Wound healing refers to a complex, dynamic process in the body, especially the skin, which influences the quality of life of millions of people each year. Electrospinning is an efficient and economic technique for the production of micro-to nano-fibrillar constructs as drug delivery systems with biomedical applications. In this study, we designed an electrospun bilayer fibrillar scaffold immobilized with epidermal growth factor (EGF), using polycaprolactone (PCL) as the upper layer and chitosan (CS)/polyvinyl alcohol (PVA) as the lower layer of wound dressing. The scanning electron microscopy (SEM) was utilized to characterize the scaffolds. The water uptake, release potency, and toxicity of scaffolds were evaluated, and also then DAPI staining and MTT assay after seeding adipose tissue-derived mesenchymal stem cells. Finally, the effects of the scaffolds on the wound healing process were investigated in a mouse model of full-thickness skin injury. The results of SEM demonstrated continuous, smooth, bead-free, and randomly aligned fibers. The average diameter of CS/PVA nanofibers was 238.36 ± 36.99, and the mean diameter of PCL nanofibers was 1271.79 ± 428.49 nm. The scaffolds were capable of cell seeding and supported their growth and proliferation. Furthermore, in the comparison between designed composite as dressing patch and control group (Vaseline), our composite demonstrated significant differences, so that EGF-immobilized patch efficiently accelerated wound closure and improved histological healing in an in vivo full-thickness wound healing mouse model. The present results suggest the potential of the designed electrospun bilayer fibrillar scaffold containing EGF for the treatment of fullthickness wounds and skin regeneration. K E Y W O R D S chitosan/polyvinyl alcohol/polycaprolactone, epidermal growth factor (EGF), mesenchymal stem cells, skin regeneration, wound healing 1 | INTRODUCTION Skin is one of the vital body tissues, which is composed of dermis, epidermis, and hypoderm (subcutaneous fat) layers and covers the external body surface. It constitutes almost 8% of the total mass of the body and has several crucial functions. 1 It provides an effective barrier against adverse external conditions and has properties, which can prevent microbial, mechanical, chemical, osmotic, thermal, and photo damage. Skin wounds, which can be caused by burns, venous ulcers, diabetic ulcers, and acute injury, are categorized into several types. Generally, wound healing is a dynamic and complex process, which is able to restore the skin's routine functionality and anatomical