The first phase of hemostasis begins immediately after wounding, with vascular constriction and fibrin clot formation. In adult humans, optimal wound healing involves the following the events: (1) rapid hemostasis (2) appropriate inflammation (3) mesenchymal cell differentiation, proliferation, and migration to the wound site (4) suitable angiogenesis (5) prompt re-epithelialization (re-growth of epithelial tissue over the wound surface) and (6) proper synthesis, cross-linking, and alignment of collagen to provide strength to the healing tissue ( Gosain and DiPietro, 2004 Mathieu et al., 2006). Interruptions, aberrancies, or prolongation in the process can lead to delayed wound healing or a non-healing chronic wound. The events of each phase must happen in a precise and regulated manner. Wound healing is a dynamic process consisting of four continuous, overlapping, and precisely programmed phases. This review will discuss the many different factors that affect cutaneous wound healing and the potential cellular and molecular mechanisms involved. While much remains to be learned, these studies may lead to therapeutics that will promote proper tissue repair and improve impaired wound healing. More recently, a great deal of research has been directed at understanding the critical factors that influence poorly healing wounds. Laboratory investigations and clinical studies have yielded a wealth of information about both normal and impaired wound healing. Non-healing wounds result in enormous health care expenditures, with the total cost estimated at more than $3 billion per year ( Mathieu et al., 2006 Menke et al., 2007). Non-healing wounds affect about 3 to 6 million people in the United States, with persons 65 years and older accounting for 85% of these events. Most chronic wounds are ulcers that are associated with ischemia, diabetes mellitus, venous stasis disease, or pressure. Such wounds frequently enter a state of pathologic inflammation due to a postponed, incomplete, or uncoordinated healing process. Wounds that exhibit impaired healing, including delayed acute wounds and chronic wounds, generally have failed to progress through the normal stages of healing.
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