Antimicrobial peptide modification of biomaterials using supramolecular additives

Biomaterials based on non-active polymers functionalized with antimicrobial agents by covalent modification or mixing are currently regarded as high potential solutions to prevent biomaterial associated infections that are major causes of biomedical device failure. Herewith a strategy is proposed in which antimicrobial materials are prepared by simply mixing-and-matching of ureido-pyrimidinone (UPy) based supramolecular polymers with antimicrobial peptides (AMPs) modified with the same UPy-moiety. The N-terminus of the AMPs was coupled in solution to an UPy-carboxylic acid synthon resulting in formation of a new amidic bond. The UPy-functionalization of the AMPs did not affect their secondary structure, as proved by circular dichroism spectroscopy. The antimicrobial activity of the UPy-AMPs in solution was also retained. In addition, the incorporation of UPy-AMPs into an UPy-polymer was stable and the final material was biocompatible. The addition of 4 mol % of UPy-AMPs in the UPy-polymer material protected against colonization by Escherichia coli, and methicillin-sensitive and -resistant strains of Staphylococcus aureus. This modular approach enables a stable but dynamic incorporation of the antimicrobial agents, allowing at the same time for the possibility to change the nature of the polymer, as well as the use of AMPs with different activity spectra.