The Research Of Controlled Release And Bone Repair In The Materials For The Treatment Of Infected Bone Defects

Objective:To explore applications of the silk fibroin as an aqueous coating material for vancomycin-loaded Poly (s-caprolactone) (PCL) microspheres, and investigate the effects of silk coating on in vitro drug release.Methods:Vancomycin loaded PCL microspheres were prepared by a modification of the W1/O/W2 solvent extraction/evaporation procedure. During the preparation process the external phase was saturated or not by sodium chloride salt. Silk solutions used for coating were prepared by diluting the stock silk solution with deionized (DI) water to concentrations of 0.1%,0.5% and 1%(w/v), and silk coating was performed on the surface of PCL microspheres. Examinations of particle size analyses, vancomycin content, fourier transform infrared spectroscopy, differential scanning calorimetry, scanning electron microscopy and in vitro drug release were performed.Results:Size distributions of microspheres were found to be unimodal. Microsphere size in the blank PCL microspheres increased slightly, but there were no statistical differences in median particle size and mean particle size among blank PCL microspheres and vancomycin loaded PCL microspheres processed with or without NaCl (P>0.05). When sodium chloride was introduced into the external phase, the drug loading was observed with 75±1.61% of encapsulated vancomycin, whereas encapsulation efficiency was only 12±0.93% when the external phase was not saturated. The characteristic peaks of PCL and vancomycin, all appear in the DSC and FTIR of vancomycin loaded PCL microspheres. No appreciable shift of this peak was observed. The SEM observations indicate that the saturation of the external phase prevents the formation of large pores on microspheres surface. With this formulation, the microspheres have a round shape and present tiny pores. After coating with the 0.1% silk fibroin the microspheres had a similar size but exhibited a smooth, constant coating with no observed defects or cracks. Examination of the microspheres coating with 0.5% and 1% silk fibroin by scanning electron microscopy (SEM) revealed poor coating comprised of numerous surface defects and cracks in the film structure. The initial burst release in the microspheres coated with 0.1% SF reduced significantly, only about 24% of the encapsulated drugs were released in the first 24h, and duration of release extended to 33d.Conclusion:Silk fibroin can be considered as a potential aqueous film coating agent to be used for controlled release. Silk fibroin coating on vancomycin loaded PCL microspheres may be considered as an effective approach to prolong the drug release and improve the anti-infection effects. Objective:To confirm the composite scaffolds could be used as a vancomycin sustained-release system, and to investigate its efficiency in the treatment of chronic osteomyelitis in rabbit.Methods:Six kinds of vancomycin loaded scaffolds were prepared, including 6% gelatin,8% gelatin,10% gelatin (G-TCPO),10% gelatin/10%β-TCP (G-TCP1),10% gelatin/30%β-TCP (G-TCP3), and 10% gelatin/50%p-TCP (G-TCP5). Examinations of porosity analyses, mechanical test, fourier transform infrared spectroscopy and scanning electron microscopy were performed. All the vancomycin loaded scaffolds were transplanted intramuscularly in the dorsa of Sprague Dawley rats. Muscles near the implants were harvested in 3d,7d, 10d,14d,21d,28d,42d, and 56d after transplantation and the in vivo controlled release of vancomycin were measured. The implants were harvest in 2W,4W and 8W after implantation and the histological stains were performed to observe the degradation of the implants. After chronic Methicillin-resistant Staphylococcus aureus osteomyelitis models of rabbit were established, vacomycin loaded scaffolds including 10% gelatin,10% gelatin/10% P-TCP and 10% gelatin/30%β-TCP were implanted. X-ray and histological examinations were carried out.Results:There were no significant differences in the pore size of different scaffolds. And the porosity decreased with the increase of gelatin concentrations. Theβ-TCP granules were homogeneously localized in the gelatin walls of the composite scaffolds and the presence of the inorganic phase in the composite scaffolds affects both the porosity and interconnections. The compressive modulus of the vancomycin loaded scaffolds increased with the increase of gelatin concentration and theβ-TCP amount. The FTIR analysis supports that the process of scaffold preparation does not cause detectable changes in the chemical structure of vancomycin hydrochloride when incorporated. The release duration prolonged with the incease of gelatin concentrations. Vancomycin loaded composite scaffold of G-TCP5 showed a large initial burst effect and the total drug released out of scaffolds by day 21. The composite scaffolds of G-TCP1 and G-TCP3 showed a better controlled drug release, and the total drugs released within 42 days. The initial burst release in the composite scaffold of G-TCPO reduced significantly, and duration of release extended to 56d. Histological analysis revealed slow degradation in the scaffolds of high gelatin concentration and large amount ofβ-TCP. In the treatment of chronic MRSA osteomyelitis of rabbits, the G-TCP3 showed a better performace in the eliminating infections and bone defects repair.Conclusion:The composite scaffolds could achieve local therapeutic drug levels over an extended duration. And the gelatin with 30%p-TCP granules composite scaffold has optimal porosity, interconnection, mechanical properties and controlled release performances. It exibits good performaces in infection control and bone defects repair in the chronic MRSA osteomyelitis model.