1 Phases of Wound Healing

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  Coagulation (begins immediately after injury): Platelets adhere to exposed matrix via integrins that bind to collagen and laminin. Blood coagulation produces thrombin, which promotes platelet aggregation and granule release.

  
  
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  Inflammation (begins shortly thereafter): the platelet granules generate an inflammatory response. Inflammatory cells (neutrophils and macrophages) are attracted to the injury site and undergo activation. Macrophages secrete various growth factors, which in turn stimulate the infiltration, proliferation and migration of fibroblasts and endothelial cells, leading to angiogenesis and generation of antioxidants.

  
  
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  Within hours of injury, an epidermal covering composed predominantly of keratinocytes begins to migrate and undergo stratification and differentiation to reconstitute the barrier function of epidermis (epithelisation). It also promotes extracellular matrix production, growth factor and cytokine expression, and angiogenesis.

  
  
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  Overall, the inflammatory process is a defence against infections and a bridge between tissue injury and new cell growth.

  
  
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  Migratory and proliferation (begins within days): cells (mainly epithelial cells, fibroblasts, and endothelial cells) recruited undergo rapid mitosis and begin to define the ultimate structure of the scar.

  
  
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  Ultimately, with the synthesis of extracellular proteins and proteoglycans and a balance of collagen lysis and collagen synthesis, the remodelling of new tissue initiates. The processes are dependent on the availability of metabolic substrates, oxygen concentration and growth factors.

  
  
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  Remodelling (lasts up to a year): refers to changing patterns in the deposition of matrix components during wound healing.

  
  
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  Initially, the wound matrix consists of a clot of fibrin and fibronectin, resulting from haemostasis and macrophage activation. Over time, it changes to a mixture of glycosaminoglycans, proteoglycans and other proteins, which support the deposition of future matrix components. There is proliferation and migration of fibroblasts and collagen synthesis. Collagen fibres, originally thin and randomly oriented, gradually increase in thickness and, aided by proteinases, are rearranged along the stress line of the wound.

  
  
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  Remodelling contributes to the development of the tensile strength in the wound. Wounds gain 20% of their ultimate strength in three weeks and later gain more strength, but they never reach more than about 70% of the strength of normal skin.