Nanofibrous wound dressings loaded with 3-hydroxyanthranilic promote diabetic wound healing via upregulation of <i>b-FGF</i> gene and downregulation of glutathione peroxidase and <i>IL-1β</i> genes

Diabetic wounds are associated with prolonged inflammation and impaired healing due to the overproduction of reactive oxygen species (ROS). These reactive molecules damage cellular components and the extracellular matrix, delaying tissue regeneration. Addressing oxidative stress in the wound microenvironment is a promising strategy to improve healing outcomes. To mitigate ROS at the wound site, 3-hydroxyanthranilic acid (3HA), a known antioxidant, was incorporated into polyvinyl alcohol (PVA) electrospun scaffolds at concentrations of 0.5%, 1%, and 1.5% (w/w). The scaffolds were characterized for fiber morphology and diameter. In vitro cell viability assays were performed under both normal and oxidative stress conditions using fibroblasts. The optimal formulation was further evaluated in a streptozotocin-induced diabetic rat wound model. Gene expression analysis of Interleukin-1 beta (IL-1β), glutathione peroxidase, and basic fibroblast growth factor (b-FGF) was conducted using qPCR. The incorporation of 3HA did not significantly alter the nanofiber morphology. The average fiber diameter was 1408.18 ± 31.28 nm for PVA/1%3HA and 1395.61 ± 23.09 nm for pure PVA scaffolds. Among all formulations, the scaffold with 1% 3HA demonstrated the highest cell viability under oxidative stress. In vivo wound healing studies revealed that PVA/1% 3HA-treated wounds closed more rapidly compared to the PVA-only and untreated control groups. Gene expression results showed reduced levels of IL-1β and glutathione peroxidase, while b-FGF expression was significantly upregulated in the treated group. The PVA/1% 3HA scaffold effectively enhanced diabetic wound healing by reducing oxidative stress and inflammation while promoting tissue regeneration. The improved healing outcomes can be attributed to the antioxidant and immunomodulatory effects of 3HA. These results support the potential of 3HA-loaded PVA scaffolds as a bioactive dressing for diabetic wound management.