Biological macromolecules, such as polysaccharides and proteins, are considered ideal options for use in skin tissue engineering, both in vitro and in vivo, due to their suitable biocompatibility and biodegradability. Despite numerous studies that have been conducted in this area, there is a need to construct a scaffold with antibacterial properties and desirable biocompatibility. The aim of this study is to construct and evaluate a core-shell electrospun scaffold for skin tissue engineering. In this structure, polyurethane acts as the shell, and a mixture of starch, propolis extract, and hyaluronic acid forms the core. The morphology of the scaffold was determined using scanning electron microscopy and transmission electron microscopy. The physical and mechanical properties of the scaffold, including contact angle, Young's modulus, and strain at break, were evaluated. The antibacterial activity of the scaffold against Staphylococcus aureus and Escherichia coli was investigated. The cytotoxicity of the scaffold was evaluated using L929 fibroblast cells. The effectiveness of the scaffold in wound healing under in vivo conditions was also investigated. Microscopic images showed that the core-shell structure was successfully formed. The contact angle of the scaffold was 56.7 degrees, indicating suitable hydrophilic properties for cell attachment. Mechanical tests showed a Young's modulus of 8.12 MPa and a strain at break of 46%, indicating an optimal balance between mechanical strength and flexibility. The scaffold exhibited strong antimicrobial activity against Staphylococcus aureus and Escherichia coli. Cytotoxicity evaluations showed no toxicity, and the adhesion and proliferation of L929 fibroblast cells on the scaffold were increased. Studies conducted under in vivo conditions confirmed the potential of the scaffold in tissue engineering and showed wound healing. The results of this study show that the electrospun scaffold with a polyurethane shell and a starch/propolis extract/hyaluronic acid core is a versatile and promising platform for advanced applications in skin tissue engineering and regenerative medicine.