Photochemically fabricated peptide hydrogels from de novo design to application in antibacterial therapy and wound healing

Abstract De novo designed peptide amphiphiles have been exemplified as building blocks for direct fabrication of biofunctional hydrogels through a photochemical approach. Herein, by incorporating diphenylalanine (FF) as a self-assembling antibacterial motif and dityrosine (YY) as a photocrosslinkable unit, the peptide sequences are interconnected through alternating hydrophilic D (L-aspartate) and hydrophobic X (ε-aminocaproic acid) residues to achieve a precise balance between non-covalent fibrillization and covalent crosslinking. Upon visible-light irradiation, these peptides undergo rapid photocrosslinking in aqueous media, yielding hydrogels with tunable gelation properties, robust mechanical stability, and adjustable functionality. The optimized 4Y6F hydrogel exhibits strong antibacterial efficacy against both Gram-positive and Gram-negative bacteria, attributed to synergistic structural interactions. In vivo wound healing studies demonstrate accelerated re-epithelialization, enhanced collagen deposition, and improved angiogenesis, significantly outperforming control groups and commercial formulations. This study presents a versatile peptide platform for the photochemical fabrication of hydrogels, advancing from de novo design to practical applications in antibacterial therapy and wound healing, and offering a promising bottom-up approach for a wide range of biomedical scenarios.