Antimicrobial Peptide SAAP-148-Functionalized Hydrogels from Photocrosslinkable Polymers with Broad Antibacterial Activity.

Abstract

Antimicrobial peptides (AMPs) are promising alternatives to traditional antibiotics for treating skin wound infections. Nonetheless, their short half-life in biological environments restricts clinical applicability. Covalent immobilization of AMPs onto suitable substrates offers a comprehensive solution, creating contact-killing surfaces with long-term functionality. Here, a copolymer of poly[(hydroxy ethyl acrylamide)-co-(4-benzophenone acrylamide)-co-(pentafluorophenyl acrylate)-co-(ECOSURF EH-3 acrylate)], in short poly(HEAAm-co-BPAAm-co-PFPA-co-EH3A), is synthesized by free radical polymerization. Subsequent modification of active ester groups with the amine groups of SAAP-148, results in a copolymer, that is non-cytotoxic to human lung fibroblasts. UV photocrosslinking of the benzophenone units yields a polymer network that forms a hydrogel after swelling with aqueous medium. Both the SAAP-148-modified polymer in solution and the photocrosslinked hydrogels show good antimicrobial activity against strains of Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Acinetobacter baumannii, including multidrug-resistant strains, frequently found in wound infections. The covalent attachment of SAAP-148 prevents leaching, ensuring sustained antimicrobial activity for at least 48 h in diluted human blood plasma and 14 days in PBS. This prolonged retention of antimicrobial activity in human blood plasma significantly enhances its clinical potential. Overall, this study shows the potential of the AMP-functionalized photocrosslinkable polymer as antimicrobial wound dressings, providing an effective alternative to antibiotics.