Photo-crosslinkable hydrogel with programmable dual time-phase drug release for accelerated healing of infected diabetic wounds

Chronic diabetic wounds remain a critical unmet challenge in clinical care, largely due to persistent bacterial infections and unresolved inflammation, leading to impaired healing. While photo-crosslinkable hydrogels offer localized therapeutic delivery, existing systems often face limitations in ease of modification and comprehensive multi-functional efficacy. Herein, we present a light-activated hydrogel dressing featuring programmable, dual time-phase drug release and simplified modification of crosslinking matrices to address these barriers in a synergistic manner. This intelligent system integrates a ciprofloxacin-caged photo-crosslinker (PCA-CIP), hyaluronic acid (HA), and metformin-loaded poly(lactic-co-glycolic acid) nanoparticles (MET@NPs). Upon brief photo-irradiation, the hydrogel rapidly crosslinks (<52 s), releasing ciprofloxacin immediately at the wound site for rapid anti-bacterial action. Concurrently, MET@NPs enable sustained delivery of metformin to modulate inflammation over an extended period. This spatiotemporally coordinated release, characterized by an initial burst of antibiotics followed by prolonged anti-inflammatory activity, fosters a favorable microenvironment for tissue regeneration. In both in vitro and full-thickness diabetic wound models, the hydrogel exhibits strong tissue adhesion, potent infection control, durable immunomodulation, and significantly enhanced healing. This work demonstrates the clinical promise of dual time-phase hydrogels as precision-engineered wound therapies for diabetes-related complications.