Wound healing is the complex, dynamic process of restoration by which cellular structure and tissue arrangement are re-established following an incident of injury through a complex and highly coordinated series of interconnected events. Generally, the process of wound healing is divided into four sequential, yet overlapping phases: the hemostasis phase, the inflammatory phase, the proliferative phase and the remodeling phase. Homeostasis, the initial phase of wound healing that begins immediately after infliction of an injury, is the process by which blood flow is arrested or stagnated through the aggregation of platelets and the development of a fibrin clot, which in turn provides the structural support for the cellular constituents of inflammation. The subsequent inflammatory phase is initiated by the release of cytokines from these aggregating platelets, and entails the orchestrated delivery of leukocytes, and later macrophages, for the removal of any injurious stimuli and compromised tissue from the affected region. This phase concludes with the secretion of numerous factors responsible for initiating the migration and division of those cells destined for involvement in the proliferative phase. This third phase of wound healing is characterized by the formation of new blood vessels (angiogenesis), the excretion of collagen and fibronectin from a newly forming extracellular matrix, the proliferation and migration of epithelial cells, and wound contraction. Wound healing concludes with the fourth and final phase of remodeling. During remodeling, which can persist for many years following the initial incident of injury, the wound enters a state of constant alteration during which wound contraction progresses, superfluous cells are removed through apoptosis, and collagen is remodeled and deposited along tension lines. Under normal circumstances wound healing progresses through these four stages in a predictable and timely manner, culminating in the removal of any harmful agents and the replacement of normal skin to once again form a protective barrier against the external environment. However, the wound healing process is as fragile as it is complex, and it is therefore extremely susceptible to occurrences of dysfunction, which can result in instances of chronic wounds or pathological scarring.
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