Idebenone-loaded wound dressings promote diabetic wound healing through downregulation of Il1b, Nfkb genes and upregulation of Fgf2 gene

Abstract

Reactive oxygen species (ROS) are overproduced in diabetic wounds and retard the healing response. Considering the antioxidative function of idebenone, its exogenous administration may quench excessive ROS and promote diabetic wound healing. In the current study, idebenone was loaded into polyvinyl alcohol (PVA) /calcium alginate scaffolds at three different concentrations of 1 w/w%, 2 w/w%, and 3 w/w%. Various in vitro experiments were performed to characterize the developed wound dressings. Cell viability assay showed that scaffolds loaded with 1 w/w% idebenone had significantly better protection under oxidative stress and exhibited higher cell viability. Therefore, the dressings containing 1% drug was chosen to treat diabetic wounds in rat model. Wound healing assay showed that the dressings loaded with 1% drug had significantly higher rate of wound size reduction, collagen deposition, and epithelial thickness. Gene expression study showed that wound healing was accompanied by modulation of inflammatory response, protection against oxidative stress, and increasing angiogenesis-related genes. This preliminary research suggests that PVA/calcium alginate/1% idebenone scaffolds can be considered as a potential treatment modality to treat diabetic wounds in the clinic. However, more extensive studies at gene and protein expression levels are required to understand its exact mechanism of healing effects.