Abstract

Persistent microbial infection and decreased neovascularization are common issues associated with diabetic wound treatment. Hydrogel dressings that offer intrinsic antibacterial and angiogenesis-inducing may substantially avoid the use of antibiotics or angiogenic agents. Herein, a versatile hydrogel is fabricated using an amyloid-derived toxin simulant (Fmoc-LFKFFK-NH 2 , FLN) as building blocks, inspired by the defense strategy of Staphylococcus aureus (S. aureus) . The simulant assemblies of the hydrogel function as both matrix components and functional elements for diabetic wound treatment. The hydrogel undergoes quick assembly from random monomers to nanofibrils with abundant b -sheet driven by multiple non-covalent interactions. The developed hydrogel demonstrates excellent biocompatibility and accelerates angiogenesis via hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor A (VEGFA) signaling as a consequence of its amyloidal structure. The simulant-based nanofibrils endow the hydrogel with broad-spectrum antibacterial activity dominated by a membrane-disruption mechanism. In addition, the hydrogel exhibits excellent performance compared with the commercial hydrogel Prontosan in accelerating wound healing of diabetic mice infected with methicillin-resistant S. aureus (MRSA). This study highlights the fabrication of a single component and versatile hydrogel platform, thereby avoiding the drug-related side effects and complicated preparations and demonstrating its profound potential as a clinical dressing for the management of microbe-infected diabetic wounds.