pH-Responsive Peptide-Polymer Hydrogel for Biofilm Disruption

Abstract

Biofilm formation presents a significant challenge in chronic infections as it enables bacteria to resist conventional antibiotics and thrive in various areas of the body. The treatment is further hurdled by the acidic environment of biofilms due to anaerobic glycolysis of bacteria and the accumulation of acidic byproducts. Therefore, there is a need for the development of antimicrobial materials that can selectively and preferentially eradicate biofilms in the acidic environment. Toward this aim, this study explores the use of acid-responsive double-network peptide-polymer hydrogels encapsulated with antimicrobial peptides to effectively target and disrupt biofilms. The hydrogel consists of two essential components: a self-assembling peptide nanofiber containing a non-natural ionic amino acid, which imparts pH responsiveness in the weakly acidic range, and a 4-arm PEG polymer that forms covalent bonds with the peptide nanofiber, enhancing the hydrogel's mechanical strength. Upon acidification, peptide nanofibers disassemble, causing an increased pore size of the hydrogel and release of encapsulated antimicrobials to the biofilm site. We expect that, by leveraging the unique properties of the double network self-assembled peptide-PEG hydrogels and the pH-triggered release mechanism, this innovative hydrogel approach may offer a more targeted, effective, and safer treatment option against biofilm-associated infections.

Keywords: Self-assembly; antibiofilm activity; non-natural amino acids; pH-responsive hydrogel; peptide−polymer conjugates.