Biomolecular and cellular effects in skin wound healing: the association between ascorbic acid and hypoxia-induced factor

The skin serves as a barrier to protect the body from environmental microorganisms and is the largest tissue of the body and any damage must be quickly and effectively repaired. The fundamental purpose of dermal fibroblasts is to produce and secrete extracellular matrix, which is crucial for healing wounds. The production of collagen by dermal fibroblasts requires the cofactor ascorbic acid, a free radical scavenger. In skin wounds, the presence of Ascorbic acid (AA) decreases the expression of pro-inflammatory factors and increases the expression of wound-healing factors. In addition, AA plays an important role in all three phases of wound healing, including inflammation, proliferation, and regeneration. On the other hand, growing evidence indicates that hypoxia improves the wound healing performance of mesenchymal stem cell-conditioned medium compared to the normoxic-conditioned medium. In a hypoxic-conditioned medium, the proliferation and migration of endothelial cells, fibroblasts, and keratinocytes (important cells in accelerating skin wound healing) increase. In this review, the role of AA, hypoxia, and their interactions on wound healing will be discussed and summarized by the in vitro and in vivo studies conducted to date. GRAPHICAL ABSTRACT: [Image: see text]