A resveratrol/Fe³⁺-doped ZIF-8-augmented dressing for multimodal diabetic wound care

Bacteria-infected diabetic wounds are difficult to heal because the wound microenvironment changes dynamically during different stages of repair, whereas most current treatments provide only static functions. Here, we developed an injectable polysaccharide dressing, AOR1, composed of amino hyaluronic acid, oxidized hyaluronic acid, and resveratrol-loaded Fe³⁺-doped ZIF-8 (RF@ZIF-8), for staged diabetic wound treatment. Unlike many reported nanoparticle-loaded injectable hydrogels with relatively static therapeutic functions, AOR1 provides a pathology-adaptive staged strategy that combines early acidic microenvironment-triggered antibacterial action with subsequent antioxidant, anti-inflammatory, and pro-angiogenic regulation for integrated diabetic wound repair. In acidic infected niches, imine crosslinks trigger RF@ZIF-8 release to generate bactericidal radicals, achieving 99.8% inhibition of Staphylococcus aureus and 99.9% inhibition of Escherichia coli without antibiotics. As infection resolves, resveratrol reestablishes redox homeostasis, attenuates inflammation, and restores pro-angiogenic signaling. In infected diabetic rats, AOR1 reduced residual wound area to 14.3% by day 14. These results indicate that AOR1 provides a pathology-adaptive strategy that integrates early infection control with subsequent microenvironment regulation to promote diabetic wound healing.