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Evaluation of Controlled Drug Release Chitosan-based Coatings on Titanium Implants: Microstructure, Bioactivity and Biocompatibility

Ordikhani, Farideh | 2014

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  1. Type of Document: Ph.D. Dissertation
  2. Language: Farsi
  3. Document No: 46174 (07)
  4. University: Sharif University of Technology
  5. Department: Materials science and Engineering
  6. Advisor(s): Simchi, Abdolreza
  7. Abstract:
  8. Implant-associated infections are one of the most serious complications in orthopaedic and trauma surgery as it may result in poor functional outcome, implant failure, chronic osteomyelitis or even death. Great concerns have been taken to reduce implant-associated infections through progressing in operating standards, minimizing the possibility of contamination during surgery, reducing the establishment of infection by perioperative antibiotic prophylaxis, and confining of pathogenic strains by patient isolation. In spite of these preventions, the percentage of postoperative infections is still rising. Composite coatings with bone-bioactivity and drug-eluting capacity are considered as promising materials for titanium bone implants. In this work, novel drug-eluting chitosan-based coatings are introduced to prevent implant-associated infections. The coatings are fabricated by a single-step electrophoretic deposition technique. The vancomycin antibiotic is co-deposited with the polymer on the surface of Ti implants. Results of Fourier transform infrared spectroscopy and differential scanning calorimetry show hydrogen bonding between the drug and chitosan macromolecules. Therefore, it is suggested that the antibiotic drug is physically incorporated in the chitosan hydrogel coating. Experimental results determines that the maximum amount of drug loading in chitosan and chitosan-bioglass, chitosan-laponite and chitosan-graphene oxide composite coatings were 228, 630, 1090 and 980 µg/cm2, respectively. In vitro evaluation of drug releasing kinetics determines that incorporation of bioglass, laponite and graphene oxide has a significant effect on degradation and drug release behavior of the coatings. Diffusion-controlled mechanism is suggested for the release of the drug from chitosan coatings containing graphene oxide and laponite. The drug release from chitosan and chitosan-bioactive glass coatings is controlled by water uptake and diffusion of the drug macromolecules throughout in accompany with surface erosion (degradation/de-attachment) of the coatings. To tailor the drug releasing rate, a chemically-graded multilayer is introduced. These composite releases the antibiotic with a zero-order mechanism over 4 weeks that is very promising in preventing bacterial infections. Antibacterial tests against Gram-positive Staphylococcus aureus reveal that the infection risk of titanium foils is significantly reduced due to the antibiotic release. Almost no bacteria are survived on the coatings prepared from the electrophoretic suspension containing ≥0.5 g/l vancomycin. The in vitro biological tests indicate that the composite coatings are biocompatible and support cell attachment and proliferation in a MG-63 osteoblast like cell line. No adverse effects of vancomycin on cellular responses are seen. However, a slight reduction in the osteogenesis activity of chitosan coatings containing graphene is detectable. The developed chitosan-based composite coatings with bone bioactivity and long-term drug-delivery ability may be potentially useful for metallic implants to reduced infection risk
  9. Keywords:
  10. Chitosan ; Bioactive Glass ; Graphene Oxide ; Leponite ; Electrophoretic Deposition ; Drug Release

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