Metal-polyphenol nanocomposite hybrid hydrogel: A multifunctional platform for treating diabetic foot ulcers through...

Diabetic foot ulcer (DFU) is a prevalent and challenging clinical condition characterized by impaired microcirculation, chronic wound infections, and a hyperglycemic, high-reactive oxygen species (ROS) environment. These factors make treatment particularly complex, often requiring a multidisciplinary approach that yields suboptimal results. In this study, a novel therapeutic strategy was developed using metal-polyphenol nanoparticles synthesized from (-)-Epigallocatechin-3-gallate (EGCG) and ferric ions (Fe³⁺). These nanoparticles were further loaded with salvianolic acid B (SAB) and glucose oxidase (GOx) to enhance their multifunctional biological properties. Complementing these nanoparticles, a polysaccharide hydrogel was engineered using quaternized chitosan (QCS) and oxidized fucoidan (OFu), forming a robust and stable network through Schiff base linkages. This innovative platform demonstrated strong antibacterial activity against DFU-associated pathogens. Within the ulcer's hostile microenvironment, the hydrogel degraded via dynamic bond cleavage, releasing nanoparticles that boosted mitochondrial metabolism, induced M2 macrophage polarization, promoted angiogenesis and reduced ROS levels. These combined effects accelerated tissue regeneration and wound healing. The results suggest that this advanced hydrogel system holds significant promise as a therapeutic option for improving DFU management and addressing its multifaceted challenges.