Wound healing process

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wound healing phases hemostasis inflammation proliferation remodeling authoritative

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Wound healing process

Wound healing is a coordinated, overlapping sequence that restores tissue integrity after injury. It is commonly divided into four phases:
PhaseApproximate timingMain events
1. HemostasisImmediate to hoursVasoconstriction, platelet plug, fibrin clot formation
2. InflammationHours to about 3-5 daysNeutrophils and macrophages remove bacteria, debris, and damaged tissue
3. ProliferationAbout day 3 to several weeksGranulation tissue, angiogenesis, fibroblast collagen synthesis, epithelialization, wound contraction
4. Maturation/remodelingBegins around week 3, lasts months to a year or moreCollagen is reorganized and scar strength gradually increases

1. Hemostasis

  • Injury causes vasoconstriction to reduce bleeding.
  • Platelets adhere and aggregate, forming an initial plug.
  • The coagulation cascade creates a fibrin mesh, stabilizing the clot.
  • Platelets release growth factors, including PDGF and TGF-beta, which recruit inflammatory cells and fibroblasts.

2. Inflammatory phase

  • Initially, blood vessels become more permeable, producing redness, warmth, swelling, and mild pain.
  • Neutrophils arrive first and help remove bacteria and necrotic material.
  • Macrophages then become predominant. They clear debris and release cytokines and growth factors that drive repair.
  • Excessive or prolonged inflammation, such as with infection or poor perfusion, delays healing.

3. Proliferative phase

This phase rebuilds the wound.
  • Angiogenesis: New capillaries grow into the wound, giving granulation tissue its pink-red, granular appearance.
  • Fibroplasia: Fibroblasts produce extracellular matrix and predominantly type III collagen.
  • Epithelialization: Keratinocytes migrate from wound edges and skin appendages to cover the surface.
  • Contraction: Myofibroblasts pull the wound edges inward, especially in wounds healing by secondary intention.

4. Maturation or remodeling phase

  • Type III collagen is progressively replaced by stronger, more organized type I collagen.
  • Collagen fibers cross-link and align along stress lines.
  • Vascularity decreases, so the scar becomes flatter and paler.
  • A healed wound does not regain the tensile strength of unwounded skin. The mature scar typically reaches about 70-80% of original tensile strength.

Types of wound healing

  1. Primary intention
    • Clean wound with edges approximated, such as a sutured surgical incision.
    • Minimal tissue loss, less granulation tissue, faster healing, and generally a smaller scar.
  2. Secondary intention
    • Wound is left open because of tissue loss, contamination, or inability to approximate edges.
    • Healing occurs through granulation, contraction, and epithelialization.
    • Slower healing and larger scar.
  3. Tertiary intention or delayed primary closure
    • Wound is initially left open, often because it is contaminated or infected.
    • It is closed later once contamination and inflammation are controlled.
Primary healing involves prompt reapproximation of wound edges with sutures, staples, tape, or adhesive, whereas secondary healing is associated with more contraction and a higher likelihood of scar widening or breakdown at mobile areas. Bailey and Love's Short Practice of Surgery, p. 706.

Factors that delay wound healing

  • Infection or foreign body
  • Poor blood supply, ischemia, edema, or hypoxia
  • Diabetes mellitus
  • Malnutrition, especially protein, vitamin C, or zinc deficiency
  • Smoking
  • Corticosteroids, chemotherapy, and immunosuppression
  • Anemia, advanced age, obesity
  • Excess tension, repeated trauma, pressure, or poor wound care
The phases overlap rather than occurring as rigid separate stages. The NCBI wound-healing review describes inflammation, granulation tissue formation, re-epithelialization, and remodeling as coordinated processes, with remodeling continuing for many months.
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