Wound Healing Stages

• Phases of normal wound healing

  • Hemostasis
  • Inflammation
  • Proliferation
  • Remodeling
• Fibrin mesh


  • Achieves hemostasis
  • Serves as scaffolding for migration of inflammatory cells
• Platelets


  • Release PDGF, PAF, TGF, fibrinectin to initiate wound repair
  • Release serotonin to facilitate inflammatory cell migration
• Inflammation


  1. Neutrophils infiltrate wound site, peak at 24-48 hours

  2. Macrophages appear 72 hours after injury, play regulatory roles
• Angiogenesis


  • Endothelial cells proliferate to form new blood vessels from pre-existing blood vessels
• Granulation


  • Growth factors attract fibroblasts
  • Fibroblasts produce matrix of adhesive proteins, proteoglycans, glycosaminoglycans, collagen and elastin
• Re-epithelialization


  • Surrounding keratinocytes proliferate and migrate to re-establish barrier function
• Factors that can impair wound healing

  • Local factors: Wound type, size, location, pressure, edema, dehydration, blood supply, infection, foreign material
  • Systemic factors: Age, medications, comorbidities, nutritional deficiencies
• Primary intention healing


  Wound edges sutured or stapled, heals quickly with minimal tissue loss
• Secondary intention healing


  Wound sides not opposed, heals from bottom up, involves granulation and re-epithelialization
• Myofibroblasts play a major role in secondary intention wound healing
• Healing


  Cellular response to restore structural & functional integrity by replacement with fibrous tissue (repair by scar)
• Healing process


  1. Hemostasis

  2. Inflammatory (early stages, first two weeks)

  3. Proliferative

  4. Remodelling/Maturation (late stage, continue over months to years)
• Hemostasis sequence


  1. Vasospasm/vasoconstriction

  2. Formation of platelet plug (primary hemostasis)

  3. Formation of fibrin clot (secondary hemostasis)
• Hemostasis


  • Reduces blood loss & facilitates platelet accumulation
  • Platelets release PDGF, TGF-β, PAF, fibronectin to initiate wound healing
  • Injured endothelial cells & tissue's immune cells promote inflammatory response
• Inflammatory stage sequence


  1. Neutrophils first to reach site of injury via chemotaxis

  2. Macrophages present at site, phagocytosis, stimulate/activate fibroblast, release growth factors & cytokines
• Proliferative stage sequence


  1. Angiogenesis - formation of new blood vessels

  2. Granulation - formation of soft, beefy red, granular area

  3. Re-epithelisation - re-establish barrier function
• Proliferative stage


  • Angiogenesis promoted by cytokines & growth factors (TNF-α, TGF-β, VEGF)
  • Granulation tissue with collagen (lll)foundation for extracellular matrix synthesis
  • Re-epithelialisation : Keratinocytes proliferate & migrate across damaged area
• Angiogenesis sequence


  Pericytes separate, macrophages release VEGF, VEGF attaches to endothelial cells, endothelial cell proliferation, lumen appears, fusion of tip cells, anastomosis occurs
• Angiogenesis


  • Endothelial cell migration & proliferation promoted by VEGF & MMPs
  • Pericytes recruited to form mature blood vessel promoted by PDGF & TGF-β
• Remodelling/Maturation sequence


  Extracellular matrix accumulation, fibroblasts mature into myofibroblasts, reorganisation of ECM & collagen, acellular scar tissue forms, myofibroblasts naturally die off via apoptosis