Wound Healing

Wound healing is a complex process that can be divided into three phases: (1) the inflammatory phase, (2) the proliferation phase, and (3) the remodeling phase (Yamaguchi and Yoshikawa, 2001). Progression through these phases requires coordinated involvement of blood vessels (exchange of platelets, macrophages, and neutrophils with tissue), epidermis (stimulation of keratinocytes, melanocytes, and Langerhans cells), dermis (activation of fibroblasts and myofibroblasts), nerves, and subcutaneous fatty layers (adipocytes). The effects of vitamin A on wound healing have long been recognized. Clinical and experimental studies have shown that vitamin A deficiency can impair wound healing (Hunt, 1986). In addition, treatment with vitamin A and other retinoids, through dietary supplementation or topical application, has been shown to enhance wound healing (Ehrlich and Hunt, 1968; Gerber and Erdman, 1982; Tom et al., 2005). While much about the biochemical and molecular mechanisms through which vitamin A enhances wound healing remains unknown, it is clear that events in all three phases of the wound healing process are affected by vitamin A and retinoids. Effects on the inflammatory and proliferation phases of wound healing have been observed and ostensibly involve regulation in the release of cytokines and growth factors in the skin (Muehlberger et al., 2005; Yuen and Stratford, 2004). Studies have shown that vitamin A and retinoic acid influence production of cytokines and facilitators of keratinocyte mobility, such plasminogen activator, as well as growth factors, such as transforming growth factor-;S1 and insulin-like growth factor-1 (Braungart et al., 2001; Wicke et al., 2000; Yuen and Stratford, 2004). Effects of vitamin A and retinoids on events associated with the remodeling phase of wound healing are well documented. Many of the events in remodeling at the site of a wound involve dermal fibroblasts and the synthesis of components in the extracellular matrix of the dermis (Pilcher et al., 1999; Yamaguchi and Yoshikawa, 2001). Retinoic acid has been shown to enhance production of extracellular matrix components such as collagen in cultured fibroblasts and during wound healing (Varani et al., 1993; Wicke et al., 2000).

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