A dual-network photocrosslinking antibacterial hydrogel with ROS-responsive release of tannic acid–cerium complex for restoring metabolic homeostasis in diabetic wound healing

Excessive ROS create a chronic inflammatory microenvironment in diabetic wounds, while hyperglycemia promotes bacterial infection, together driving a vicious cycle of tissue damage. In this study, a cerium–tannic acid coordinated metal–polyphenolic network (Ce@PTA MPN) was developed to scavenge ROS at the wound site. This complex was subsequently integrated into a phenylboronic acid-modified methacrylated hyaluronic acid–PEG hybrid hydrogel, designed as a functional wound dressing. The Ce@PTA MPN exhibited efficient ROS-scavenging ability via catalytic activity. Additionally, the photo-crosslinked hybrid hydrogel demonstrated favorable mechanical properties, including tensile strength and self-healing capability. Notably, the Ce@PTA complex was released in response to oxidative stimuli due to the reversible phenylboronic ester linkage between tannic acid and the modified hydrogel (b-Gel), which enhanced antioxidant, antibacterial and anti-inflammatory efficacies while minimizing potential cytotoxicity. In animal experiments, Ce@PTA b-Gel accelerated skin defect repair by inhibiting bacterial proliferation and promoting epidermal regeneration. The expression of pro-inflammatory cytokines was reduced, while CD31 expression was increased in the regenerated skin. Transcriptomic analysis revealed that the therapeutic mechanism of Ce@PTA b-Gel involved the dual suppression of inflammatory signaling and restoration of metabolic homeostasis. Collectively, Ce@PTA b-Gel may represent a potential therapeutic strategy for the treatment of diabetic wounds.