期刊
MATERIALS SCIENCE & ENGINEERING C-MATERIALS FOR BIOLOGICAL APPLICATIONS
卷 90, 期 -, 页码 289-299出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.msec.2018.04.068
关键词
Ag-doped TiCaPCON films; Antibiotic-loaded surface; Bactericide release; Antibacterial activity; Pathogenic bacteria; Fungi
资金
- Ministry of Education and Science of the Russian Federation [K2-2016-011]
Implant-related bacterial infections remain a serious problem that is not solved yet. Herein we combined several antibacterial agents to achieve synergistic effects and broader protection of widely used metallic implants. Titanium samples with microcontainers for drug, produced by selective laser sintering, were coated with Ag-doped biocompatible and bioactive TiCaPCON film and loaded with an antibiotic (gentamicin or a mixture of gentamicin and amphotericin B). Bactericide release tests demonstrated that the release rate of one bactericide agent (Ag+ ions or gentamicin) depended on the presence of the other antibacterial component. The antibacterial activity of the biocide-doped samples was evaluated against clinically isolated Escherlchia colt 078 (E. colt), Staphylococcus aureus (S. aureus) bacteria, and Neurospora crassa wt-987 (N. crassa) spores. It was found that samples loaded with low gentamicin concentration (0.2 and 0.02 mg/cm(2)), i.e. 10 and 100 times less than the standard gentamicin concentration (2 mg/cm(2)), demonstrated a superb antibacterial activity against E. colt bacteria. We showed that a crosslinking reaction between gentamicin and TiCaPCON film proceeded either through the formation of amide bonds or via the electrostatic interaction between amine groups of gentamicin and COOH groups of TiCaPCON and led to the formation of relatively stable drug/film conjugates that prevented a rapid dissolution of gentamicin and ensured its long-term (for 72 h) antibacterial protection. Leaching of silver ions provided an effective antibacterial protection after the depletion of the drug reservoirs. The obtained results clearly show a synergistic antibacterial action of Ag+ ions and gentamicin against S. aureus bacteria. In addition, in the presence of Ag+ ions, the antifungal activity of samples loaded with a mixture of gentamicin and amphotericin B against N. crassa fungus was observed to increase. Thus, it is demonstrated that silver can be successfully coupled with different types of antibiotics to provide innovative hybrid metal-ceramic bio-constructions that are able to deliver precise doses of bactericide agents within a certain period of time and are equally effective against Gram-negative E. colt bacteria, Gram-positive S. aureus, and N. crassa fungus.
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