Biochemical strategy-based hybrid hydrogel dressing-mediated in situ synthesis of selenoproteins for DFU immunity-microbiota homeostasis regulation

Chronic consequences of diabetes that are most commonly encountered are diabetic foot ulcers (DFUs), driven by microbiota-immune system dyshomeostasis, eventually leading to delayed wound healing. Available therapies, such as systemic or topical administration of anti-inflammatory or antimicrobial agents, are limited due to antibiotic resistance and immune dysfunction. Herein, a hybrid hydrogel dressing is developed as the artificial bioadhesive barrier at wound sites to maintain microbial and immunological homeostasis locally and have potent anti-inflammatory effects. Specifically, Zero-valent selenium nanoparticles are synthesized and encapsulated into the alginate-polyacrylamide interpenetrating hydrogel networks, during which trehalose is adopted to modify the network defects. Besides, as an anti-adhesion agent, trehalose has shown the ability to prevent immune degradation by reducing bacteria binding to HUVECs. The obtained hybrid hydrogel dressing serves as a physical barrier against microbiome invasion, further regulates the composition of the wound microbiome to restore microbial immune homeostasis at the wound site, and cooperatively relieves DFU-associated symptoms. Meanwhile, the hydrogel dressing can synthesize selenoproteins in situ based on biochemical strategies and significantly reduce the secretion of proinflammatory cytokines. The proposed biochemical strategy based on the hybrid hydrogel dressings can efficiently restore microbiota-immune homeostasis in the wounds, presenting a promising approach for DFU therapy in clinics.