AbstractThe present study aims to fabricate cellulose nanocrystals (CNCs) doped poly(vinyl alcohol) polyethylene glycol (PVA/PEG) nanocomposite films for biomedical applications. The nanocomposite films were prepared by using electrospinning techniques with varying percentages of CNCs (10% and 20%) mixed with PVA and PEG (50:50). The properties of the produced nanocomposites were evaluated using a battery of tests. The results of surface morphology and structural miscibility obtained from field emission‐scanning electron microscopy (FE‐SEM), atomic force microscopy, and Fourier transformer infra‐red studies revealed appreciable compatibility among the three components (CNCs, PVA, and PEG). FE‐SEM micrographs revealed that the nanomaterials underwent a dramatic transition from discontinuous to continuous fibers, with interconnected or network‐like fibers. The constructed scaffold material's stability went up from three to four phases, according to thermal and degradation experiments. In addition, research on biodegradation and water absorption found that CNCs outperformed pure PVA and PVA/PEG in terms of swelling percentage time and enzyme degradation rate. The hemolysis assay of the PVA/PEG/CNC scaffold showed good compatibility (below 5%) and according to the MTT assay, both NIH 3T3 and L929 cells survived well, indicating that the CNCs could serve as a useful scaffold for tissue engineering applications such skin tissue regeneration. In sum, the findings proved that biological domains including tissue engineering and wound healing can benefit from produced nanofiber scaffolds.