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Phases of wound healing

• The four main stages of wound healing are:
  • Haemostasis
  • Inflammation
  • Regeneration
  • Repair
• These stages are not discrete but overlap

Haemostasis

• Damaged endothelial lining exposes platelets to sub-endothelial collagen
• Damaged endothelium releases von-Willebrand factor and tissue thromboplastin
• von-Willebrand factor facilitates platelet adhesion to sub-endothelial collagen
• Adhered platelets release ADP and thromboxane A2
• This leads to further platelet aggregation
• Tissue thromboplastin activates the coagulation pathways
• Fibrin is the end product of the coagulation pathways
• Fibrin forms a plug into which platelets and red blood cells are trapped
• This results in clot formation

Inflammation

• Platelets release platelet derived growth factor and transformation growth factor β
• These are chemotactic to neutrophils and monocytes
• Neutrophils and macrophages phagocytose foreign material and bacteria

Regeneration and repair

• Platelet derived growth factor and transformation growth factors are mitogenic to epithelium and fibroblasts
• This lead to proliferation of epithelial cells and fibroblasts
• Fibroblasts produce collagen
• Vascular endothelial growth factor is mitogenic to endothelial cells
• It is released by monocytes in response to hypoxia
• It promotes angiogenesis
• Wound strength by the end of 1st week is 10% of the original
• By the end of 3rd month it reaches 70% and thereafter plateaus

Time Line of events

• Within first 24 hours
  • Neutrophils are the predominant cell type
  • This is the phase of acute inflammation
  • Epithelial cells start proliferating and migrating into the wound cavity
• By the 2nd and 3rd day
  • Macrophage and fibroblasts are the dominant cell types
  • Epithelial cell proliferation and migration continues
  • Angiogenesis begins
  • Granulation tissue appears
  • Collagen fibres are present but these are vertical
  • They do not bridge the wound gap
  • Granulation tissue comprises newly formed new capillary loops
• By the end of 5th day
  • Fibroblasts are the predominant cell type
  • They synthesise collagen
  • Collagen now bridges the wound edges - bridging collagen
  • Epidermal cells continue division and epidermis is now multi-layered
  • Abundant granulation tissue is present
• During 2nd week
  • Acute inflammation begins to reduce
  • Collagen continues to accumulate

Aberrations in wound healing

Keloid scar

• Overgrowth of scar tissue
• Scar tissue extends beyond wound margin
• More common in black races
• Uncommon in children
• Typical sites are sternum, back, ear lobes
• Triamcinolone injections directly into the tissue is the initial treatment
• Other option is excision of the overgrowth
• They tend to recur

Hypertrophic scar

• Overgrowth of scar tissue but it does not extend beyond wound edge
• Can occur in any race
• More common in children
• Usually growth subsides with time
• May even regress
• More common over flexor surfaces and after burns

Author:  Dr Shakeeb Khan

Last updated: 05 January 2008

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