Fabrication and <i>in-vitro</i> and <i>in-vivo</i> evaluation of polyacrylonitrile and polyethylene oxide nanofibers loaded with resveratrol and silver nanoparticles for skin wound healing application

This study developed hybrid nanofiber scaffolds composed of polyacrylonitrile (PAN) and polyethylene oxide (PEO), loaded with resveratrol (RSV) and silver nanoparticles (Ag NPs), aiming to enhance wound healing and provide antimicrobial protection. Using electrospinning combined with a full factorial design, we optimized formulation parameters including total polymer concentration, drug/polymer ratio, and PEO/polymer ratio. We found that increasing the drug/polymer ratio resulted in an increase in fiber diameter, whereas raising the PEO concentration decreased fiber diameter. Additionally, elevating the total polymer and PEO content significantly increased the encapsulation efficiency (EE) % of RSV in the nanofibers. Moreover, higher levels of PEO positively influenced the swelling % and release efficiency (RE) %. The optimized RSV-loaded PAN/PEO nanofibers exhibited a smooth, cylindrical, and bead-free morphology with an average diameter of 217.36 ± 37.20 nm, an EE of 83.71 ± 2.28%, drug loading of 14.47 ± 1.09%, RE over 30 h of 60.95 ± 2.36%, swelling of 1111.67 ± 122.58%, ultimate tensile strength of 2.84 ± 0.34 MPa, and Young's modulus of 26.06 ± 5.58 MPa. The incorporation of Ag NPs resulted in bead-free fibers with a slightly reduced diameter and a swelling of 1032.5 ± 106.45%.X-ray diffraction analysis confirmed the crystalline presence of both RSV and Ag NPs within the fibers. The Ag NPs imparted strong antibacterial activity, producing inhibition zones against <i>Escherichia coli</i> (31.66 ± 2.51 mm) and <i>Staphylococcus aureus</i> (18.33 ± 3.51 mm), whereas RSV alone showed no antibacterial effect. <i>In vivo</i> wound healing studies demonstrated a significantly faster wound healing rate for Ag NPs-RSV- nanofiber compared to other groups, with complete wound closure, full re-epithelialization, enhanced collagen deposition, and the formation of skin appendages by day 15. These findings suggest that RSV-loaded PAN/PEO nanofibers offer a promising medicated wound dressing capable of promoting tissue regeneration and preventing infection.