Novel antimicrobial biomaterials based on cationic peptides

Abstract

It is envisaged that in our technologically advanced society, every person would have a biomedical device or implant in their life time. However, bacterial infections on these life-saving devices have emerged as a major problem. Consequently, there is an urgent need to develop biomaterial surfaces which resist bacterial adhesion and colonisation. Melimine is a synthetic cationic peptide with excellent broad-spectrum antimicrobial activity. Further, this peptide is not cytotoxic at active concentrations and is readily heat-sterilizable. In this study, we explored the ability of Melimine to prevent bacterial adhesion when covalently tethered on glass and FEP using two attachment strategies: non-specific attachment via azide linkers and site-directed attachment via maleimide linker. The melimine coated surfaces showed excellent activity against P. aeruginosa and S. aureus with up to 40-fold reduction in bacterial adhesion compared to the untreated samples in vitro. The influence of tethering parameters were also examined, peptide concentration, orientation and linker reactivity were found to be important factors to consider for optimal activity. In vivo efficacy of melimine was also demonstrated with a 1-log reduction in viable bacteria compared with the controls in a subcutaneous mouse model. Solution-based antibacterial assays were also carried out for palmitoylated melimine and melimine-coated beads. Melimine has demonstrated excellent potential for further development as an effective antimicrobial coating in the prevention of device-related infections.