-like morphology in antibiotic SR-PLGA miniscrews as a result of the addition of ciprofloxacin. Ciprofloxacin-containing SR-PLGA screws consequently have a lower pullout strength than corresponding plain conventional SR-PLGA screws. Nevertheless, it is evident that the ciprofloxacin-containing screws can be applied in craniomaxillofacial surgery in nonload-bearing or slightly load-bearing applications.