A multi-physically cross-linked roxadustat-loaded hydrogel for promoting diabetic wound healing via antibacterial, antioxidant and angiogenesis acceleration functions

Abstract

Wound healing poses a significant clinical challenge, especially for diabetic wounds, and patients face limitations such as delayed healing, increased risk of infection, and poor outcomes. Traditional wound care strategies often fail to address these issues effectively. In this study, we introduce a novel multivalent cross-linked hydrogel (CS/PVA/TA@FG) composed of chitosan (CS), polyvinyl alcohol (PVA), tannic acid (TA), and the hypoxia-inducible factor prolyl hydroxylase inhibitor FG4592 (FG) for enhanced diabetic wound healing. Highly elastic hydrogels can create an optimal wound healing environment by providing moisture, reducing oxidative stress, modulating inflammation, and preventing bacterial infection. The porous CS/PVA/TA@FG hydrogel exhibited high moisture retention, toughness, and stability and excellent biocompatibility. In vitro studies demonstrated the ability of the CS/PVA/TA@FG hydrogel to promote angiogenesis, cell proliferation, and migration, which are essential for effective wound healing. In vivo experiments in a diabetic mouse model revealed accelerated wound closure, increased blood perfusion, and enhanced tissue regeneration with the application of the CS/PVA/TA@FG hydrogel. Our study presents a promising therapeutic strategy for diabetic wound care, offering a holistic approach to enhancing wound healing by addressing the key challenges of oxidative stress, inflammation, and impaired angiogenesis.