Regenerative potential of biogenic zinc oxide nanoparticles prepared with Vitis vinifera-derived extract on sciatic nerve injury in rats

<i>Objective.</i>Damage to the peripheral nerves frequently leads to significant impairments in their functional capacity, highlighting the need for effective treatments that can facilitate nerve repair. This study explores the potential of grape skin extract (Ex), alone and in combination with zinc oxide nanoparticles (ZnO NPs), to enhance regeneration following sciatic nerve injury (SNI) in rats.<i>Approach.</i>ZnO NPs were synthesized using both a conventional chemical route and a green synthesis method in which Ex served as a natural reducing and capping agent. The synthesized nanoparticles were characterized by Fourier-transform infrared spectroscopy, scanning electron microscopy, x-ray diffraction, Thermogravimetric analysis, Energy-dispersive x-ray spectroscopy, zeta potential, and Gas chromatography-mass spectrometry analyses to confirm the role of Ex in shaping nanoparticle morphology and surface properties. Functional recovery and histological outcomes were then assessed in a murine SNI model.<i>Main results.</i>Treatment with Ex and ZnO/Ex significantly reduced collagen accumulation, fibrosis, and tissue vacuolization compared to untreated controls. Both interventions also improved myelination and enhanced the sciatic function index, indicating improved neural repair.<i>Significance.</i>These findings demonstrate that Ex and ZnO/Ex promote nerve regeneration and highlight their potential as promising candidates for the development of biogenic nanotherapeutics targeting peripheral nerve injuries.