wound healing

• Tissue regeneration


  The regeneration of injured cells and tissues involves cell proliferation, which is driven by growth factors and is critically dependent on the integrity of the extracellular matrix, and by the development of mature cells from stem cells
• Tissues classified by proliferative capacity

  • Labile (continuously dividing) tissues
  • Stable tissues
  • Permanent tissues
• Labile tissues


  • Cells are continuously being lost and replaced by maturation from tissue stem cells and by proliferation of mature cells. Examples: hematopoietic cells, surface epithelia, exocrine organ ducts, gastrointestinal tract, urinary tract
• Stable tissues


  • Cells are quiescent (in the G0 stage of the cell cycle) and have only minimal proliferative activity in their normal state, but are capable of dividing in response to injury or loss of tissue mass. Examples: liver, kidney, pancreas, endothelial cells, fibroblasts, smooth muscle cells
• Permanent tissues


  • Cells are terminally differentiated and non-proliferative in postnatal life. Examples: neurons, cardiac muscle cells
• Injury to the brain or heart is irreversible and results in a scar, because neurons and cardiac myocytes cannot regenerate
• Skeletal muscle is usually classified as a permanent tissue, but satellite cells attached to the endomysial sheath provide some regenerative capacity for muscle
• Scar formation


  A response that "patches" rather than restores the tissue, involving the replacement of injured cells with connective tissue
• Tissue repair by connective tissue deposition

  1. Angiogenesis (formation of new blood vessels)

  2. Formation of granulation tissue

  3. Remodeling of connective tissue
• Angiogenesis


  The formation of new blood vessels, which supply nutrients and oxygen needed to support the repair process
• Granulation tissue


  Migration and proliferation of fibroblasts and deposition of loose connective tissue, together with the vessels and interspersed leukocytes
• Remodeling of connective tissue

  Maturation and reorganization of the connective tissue to produce the stable fibrous scar
• Healing by first intention

  When the injury involves only the epithelial layer, the principal mechanism of repair is epithelial regeneration
• Healing by second intention

  When cell or tissue loss is more extensive, the repair process involves a combination of regeneration and scarring
• Differences between healing by first and second intention

  • Larger fibrin clot, more exudate and necrotic debris
  • Much larger amounts of granulation tissue formed
  • Larger scar tissue formation
  • Wound contraction by myofibroblasts
• Factors that influence wound healing

  • Infection
  • Nutritional status
  • Glucocorticoids
  • Mechanical factors
  • Poor perfusion
  • Foreign bodies
  • Type and extent of tissue injury
  • Location of injury and tissue character
• Wound strength


  Carefully sutured wounds have approximately 70% of the strength of normal skin, increasing to 70-80% of normal by 3 months
• Fibrosis


  The excessive deposition of collagen and other ECM components in a tissue, a pathologic process induced by persistent injurious stimuli
• Fibrotic disorders


  • Liver cirrhosis
  • Systemic sclerosis
  • Fibrosing lung diseases
  • End-stage kidney disease
  • Constrictive pericarditis
• Abnormalities in tissue repair

  • Inadequate formation of granulation tissue or scar (wound dehiscence, ulceration)
  • Excessive formation of repair components (hypertrophic scars, keloids, exuberant granulation)
  • Formation of contractures