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Bioactive Nanocomposite Coatings Containing Anti-Bacterial Factors with Controlled Release on the Bone Implant

Zarghami, Vahid | 2020

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  1. Type of Document: Ph.D. Dissertation
  2. Language: Farsi
  3. Document No: 52807 (48)
  4. University: Sharif University of Technology
  5. Department: Institute for Nanoscience and Nanotechnology
  6. Advisor(s): Ghorbani, Mohammad; Shokrgozar, Mohammad Ali; Pooshang Bagheri, Kamran
  7. Abstract:
  8. Aseptic loosening and infection are two major problems of bone implants. Aseptic loosening occurs due to poor cell growth and poor adhesion to the implant surface over time. Bone infection at the implant site occurs mainly by the staphylococcus aureus bacteria. In some cases, infection occurs in the short term and in the early times after implantation, and in some cases, infection occurs in later times. The aim of this study is to synthesize and evaluate antibacterial coatings, while having cell growth-promoting components and cell differentiation to solve bone implant problems simultaneously. Also, the issue of bacterial resistance to antibiotics and their risks in bone implants is another area of interest in this study. In the first step, in order to have long-term antimicrobial activity, vancomycin was immobilized on bioactive glass nanoparticles. The results of FT-IR, TGA, zeta potential measurement and DLS confirmed the successful immobilization of vancomycin on the nanoparticles. The amount of bounded drug to the nanoparticles was about 64 micrograms per mg of the nanoparticles. Drug release was studied by UV-Vis technique. In the early times, drug release was about 20% for modified nanoparticles with attached vancomycin, whereas in the absence of binding drug to nanoparticles, the initial release was 45%. Also, after 28 days the release of the drug reached about 65% for modified nanoparticles with attached drug. The minimum bactericidal concentration (MBC) of nanoparticles for methicillin-resistant Staphylococcus aureus bacteria (MRSA) obtained 1.25 mg / ml. In order to have long-term anti-infectious multifunctional composite coatings, chitosan- vancomycin-linked to bioactive glass nanoparticles and chitosan-bioactive glass-vancomycin nanocomposite coatings were synthesized and their biological properties were compared. In this study, the antibacterial capability of coatings against MRSA bacteria was evaluated for two weeks. The results showed that after two weeks in the coatings with attached drug, the amount of bacteria present in the above bacteria solution of the samples and the adherent bacteria to the surface of samples were 4 and 2 logarithmically lower than the chitosan-vancomycin-glass nanoparticle coating, respectively. There is a delay in ALP secretion and differentiation of MC3T3 cells of chitosan-bioactive glass-vancomycin coating, which it disappears due to the control of explosive release of vancomycin in coatings with immobilized vancomycin. It indicates the positive effect of drug binding to the surface of nanoparticles on bone formation. In the second step, antimicrobial peptide, Melittin was used to counteract antibiotic resistant bacteria in bone implant infections and prevent biofilm formation on them. For this purpose, two types coatings include chitosan- bioactive glass nanoparticles- tetracycline- melitine and chitosan- bioactive glass nanoparticles- vancomycin- Melittin were synthesized. The presence of Melittin in the coatings improved cell growth but had no positive effect on cell differentiation and secretion of alkaline phosphatase. The presence of tetracycline in the coatings, in addition to its antibacterial activity, induced the secretion of the alkaline phosphatase enzyme and promoted cellular differentiation, allowing it to be versatile in the coating. Since vancomycin-resistant bacteria (VRSA) are spreading, the synergy of Melittin and vancomycin completely eliminates these bacteria and it is a response to human concern about bacterial resistance to vancomycin
  9. Keywords:
  10. Chitosan ; Tetracyclines ; Vancomycin Antibiotic ; Bioactive Glass ; Chemical Immobilization ; Antimicrobial Peptide Melittin ; Multifunctional Coatings ; Antibiotic Resistant Bacteria ; Bone Implant ; Loosening

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