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Granulation tissue and scar formation !

  • Process

When a gap cannot regrow, new vessels and fibroblasts fill it with pink, grainy tissue that slowly turns into a pale collagen scar.

Updated 2026-11-01

What it is

Scar formation follows a predictable sequence: inflammation cleans the injured area, new vessels and fibroblasts form granulation tissue, collagen is deposited, and the scar is remodelled over months. Granulation tissue, named for the pink, soft, grainy surface of an open wound, is the hallmark of healing; its formation and maturation explain wound strength, the timeline of an infarct and many healing disorders.

Structure

  • Granulation tissue, gross: bright red-pink, soft, grainy, bleeds easily.
  • Granulation tissue, H&E: many small new capillaries perpendicular to the surface, plump fibroblasts, oedematous matrix, macrophages and some neutrophils.
  • Mature scar, H&E: dense pink collagen bundles, few spindle-shaped fibroblasts, few vessels, no skin appendages.

Step by step

  1. Haemostasis: a clot of fibrin and platelets fills the defect and acts as scaffold; platelets release PDGF and TGF-β.
  2. Inflammation: neutrophils clear bacteria and debris; macrophages, the key cells, remove fibrin and secrete growth factors.
  3. Angiogenesis: VEGF and FGF-2 make capillaries sprout from existing vessels; they are leaky, so the new tissue is oedematous.
  4. Fibroblasts migrate and proliferate (PDGF, FGF-2, TGF-β) and lay down matrix, at first mostly type III collagen.
  5. Granulation tissue is visible by 3–5 days: capillaries, fibroblasts, loose matrix, macrophages.
  6. Collagen accumulates and vessels regress; myofibroblasts contract the wound.
  7. Remodelling over months: zinc-dependent metalloproteinases degrade collagen; type III is replaced by cross-linked type I.
  8. The mature scar is pale, poor in vessels and mostly type I collagen; it lacks skin appendages and never regains full strength.

Markers

  • Myofibroblasts: alpha-smooth muscle actin
  • Collagen: Masson trichrome (blue)
  • Early type III, late type I collagen
  • Vitamin C: prolyl and lysyl hydroxylases
  • Copper: lysyl oxidase
  • Zinc: metalloproteinases

Clinical notes

  • Excess granulation tissue bulging above the skin (proud flesh) blocks re-epithelialisation and may need removal.
  • In scurvy, poorly hydroxylated collagen makes wounds heal slowly and old scars can reopen.
  • In a myocardial infarct, granulation tissue is well developed at about 1–2 weeks and a dense scar has formed by about 2 months.

Test yourself

Think of the answer, then tap the question to see it.

What is granulation tissue made of?

New, leaky capillaries, proliferating fibroblasts and myofibroblasts, loose oedematous matrix and inflammatory cells, mainly macrophages.

Which collagen predominates early in a wound, and which in the mature scar?

Type III early; type I in the mature scar after remodelling.

Which growth factor matters most for collagen synthesis and fibrosis?

TGF-β.

Why is granulation tissue not the same as a granuloma?

Granulation tissue is healing vascular connective tissue; a granuloma is a nodule of activated macrophages in chronic inflammation.

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Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.

Sources: 4.6 Tissue Injury and Aging (OpenStax (Anatomy and Physiology 2e), 2022); Scurvy: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2026); Keloids: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2026).

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Representative model, for educational purposes only.