Wound Healing Overview

Wound Healing 2

• Wound healing involves four key steps: haemostasis, inflammation, proliferation/angiogenesis, and matrix remodelling.

Haemostasis

• The first stage of wound healing
• Stops bleeding after vascular damage
• Three main steps:
  • Vasoconstriction
  • Primary haemostasis
  • Secondary haemostasis

Inflammation

• The primary defence against pathogenic wound invasion
• A response of vascular tissues to infections and tissue damage, bringing necessary cells and molecules to the affected area.
• Characterised by dilation of small blood vessels and accumulation of leukocytes and fluid in the extravascular tissue.
• Morphologic hallmarks: oedema, redness, warmth, and swelling; pain
• Key players: neutrophils, macrophages, mast cells, monocytes
• Steps of inflammation (5 R's):
  • Recognition of the injurious agent
  • Recruitment of leucocytes
  • Removal of the agent
  • Regulation (control) of the response
  • Resolution (repair)
• Types of inflammation:
  • Acute (e.g., injury, infection):
    • Resolution: clearance of stimuli, inflammatory cells, and injured cells
    • Progression to chronic if not resolved (e.g., persistent injury, autoimmune)
    • Potential for pus formation (abscess)
  • Chronic (e.g., chronic infections, autoimmune):
    • Persistent inflammation, mononuclear cell infiltrate, and fibrosis (scar)
• Forms of inflammation
  • Serous: fluid leakage into tissues
  • Fibrinous: fibrin-rich exudate
  • Purulent: pus-forming (Images included in the slides show examples.)

Proliferation and Angiogenesis

• Occurs after inflammation subsides
• Angiogenesis: involves endothelial cell proliferation, migration, and branching to form new blood vessels.
• Pericytes provide structural integrity to endothelial cells.
• Growth factors (e.g., Fibroblasts Growth Factor (FGF), Transforming Growth Factor beta (TGF-β), Platelet-derived Growth Factor (PDGF), Vascular endothelial growth factor (VEGF),Keratinocyte growth factor (KGF), Insulin Growth factor (IGF)) are crucial.
• Growth factors produced by platelets and leukocytes drive the subsequent healing phases.
• Needed for tissue repair and wound closure

Matrix Remodelling

• The rebuilding of the ECM (extracellular matrix) part of the injury response
• Fibroblasts are dominant cells in this process—replacing the initial fibrin clot with components such as hyaluronan, fibronectin, and proteoglycans.
• The formation of mature collagen fibres leads to the formation of a scar.
• ECM never fully returns to that of unwounded skin.
• The granulation tissue (type III collagen-rich) is eventually replaced primarily by collagen type I, increasing tensile strength of the scar.

Summary

• Wound healing involves four essential phases: haemostasis (the initial step), inflammation (defence mechanism), proliferation/angiogenesis (building new tissue and vessels), and matrix remodelling (regenerating the extracellular matrix, scarring).
• Growth factors are important elements throughout each phase.