This study explores the fabrication of tannic acid-crosslinked gelatin nanofibers via electrospinning, followed by helium and nitrogen plasma treatment to enhance their biofunctionality, which was assessed using fibroblast cells. The nanofibers were characterized using scanning electron microscopy, atomic force microscopy, attenuated total reflection Fourier transform infrared spectroscopy, X-ray diffraction, and water contact angle measurements before and after treatment. Helium and nitrogen gas plasma were employed to modify the nanofiber surfaces. Results indicated that helium and nitrogen plasma treatment significantly increased the hydrophilicity and biofunctionality of the nanofibers by 5.1° ± 0.6 and 15.6° ± 2.2, respectively, making them more suitable for human skin fibroblast applications. To investigate the impact of plasma treatment on gelatin, we employed a computational model using density functional theory with the B3LYP/6-31+G(d) method. This model represented gelatin as an amino acid chain composed of glycine, hydroxyproline, and proline, interacting with plasma particles. Vibrational analysis of these systems was used to interpret the vibrational spectra of untreated and plasma-treated gelatin. To further correlate with experimental findings, molecular dynamics simulations were performed on a system of three interacting gelatin chains. These simulations explored changes in amino acid bonding. The computational results align with experimental observations. Comprehensive analyses confirmed that these treatments improved hydrophilicity and biofunctionality, supporting the use of plasma-treated gelatin nanofibers in skin tissue engineering applications. Gelatin’s natural biopolymer properties and the versatility of plasma surface modification techniques underscore its potential in regenerating cartilage, skin, circulatory tissues, and hamstrings.
