Skin engineering offers innovative constructs for the treatment of a wide range of skin diseases. Hybrid scaffolds were fabricated using poly (vinyl alcohol), gelatin and ZnO nanoparticles by electrospinning. Different concentrations of ZnO nanoparticles (0%, 0.5% and 1%) were incorporated into the PVA/gelatin scaffolds and the constructs were characterized by SEM, FTIR, XRD, contact angle, swelling, degradation, and biomechanical tests; the release behavior of nanoparticles from the scaffolds was also evaluated. In cellular studies, human mesenchymal stem cells (hu-MSCs) were extracted from the umbilical cord of a newborn baby and characterized by flow cytometry. Cell-seeded scaffolds were assessed by in vitro biocompatibility, SEM images and live/dead assay. Finally, the antibacterial activity of scaffolds against E. coli and S. aureus strain was determined. Due to the presence of the hydrophilic biopolymer of gelatin in the contact angle test, the scaffolds showed hydrophilic properties. With the addition of nanoparticles, the hydrophilicity, water absorption and degradation rates of scaffolds were somewhat reduced. No difference in tensile modulus was observed between scaffolds. The release rate of nanoparticles from scaffolds increased over time. The immunoprofile evaluation of extracted cells by flow cytometry technique confirmed the mesenchymal nature of the cells. Fluorescent staining showed that most cells were alive and had appropriate shape during six days of cell culture on PVA/gelatin/ZnO1wt% scaffold. All scaffolds had acceptable biocompatibility, but control and PVA/gelatin groups showed a higher cell survival rate. Scaffolds containing nanoparticles had a direct effect on inhibiting bacterial growth in a dose-dependent manner. Our findings suggest that composite scaffolds containing ZnO nanoparticles seeded with hu-MSCs might be suitable for promoting skin healing.