Essay: Epithelialization

Towards the end of the inflammatory phase, the proliferation phase begins. During this phase, the tissue is reconstructed and new blood vessels are formed (Mostafa et al. 2006). Normally it last from day 4-21 after injury (Gurtner 2006).
Towards the beginning of the proliferative phase, approximately 3-5 days after injury, formation of granulation tissue begins (Enoch & Leaper 2005). Granulation tissue contains macrophages, fibro-blasts, and endothelial cells (Gurtner 2006). As mentioned earlier, fibroblasts are attracted to the wound 2-4 days after injury, by growth factors such as PDGF and TGF-??. The fibroblasts prolifer-ate and produce components of the extracellular matrix, such as collagen and proteoglycans, which fills the wound (Enoch & Leaper 2005). Basic fibroblast growth factor, PDGF, interleukin-1, TGF-??, and tumour necrosis factor stimulate collagen synthesis (Enoch & Leaper 2005). The level of collagen increases rapidly after day 5, but stabilizes after ~3 weeks. The collagens align to create fibers and fibril, which provide strength to the wound (Mostafa et al. 2006). Different types of collagen are synthesized forming the fibrils. Collagen I, III, and V are the major components of the connective tissue in a healing wound. Type IV collagen becomes part of the basement membrane (Enoch & Leaper 2005).
During granulation tissue formation, new blood vessels are formed from pre-existing vessels, a process known as angiogenesis (Enoch & Leaper 2005). During angiogenesis, endothelial cells are activated and the basement membrane of the parent vessel is degraded allowing a capillary sprout to form. Endothelial cells migrate through the created gap and towards angiogenic stimuli. These cells then divide and mature into new blood vessels (Enoch & Leaper 2005; Mostafa et al. 2006).
Angiogenesis is at first induced by fibroblast growth factor 2 (FGF-2). Hereafter further stimuli are by vascular endothelial growth factor (VEGF) which is produced by fibroblasts, macrophages and keratinocytes (Mostafa et al. 2006). Formation of new blood vessels is crucial for wound healing, because they are needed for delivery of nutrients and oxygen to the reparative cells at the site of injury (Johnson & Wilgus 2014).
During epithelialization, which begins a few hours after injury, epiboly takes place, where keratino-cytes from the wound edge migrates to cover the exposed area, as seen in figure 3 (Enoch & Leaper 2005; Gurtner 2006). Approximately 48 hours after injury, enlargement of epidermal cells along the edge of the wound occur. These cells begin to proliferate, thereby producing more migrating cells. When two migrating cells meet, further migration is inhibited. These cells, now making up the epithelial monolayer, differentiate and re-establish the epithelium (Mostafa et al. 2006). The epithe-lialization last until the end of the proliferation phase.