Effective management of full-thickness wounds faces significant challenges due to poor angiogenesis and impaired healing. Biomimetic tissue-engineered scaffolds with angiogenic properties can, however, enhance the regeneration capacity of the damaged skin. Here, we developed a hybrid double-layer nanofibrous scaffold, comprised of egg white (EW) and polyvinyl alcohol (PVA), loaded with niosomal Deferoxamine (NDFO) for enhanced angiogenesis and wound healing features. The hybrid scaffold showed enhanced mechanical properties with comparable modulus and shape-recovery behavior of the human skin. Thanks to the porous morphology and uniform distribution of NDFO within the nanofibers, in vitro drug release studies indicated controlled and sustained release of DFO for up to 9 days. The constructs also promoted a significant increase in vascular sprouting area in vitro and enhanced vascular branches ex vivo. In vivo, implantation of the hybrid scaffold in full-thickness wounds in rats revealed early angiogenic response, a higher number of neo-formed vessels, a faster healing rate and complete epithelialization as early as day 10, compared to the control groups. Thus, the presented biomimetic hybrid scaffold with DFO control release features holds great promise in accelerated full-thickness wound healing and soft tissue regeneration