Journal
MATERIALS SCIENCE AND ENGINEERING C-MATERIALS FOR BIOLOGICAL APPLICATIONS
Volume 116, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.msec.2020.111109
Keywords
Bio-orthogonal chemistry; Antimicrobial titanium coating; Prodrug antibiotic; Antibiotic delivery; Antibiotic release
Categories
Funding
- National Science Foundation of the United States [1664577]
- National Institutes of Health, United States of America [1R21CA228997-01]
- Direct For Mathematical & Physical Scien
- Division Of Chemistry [1664577] Funding Source: National Science Foundation
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Implant-associated infections present severe and difficult-to-treat complications after surgery, related to implant biofilm colonization. Systemic administration of antibiotics cannot reach sufficient concentrations at the infected site and may be toxic. Here we describe how mussel-inspired dendritic material coated on a titanium surface can locally activate a prodrug of daptomycin (pro-dapto) to treat methicillin-resistant Staphylococcus aureus. The mechanism of the prodrug activation is based on bio-orthogonal click chemistry between a tetrazine (Tz) and trans-cyclooctene (TCO). The former is attached to the dendritic polymer, while the later converts daptomycin into a prodrug. Characterization of the material's properties revealed that it is hydrophobic, non-toxic, and stable for a prolonged period of time. We envision that the titanium coated dendritic material will be able to improve the treatment of implant-associated infections by concentrating systemically administered antibiotic prodrugs, thus converting them into active localized medicines.
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