531. Titanium coating with mussel inspired polymer and bio-orthogonal chemistry enhances antimicrobial activity against Staphylococcus aureus
M. Czuban, M. W. Kulka, L. Wang, A. Koliszak, K. Achazi, C. Schlaich, I. S. Donskyi, M. Di Luca, J. M. Mejia Oneto, M. Royzen, R. Haag – 2020
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.