The electrospun nanofibers and porous scaffolds hold great promise in regenerative medicine. A novel nanofiber- hydrogel‑silicone tri-layer wound dressing has been designed and fabricated to address the limitations of each platform. The bottom nanofiber layer with a 110 mm diameter meets the wound surface and regulates cell attachment and migration. The middle hydrogel layer was fabricated through the optimization of chemical crosslink formation and freezing-thawing cycles (physical crosslink). The fabricated hydrogel with inter- connected porous structure has optimized properties (gel fraction (89.45 %) and porosity (80 %)) for wound dressing application. The silicone layer on the outer surface was designed to fix the wound dressing on the skin and prevent the penetration of pathogens. The scanning electron microscope micrograph showed structural integrity in the tri-layer scaffold. In vivo data showed that the tri-layer scaffold accelerates wound healing in the mice model and angiogenesis in the chorioallantoic membrane model. Therefore, the designed scaffold inspired by the skin\\\\\\\'s structure can be used as a wound dressing to treat woun

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