• Haemostasis
    • Clot stops bleeding
      • But also provides matrix rich in growth factors and chemokines
      • Acts as a scaffold for migrating leukocytes and stromal cells
  • Inflammation
    • Also get inflammatory vascular changes followed by inflammatory cell recruitment
      • Within 24hrs neutrophils appear at the margins
      • Begin process of wound sterilization and debris degradation
    • Granulation tissue
      • Within 1-2 days (peak 5-7 days)
      • Fibroblasts and endothelium form this
      • Highly vascularised loose connective tissue and hallmark of early tissue repair
      • Vessels leaky, therefore tissue oedema occurs
    • At this stage, wound strength will primarily rely on sutures
  • Proliferation
    • Migration and expansion of:
      • Endothelial cells (Angiogenesis)
      • Connective tissue cells (provisional matrix)
    • Within 2-4 days, neutrophils largely replaced by macrophages
      • Become main cellular elements in clearing debris and directing subsequent angiogenesis and ECM deposition
    • Eventually granulation tissue scaffolding is converted to scar composed of fibroblasts and collagen
      • Fibroblast migration and proliferation driven by macrophages
        • TGF-β most important fibrogenic agent
    • After 2 weeks, scar formation (collagen deposition) is the most dominant feature
      • Get regression of the vasculature
      • Granulation tissue all converted to avascular scar, without inflammation, covered by intact epithelium
    • Get rapid increase in wound strength to 30-50%
  • Remodeling Phase
    • Constant absorption and replacement of collagen along the lines of stress
    • Wound contraction accomplished by myofibroblasts
      • Have synthetic function of fibroblasts
      • Also contractile capability of smooth muscle cells
      • Cause decreased surface area of the wound
    • Remodelling/change in ECM deposition
  • Strength of Wound Over Time
    • Initially dependent on suturing
    • At 1 week (when sutures removed)
      • Typically has 10% strength of normal
    • Tensile strength eventually plateaus at 70-80% of normal at 3 months
      • Associated with increased collagen synthesis exceeding collagen degradation
      • Followed by cross-linking and increased fibre size