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 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.
The cranial bone has a very limited regenerative capability. Patients with craniosynostosis (the premature fusion of cranial sutures, leading to skull abnormalities) often require extensive craniofacial reconstruction and repeated surgery. The possibility of grafting autologous osteoprogenitor cells seeded on bioabsorbable matrices is of great potential for inducing regeneration of craniofacial structure and protecting the brain from external insult. To this purpose we have studied the behaviour of normal and craniosynostotic mouse osteoblast cell lines, and of human primary osteoprogenitors from craniosynostotic patients. We have monitored their ability to grow and differentiate on plastic and on a scaffold composed of bioactive glass and bioabsorbable polymer by live fluorescent labelling and expression of bone differentiation markers. Cells from syndromic patients display a behaviour very similar to that observed in the stable mouse cell line we generated by introducing the human FGFR2-C278F, a mutation found in certain craniosynostosis, into MC3T3 osteblastic cells, indicating that the mutated cell line is a valuable model for studying the cellular response of human craniosynostotic osteoblasts. Both normal and mutated calvarial osteoprogenitors can attach to the bioactive scaffold, although mutated cells display adhesion defects when cultured on plastic. Furthermore, analysis of bone differentiation markers in human osteoblasts shows that the composite mesh, unlike PLGA(80) plates, supports bone differentiation. The ability of the mesh to support homing and differentiation in both normal and mutant osteoprogenitors is important, in view of further developing autologous biohybrids to repair cranial bone deficits also in craniosynostotic patients undergoing extensive reconstructive surgery.
The aim of this study was to assess tissue reactions to bioabsorbable self-reinforced ciprofloxacin-releasing polylactide/polyglycolide (SR-PLGA) 80/20 screws in rabbits' cranial bone. Two screws were implanted in each rabbit, one screw on either side of the sagittal suture (n = 28 rabbits). Animals were sacrificed after 2, 4, 8, 16, 24, 54 and 72 weeks, four animals per group. On histological examination the number of macrophages, giant cells, active osteoblasts and fibrous tissue layers were assessed and degradation of the screws was evaluated. At 2 weeks, the highest number of macrophages and giant cells were seen near the heads of the screws. After 4 and 8 weeks, the number of giant cells decreased but that of macrophages decreased from 16 weeks and on. Screws were surrounded by fibrous tissue capsule that progressively was growing in thickness by time. Active osteoblasts were seen around the shaft of the screws with the highest number seen at 4 weeks postoperatively. At 16 weeks, compact fragmentation of the screw heads was seen with macrophages seen inside the screw matrices. After 24 weeks, no polarization of the screws was seen. After one year, PLGA screws had been replaced by adipose tissue, fibrous tissue and "foamy macrophages" which had PLGA particles inside them. After 1(1/2) years, the amount of biomaterial remaining had decreased remarkably. The particles of biomaterial were inside "foamy macrophages." Ciprofloxacin-releasing SR-PLGA 80/20 screws elicited a mild inflammatory reaction but did not interfere with osteoblast activity. No complications were seen when implanted in cranial bone of rabbit.
The aim of this study was to compare the pull-out forces of bioabsorbable polylactide/glycolide (PLGA) tacks and screws in human cadaver parietal bones. Parietal bone pieces (c. 6 cm x 20 cm) were collected from five human male cadavers (age range: 47-75 years). Forty-nine BioSorbPDX (self-reinforced [SR] PLGA 80/20) tacks (1.5-mm diameter, 4.0-mm length), 47 BioSorbPDX (SR-PLGA 80/20) screws (1.5-mm diameter, 4.0-mm length), and 46 LactoSorb (PLGA 82/18) screws (1.5-mm diameter, 4.0-mm length) were applied. The tacks were applied to drill holes using a special applicator gun (no tapping or tightening). The screws were applied to drill holes in the traditional way using tapping and tightening with a screwdriver. A tensile testing machine was used. All the implants were tested thus: the head of the implant was held by an aluminum jig, and the jig was pulled with wire until implant failure. The testing pull speed was 10 mm/min. Means and SDs were calculated, and the data were analyzed using ANOVA. The pull-out force of the tacks was 115.9 +/- 8.3 N, that of Lactosorb screws was 112.9 +/- 12.1 N, and that of Biosorb screws was 110.4 +/- 8.9 N (statistically insignificant difference between the three groups). The most common reason for failure in the case of tacks was barb breakage (55.1%); it was thread breakage in the case of BioSorb screws (66%) and stem split in the case of Lactosorb screws (56%). Tacks seem to have a similar, perhaps even a little better, holding power to cranial bone as screws and can hence be recommended for clinical application, as the procedure saves time and, consequently, costs.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.