fibrin and Osteomyelitis

At present, surgical debridement and systematic administration of antibiotics represent the mainstay of treatment for chronic osteomyelitis. However, it is now understood that Staphylococcus aureus (S. aureus) can survive within excessively polarized M2 macrophages and evade antibiotics, accounting for the high recurrence of chronic osteomyelitis. Effective treatments for intracellular infection have rarely been reported. Herein, we designed an in situ sprayed liposomes hydrogels spray with macrophage-targeted effects and the ability to reverse polarization and eradicate intracellular bacteria to reduce the recurrence of osteomyelitis. Resiquimod (R848)-loaded and phosphatidylserine (PS)-coating nanoliposomes were introduced into fibrinogen and thrombin to form the PSL-R848@Fibrin spray. Characterization and phagocytosis experiments were performed to confirm the successful preparation of the PSL-R848@Fibrin spray. Meanwhile, in vitro cell experiments validated its ability to eliminate intracellular S. aureus by reprogramming macrophages from the M2 to the M1 phenotype. Additionally, we established a chronic osteomyelitis rat model to simulate the treatment and recurrence process. Histological analysis demonstrated a significant increase in M1 macrophages and the elimination of intracellular bacteria. Imaging revealed a significant decrease in osteomyelitis recurrence. Overall, the liposome hydrogels could target macrophages to promote antibacterial properties against intracellular infection and reduce the recurrence of chronic osteomyelitis, providing the foothold for improving the outcomes of this patient population. STATEMENT OF SIGNIFICANCE: Chronic osteomyelitis remains a high recurrence although undergoing traditional treatment of debridement and antibiotics. S. aureus can survive within the excessively polarized M2 macrophages to evade the effects of antibiotics. However, few studies have sought to investigate effective intracellular bacteria eradication. Herein, we designed a macrophage-targeted R848-containing liposomes fibrin hydrogels spray (PSL-R848@Fibrin) that can reprogram polarization of macrophages and eradicate intracellular bacteria for osteomyelitis treatment. With great properties of rapid gelation, strong adhesion, high flexibility and fit-to-shape capacity, the facile-operated immunotherapeutic in-situ-spray fibrin hydrogels exhibited huge promise of reversing polarization and fighting intracellular infections. Importantly, we reveal

Topics: Animals; Anti-Bacterial Agents; Fibrin; Humans; Hydrogels; Liposomes; Osteomyelitis; Rats; Staphylococcal Infections; Staphylococcus aureus

The goal of our work was to study the changes in the bone tissue, bone marrow and surrounding tissues in animals during early stages of experimental osteomyelitis. Osteomyelitis was simulated in 30 infants rabbits aged 3-4 months whose body weight accounted 1200-1600 grams through the insertion of 5-6 million of aurococcus into the marrow channel of a shinbone. The study of bone marrow, bone tissue and surrounding tissue was conducted 30 minutes, 6, 12, 24, 48 and 60 hours after the contamination with the help of light and electronic (transmission and scanning) microscopy. It was proved that the first changes are characterized by the evident changes in the vessel's walls which cause the swelling of bone marrow and suppurative inflammation in the bone tissue occurs only in the end of the 3d day of the experiment. These data confirm the necessity of osteoperfortation during the first 24 hours of contamination in order to remove the swelling and to correct vessel disorders.

Topics: Animals; Body Weight; Bone and Bones; Bone Marrow; Disease Models, Animal; Fibrin; Microscopy, Electron, Scanning; Microscopy, Electron, Transmission; Osteomyelitis; Rabbits; Staphylococcal Infections; Time Factors

Bone defect complicated by infection remains a major challenge in orthopedic surguries, and bone grafting for primary repair often associates with high failure rate. The rapid progress in the research spectrums of tissue-engineered bone and antibiotic delivery systems bring hope to solve this issue. Herein, we evaluated the local anti-infective and osteogenic potential of an injectable anti-infection tissue-engineered construct, which includes a fibrin gel scaffold and vancomycin alginate beads (Vanco-AB) to form composites, in the treatment of chronic osteomyelitis with bone defect in rabbit tibia. The infected bone defect model of rabbit tibia was established. Then, the bone defects in the proximal tibial metaphysis were implanted with the constructed composites, containing different combinations of mesenchymal stem cells and Vanco-AB. The in vivo capacities of anti-infection and local osteogenesis of the grafts were determined using radiographic assessment, histopathological observation, and microorganism cultures. Results showed that the injectable anti-infection tissue-engineered construct, comprising a fibrin gel scaffold and Vanco-AB led to efficient eradication of bacteria. At 1 and 3 months after transplantation, the radiographic assessment and microbiological examination demonstrated that the sustained antibiotic release by Vanco-AB significantly decreased the Norden scores of osteomyelitis, generated negative results for the presence of bacteria, and reduced the relapse of osteomyelitis. Meanwhile, tissue-engineered construct implanted in one-stage promoted local bone repair and reconstruction, and it exhibited more apparent osteogenic potential, compared to the control group (without Vanco-AB). In conclusion, the current study achieved the primary repair of bone defect with infection, thus providing an alternative treatment strategy for infected bone defect, which occurs commonly in chronic osteomyelitis.

Topics: Animals; Anti-Infective Agents; Bone Substitutes; Combined Modality Therapy; Delayed-Action Preparations; Fibrin; Fracture Healing; Osteomyelitis; Rabbits; Tibia; Tibial Fractures; Tissue Scaffolds; Treatment Outcome; Vancomycin

Topics: Biopsy, Needle; Bone Marrow; Diagnosis, Differential; Egypt; Fever of Unknown Origin; Fibrin; Granuloma; Hepatitis; Humans; Liver; Liver Function Tests; Male; Middle Aged; Osteomyelitis; Q Fever; Travel

We prepared a composite of fibrin clot and ciprofloxacin for use as a biodegradable antibiotic delivery system with sustained effect for the treatment of chronic osteomyelitis. In vitro, ten experiments were performed in which 10 mg of ciprofloxacin were incorporated into 4 ml of fibrin clot. The clots were preserved in nutrient broth and incubated at 37 degrees C for a total of 60 days. Every 24 h a broth specimen was obtained, and the ciprofloxacin concentration was determined by microbiological assay. The maximum level of antibiotic was noted on the first day (49.9 +/- 5.1 mg/l). The ciprofloxacin-fibrin clot complexes usually disintegrated after 60 days. In vivo, the fibrin-ciprofloxacin clots were made as previously described. The composite was implanted in the medullary canal of rabbit tibiae, and the antibiotic concentration was measured in bone, muscle, skin and serum. In all tissues around the implant, the concentration of antibiotic exceeded the minimum inhibitory concentration against the common causative organisms of osteomyelitis for 10 days. The implant caused no systemic side-effects, and it is likely to prove clinically useful as a drug delivery system for treating chronic osteomyelitis.

Topics: Animals; Anti-Infective Agents; Biodegradation, Environmental; Chronic Disease; Ciprofloxacin; Drug Carriers; Drug Combinations; Drug Delivery Systems; Fibrin; Microbial Sensitivity Tests; Osteomyelitis; Rabbits; Tissue Distribution

Topics: Adult; Animals; Bone and Bones; Bone Cements; Bone Transplantation; Female; Femur; Fibrin; Humans; Ilium; Osteomyelitis; Osteotomy; Rabbits; Surgical Wound Infection; Transplantation, Autologous; Transplantation, Homologous