Bioinspired Intrinsic Versatile Hydrogel Fabricated by Amyloidal Toxin Simulant-Based Nanofibrous Assemblies for Accelerated Diabetic Wound Healing

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-NH2, 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 1 alpha (HIF-1 alpha) 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.

Automated summary

This study investigated a versatile hydrogel based on amyloid-derived toxin simulant, which promotes angiogenesis, has broad-spectrum antibacterial activity, and accelerates wound healing for diabetic patients, showing great potential for clinical application.