Background:Safe and effective wound healing can be a major clinical challenge. Inflammation and vascular impairment are two main causes of inadequate wound healing.Methods:Here, we developed a versatile hydrogel wound dressing, comprising a straightforward physical mixture of royal jelly-derived extracellular vesicles (RJ-EVs) and methacrylic anhydride modified sericin (SerMA), to accelerate wound healing by inhibiting inflammation and promoting vascular reparation.Results:The RJ-EVs showed satisfactory anti-inflammatory and antioxidant effects, and significantly promoted L929 cell proliferation and migrationin vitro. Meanwhile, the photocrosslinked SerMA hydrogel with its porous interior structure and high fluidity made it a good candidate for wound dressing. The RJ-EVs can be gradually released from the SerMA hydrogel at the wound site, ensuring the restorative effect of RJ-EVs. In a full-thickness skin defect model, the SerMA/RJ-EVs hydrogel dressing accelerated wound healing with a healing rate of 96.8% by improving cell proliferation and angiogenesis. The RNA sequencing results further revealed that the SerMA/RJ-EVs hydrogel dressing was involved in inflammatory damage repair-related pathways including recombinational repair, epidermis development, and Wnt signaling.Conclusion:This SerMA/RJ-EVs hydrogel dressing offers a simple, safe and robust strategy for modulating inflammation and vascular impairment for accelerated wound healing.