Antimicrobial ceragenins inhibit biofilms and affect mammalian cell viability and migration in vitro

The healing of burn wounds is often hampered by bacterial infection and the formation of biofilms. Antimicrobial peptides (AMPs) are effective in promoting wound healing, but are susceptible to degradation. We have tested the ability of ceragenins (CSAs), mimics of antimicrobial peptides, to mitigate preformed biofilms and stimulate wound healing in vitro. Potent CSAs (MICs < 10 μg·mL^-1) were tested against biofilms formed from a mixture of Pseudomonas aeruginosa and Staphylococcus aureus grown for 22 h and subjected to 20 h treatment. Many CSAs showed more potent anti-biofilm activity than the endogenous AMP LL-37, and CSA-13 and CSA-90 decreased the amount of biofilm matrix substances detected by SYPRO Ruby stain. Effects on mammalian cells were measured by viability, migration, and tube formation assays in vitro. Although CSAs were toxic to immortalized human keratinocytes (HaCaTs) at higher concentrations (>10 μg·mL^-1), lower concentrations of CSA-13 and CSA-192 stimulated cell migration. CSA-13, CSA-90, and CSA-142 also stimulated tube formation in an in vitro angiogenesis model. An inhibitor of vascular endothelial growth factor receptor 2 (VEGFR2) blocked tube formation stimulated by CSA-13, suggesting that CSA-13 signals through this receptor. Ceragenins display anti-biofilm activity and stimulate migration and tube formation in vitro. This work suggests that ceragenins have the potential to be both topical antimicrobials and wound-healing adjunct therapeutics.