Jyri Koort

Efficacy of Ciprofloxacin-Releasing Bioabsorbable Osteoconductive Bone Defect Filler for Treatment of Experimental Osteomyelitis Due to Staphylococcus aureus

ABSTRACT 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. The treatment response, monitored by positron emission tomography (PET) with fluorine-18-labeled fluorodeoxyglucose ([18F]FDG) at 3 and 6 weeks, showed rapidly decreasing amounts of [18F]FDG uptake in the treated-infection group (P = 0.001 compared with the results for the untreated-infection group at 6 weeks). The bacteriological analysis confirmed the eradication of the bone pathogen in the treated-infection group. However, three animals had culture-positive soft tissue infections. All animals in the sham-treated and untreated-infection groups had culture-positive bone infections with typical radiographic changes of osteomyelitis. Histomorphometry, peripheral quantitative computed tomography, and backscattered electron imaging of scanning electron microscopy images verified the osteoconductive properties of the bioactive glass microspheres within the composite. The median bone ciprofloxacin concentrations were 1.2 and 2.1 μg/g at two anatomic locations of the tibia. This is the first report to show the value of [18F]FDG PET for quantitative monitoring of the treatment response in bone infections. The collaborative results of bacteriologic and [18F-FDG] PET studies showed that use of the multifunctional composite was successful for eradication of the S. aureus pathogen from bone.

Sustained release of ciprofloxacin from an osteoconductive poly(DL)-lactide implant.

Background and purpose Antibiotic-releasing bioresorbable implants are used for local treatment of bone infections, but most drug delivery systems release antibiotic for too short a time. Methods We used pellets (0.9 × 1.0 mm) made of bioabsorbable poly(DL) lactic acid matrix, ciprofloxacin (7.3 ± 0.4 wt%), and bioactive glass microspheres of 90–125 μm (29.3 ± 0.2 wt%). The ciprofloxacin release and antibacterial activity was measured in elution tests in vitro and local tissue concentrations were measured in rabbits. Results In elution tests in vitro, the therapeutic level (> 2 μg/mL) of ciprofloxacin was achieved within 6 h of the start of the test, and it was maintained for up to 300 days. The antibacterial activity of the antibiotic released from sterilized composites was similar to that of the unprocessed ciprofloxacin. In vivo measurements showed high local tissue concentrations (16-86 μg/g of bone tissue) for 3 months. Compared to previous experiments on two-component polymeric matrices (PLGA or PDLLA) with ciprofloxacin alone, adding bioactive glass microspheres into the composite resulted in morphological changes that facilitated fluid intrusion into the microstructure and quickened ciprofloxacin release. Interpretation 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.

Bioactive Glass Granules as Extender of Autogenous Bone Grafting in Cementless Intercalary Implant of the Canine Femur

Background and Aims: Ceramic bone graft substitutes have a potential to be used as replacement of allogeneic bone grafting and, under optimal distribution of particle size, they may even provide mechanical support. The current study examined the efficacy of bioactive glass granules as an extender of autogenous bone grafting in a segmental bone replacement model of the canine femur. Material and Method: A 16 mm long segment of the femur shaft was bilaterally replaced with an intercalary titanium implant in eight animals. The implant had cementless grooved proximal and distal stems. In one leg, the peri-implant space was packed with composite graft consisting of a mixture of bioactive glass granules and autogenous bone graft in proportion of 50:50. In the opposite leg, the peri-implant space was treated with autogenous bone graft alone. After surgery, unlimited functional loading was allowed. The outcome was evaluated at three months. Results: Eight out of sixteen autografted implants and seven out of sixteen composite-grafted implants were radiographically incorporated and clinically stable at three months. In the paired comparison, the proximal components of composite-grafted implants showed lower maximum load under torsional testing (p=0.068), less new bone in the longitudinal grooves of the stems (p=0.036) and lower affinity of new bone to implant surface (p=0.046). The distal components of the two sides showed a similar trend for less new bone in the grooves and lower bone affinity of new bone in the distal composite-grafted components. Conclusions: The current study suggests that supplementation of periprosthetic bone graft with bioactive ceramic particles may not help to promote healing of cementless implants under high dynamic loading conditions.

Bioceramic inlays do not improve mechanical incorporation of grit-blasted titanium stems in the proximal sheep femur

The aim of the present study was to determine, if bioactive glass (BG) surface inlays improve osseointegration of titanium implants in the proximal femur of adult sheep. In simulation of uncemented primary stems (nine animals), only the proximal part of the implants was grit-blasted and three surface slots of the grit-blasted region were filled with sintered BG microspheres. Primary stems were implanted using press-fit technique. In revision stem simulation (eight animals), grit-blasting was extended over the whole implant and seven perforating holes of the stem were filled by sintered BG granules. Revision stems were implanted with a mixture of autogenous bone graft and BG granules. Comparison with solid partially or fully grit-blasted control stems implanted in the contralateral femurs was performed in the primary and revision stem experiments at 12 and 25 weeks, respectively. Implant incorporation was evaluated by torsional failure testing and histomorphometry. Only one-third of the primary stems anchored mechanically to bone. The revision stems incorporated better and the BG inlays of the revision stems showed ingrowth of new bone. However, there were no significant differences in the torsional failure loads between the stems with BG inlays and the control stems. In conclusion, surface BG inlays gave no measurable advantage in mechanical incorporation of grit-blasted titanium implants. Overall, the proximal sheep femur, characterized by minimal amount of cancellous bone and the presence of adipocytic bone marrow, seemed to present compromised bone healing conditions.