Dual-functional antimicrobial coating based on a quaternary ammonium salt from rosin acid with in vitro and in vivo antimicrobial and antifouling properties

摘要

Bacterial colonization and biofilm formation on indwelling medical devices potentially cause serious and life-threatening infections. Technologies to prevent bacterial colonization and biofilm formation on biomedical devices are in great demand. Here, we report the preparation of coating monomers by conjugating rosin acid-derived maleopimaric acid quaternary ammonium cation (MPA-N+) with different chain of lengths allyloxy polyethylene glycol (APEG; either MW 1200 or 2400). The monomers of the cation plus its linker conjugates (APEG(1200/2400)-MPA-N+) were further grafted onto the surface of silicone rubber slides (PDMS) via plasma/UV-induced surface polymerization to form antimicrobial and antifouling coatings. The dual-functional coatings exhibited excellent antimicrobial activities against gram-negative and positive bacteria, and they effectively prevented biofilm formation. The coatings also greatly reduced protein adsorption and platelet adhesion, indicating their excellent antifouling capability. In addition, the APEG(1200/2400)-MPA-N+ cation coatings were biocompatible towards mammalian cells, as shown by in vitro cytotoxicity assays using rabbit erythrocytes and attached human aorta smooth muscle cells. In addition, the APEG(2400)-MPA-N+ coating exhibited significant anti-infective activity in a rodent subcutaneous infection model. We show that the APEG(2400)-MPA-N+ coating is an effective strategy for the prevention of infections associated with indwelling biomedical devices.