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.

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 x 1.0 mm) made of bioabsorbable poly(DL) lactic acid matrix, ciprofloxacin (7.3 +/- 0.4 wt%), and bioactive glass microspheres of 90-125 microm (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 microg/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 micrg/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.

In vitro and in vivo testing of bioabsorbable antibiotic containing bone filler for osteomyelitis treatment.

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.

Efficacy of ciprofloxacin-releasing bioabsorbable osteoconductive bone defect filler for treatment of experimental osteomyelitis due to Staphylococcus aureus.

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 microg/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.

Comparative 18F-FDG PET of experimental Staphylococcus aureus osteomyelitis and normal bone healing.

UNLABELLED: PET using (18)F-FDG is a promising imaging modality for bone infections, based on intensive consumption of glucose by mononuclear cells and granulocytes. The method may have limitations in distinguishing uncomplicated bone healing from osteomyelitis. Bone healing involves an inflammatory phase that represents a highly activated state of cell metabolism and glucose consumption, mimicking infection on PET images. This laboratory study of a standardized model was designed to compare the (18)F-FDG PET characteristics of normal bone healing with those of local osteomyelitis. METHODS: A localized osteomyelitis model of the rabbit tibia was created by modifying a previously reported canine model. In the osteomyelitic group (n = 8), a standardized metaphyseal defect of the proximal right tibia was surgically created and filled with a block of orthopedic bone cement, followed by injection of a predetermined amount (0.1 mL) of Staphylococcus aureus (strain 52/52A/80, 1 x 10(5)/mL) into the space around the cement. The control group of animals with normal bone healing (n = 8) underwent the same procedure, but the bacterial injection was replaced by a sterile saline injection. The bone cement was surgically removed during debridement at 2 wk. Osteomyelitis was confirmed with positive bacterial cultures during the debridement and 6 wk later at the time of sacrifice. (18)F-FDG PET and peripheral quantitative CT were performed 3 and 6 wk after the debridement. The presence of osteomyelitic bone changes on plain radiographs was classified according to a previously published system. RESULTS: Before surgery, the standardized uptake values of (18)F-FDG did not differ markedly between the right and left tibias. In the control animals, uncomplicated bone healing was associated with a temporary increase in (18)F-FDG uptake at 3 wk (P = 0.007), but it returned almost to normal by 6 wk. In the experimental animals, localized osteomyelitis resulted in an intense continuous uptake of (18)F-FDG, which was higher than that of healing and intact bones at 3 wk (P = 0.014 and P < 0.001, respectively) and at 6 wk (P < 0.001). CONCLUSION: (18)F-FDG PET seems to be an efficient tool in the differentiation of uneventful bone healing from bone healing complicated by localized osteomyelitis.

Precision measurements of the RSA method using a phantom model of hip prosthesis.

Radiostereometric analysis (RSA) has become one of the recommended techniques for pre-market evaluation of new joint implant designs. In this study we evaluated the effect of repositioning of X-ray tubes and phantom model on the precision of the RSA method. In precision measurements, we utilized mean error of rigid body fitting (ME) values as an internal control for examinations. ME value characterizes relative motion among the markers within each rigid body and is conventionally used to detect loosening of a bone marker. Three experiments, each consisting of 10 double examinations, were performed. In the first experiment, the X-ray tubes and the phantom model were not repositioned between one double examination. In experiments two and three, the X-ray tubes were repositioned between one double examination. In addition, the position of the phantom model was changed in experiment three. Results showed that significant differences could be found in 2 of 12 comparisons when evaluating the translation and rotation of the prosthetic components. Repositioning procedures increased ME values mimicking deformation of rigid body segments. Thus, ME value seemed to be a more sensitive parameter than migration values in this study design. These results confirmed the importance of standardized radiographic technique and accurate patient positioning for RSA measurements. Standardization and calibration procedures should be performed with phantom models in order to avoid unnecessary radiation dose of the patients. The present model gives the means to establish and to follow the intra-laboratory precision of the RSA method. The model is easily applicable in any research unit and allows the comparison of the precision values in different laboratories of multi-center trials.

Biologic significance of surface microroughing in bone incorporation of porous bioactive glass implants.

A novel chemical etching method was recently developed to create a controlled microrough surface on porous bioactive glass implants. Our earlier in vitro studies showed enhanced attachment of osteoblast-like MG63 cells on a microrough bioactive glass surface. The purpose of our current study was to confirm the in vivo significance of surface microroughening for bone bonding of bioactive glass. Porous bioactive glass cones made of sintered microspheres were surgically implanted in the anterior cortex of rabbit femurs. Peripheral quantitative computed tomography (pQCT), biomechanical push-out testing, histomorphometry, and electron microscopy (BEI-SEM) were used to analyze bone ingrowth and osseointegration at 7, 10, 14, 28, 56, and 84 days after implantation. The results showed that microroughening of the bioactive glass surface significantly enhanced the bone-bonding response of the biomaterial. The positive response was seen in one of the three bioactive glass compositions studied. The affinity index of new bone on the glass surface was significantly (p = 0.02) increased with a trend (p = 0.10) toward improved mechanical incorporation. New bone formation was dependent on the glass composition, and it was found to occur not only through the mechanism of bone ingrowth but also based on in situ osteogenesis within implant interstices. Based on these results, the procedure of microroughening could enhance the osteopromotive properties of certain bioactive glass compositions.