Healing by repair | Steps Of Scar Formation

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Q List the steps involved in wound healing by repair

A)  Steps involved in wound healing by Repair are:-

      1. Tissue injury 
        • Healing may be either by regeneration/repair or both.
        • Mild and transient injury results in regeneration and if cell damage persists, the wound heals by scar formation and fibrosis.
      2. Inflammation occurs
        • Macrophages function to clear offending dead tissue, provide growth factors and secrete cytokines that stimulate fibroblast proliferation, connective tissue synthesis, and deposition.
      3. Inflammatory reactions try to limit the damage and remove the injured tissue.
      4. This injured tissue has to be replaced by the living tissue which is done by a transient increase in cellularity by cellular proliferation.
      5. Cellular proliferation is characterized by DNA replication and mitosis where cells undergo various phases of the cell cycle to give rise to 2 daughter cells.
      6. To learn about Mitosis, click here 
      7. G1/S and G2/M checkpoint checks DNA before and after replication respectively.
      8. Inflammation results in angiogenesis
        • Vascular endothelial cell growth factor(VEGF) and NO results in increased vascular permeability.
        • Separation of pericytes from Basement membrane.
        • Basement membrane breaks down and facilitates the formation of vessel sprout ( results from endothelium proliferation).
        • FGFs cause migration, proliferation, and maturation of endothelial cell towards the site of injury.
        • Remodeling of the endothelial cell to form capillary sprouts/tubes( guided by pericytes towards injury).
        • Elongation of vascular stumps.
        • Recruitment of pericytes and smooth muscle cells to form the peri-endothelial cells results in maturation of vessel.
        • Finally, blood vessels sprouts will fuse with other sprouts to build new circulatory systems.
      9. For 2-3 days, the proliferation of fibroblast and endothelial cells results in the formation of granulation tissue(the hallmark of tissue repair)
        • Microscopy of granulation tissue shows leaky new small blood vessels(product of angiogenesis) that permits leakage of plasma proteins in extracellular space resulting in edema.
        • Proliferating fibroblast
      10. Increased accumulation of collagen
      11. Granulation tissue converted to pale avascular scar composed of spindle-shaped fibroblast, dense collagen, fragments of elastic tissue, etc
      12. By the end of one month, scar formation completes and inflammation ceases.

Q) List steps involved in the healing of a wound by the Primary union or First Intention

A)Steps involved in the healing of a wound by the Primary union or First Intention are

      1. Healing by 1st intention means healing of a clean and uninfected surgical incision in the skin joined by surgical sutures which involve the minimal death of the epithelial cell and connective tissue and minimal disruption of the basement membrane.
      2. Formation of a blood clot with trapped RBCs, fibrin, fibronectin and complement components in between sutured margins in the first 24 hrs.
      3. Clot stops bleeding.
      4. Dehydration of the external surface of clot leads to the formation of scab over the wounds.
      5. Neutrophil infiltrates at margins.
      6. Neutrophils release proteolytic enzymes which clean out debris.
      7. Basal cells of epidermis at both cut ends turn mitotic.
      8. Epithelial cells from both edges of wound proliferate.
      9. These cells migrate across the wound.
      10. After 2 days neutrophils are replaced by macrophages.
      11. Epithelial cells fuse in midline and continuity is re-established.
      12. Within 3-7 days granulation tissue begins to invade incision space.
      13. Granulation tissue grows to fill the wound by 5-7 days.
      14. Surface epidermis becomes evenly thickened.
      15. Acute inflammatory response subsides.
      16. Leukocyte infiltrates, edema and angiogenesis disappear during the 2nd week.
      17. Increased accumulation of collagen.
      18. Granulation tissue converted to pale avascular scar.
      19. Wound gradually achieves 80% of its tensile strength of normal skin with few months.

Q) List steps involved in the healing of a wound by the secondary union or second Intention

A) Steps involved in the healing of a wound by the secondary union or second Intention are

      1. Healing of wound by secondary union means healing of a cutaneous wound with a large defect (such as in a laceration
        and contusion), irregular margins and extensive loss of cells and tissue with more exudate and necrotic tissue.
      2. Large clot/scab is formed
      3. Bleeding is stopped
      4. Severed inflammatory rxn
      5. Abundant granulation tissue at the site of the wound
      6. Extensive deposition of collagen
      7. Scar formation
      8. Myofibroblasts mediate wound contraction(characteristic of healing by secondary intention). This decreases the gap between dermal edges of the wound and reduces the wound surface area.

Wound strength

      • Type I collagen is responsible for the development of strength
      • 10% after the 1st week
      • First increases quickly and then slow down during the next 4 weeks
      • 70-80% at the end of 3rd month

Q) How does healing of a wound by the secondary union and primary union differ?


Primary Intention

Secondary Intention

Clean surgical wound


Clean margins


No infection

mostly Infected

Scanty granulation tissue

Abundant; fills the gap

Complications are rare

Infection and suppuration

Healing results in neat linear scar

Healing results in irregular contracted scar

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