Pathology chapters
Repair, regeneration and wound healing
How tissues repair themselves by regeneration or scarring, the labile, stable and permanent cells, granulation tissue, healing by first and second intention, wound contraction, the factors that delay healing, and complications such as keloids and dehiscence.
- Tissue repair happens by regeneration (replacing lost cells with the same type: labile and stable tissues) or by scarring (fibrous tissue: permanent cells such as heart muscle and neurons).
- Granulation tissue (new capillaries, fibroblasts and inflammatory cells in loose matrix) is the hallmark of healing; collagen type III is laid down first and replaced by type I.
- First intention: clean, closely opposed wound (surgical incision), little scar; second intention: large gap, more granulation tissue, wound contraction by myofibroblasts, bigger scar; infection is the commonest cause of delayed healing.
On this page
Overview
After injury, the body restores tissue by:
- Regeneration: lost cells are replaced by the same type of cells, restoring normal structure and function.
- Repair by connective tissue (scarring): damaged tissue is replaced by fibrous tissue when cells cannot regenerate or the supporting framework is destroyed.
Most healing involves both.
Cell types by ability to divide
| Type | Behaviour | Examples | Healing |
|---|---|---|---|
| Labile (continuously dividing) | Constantly replaced from stem cells | Skin epidermis, gut lining, bone marrow, lining of ducts | Excellent regeneration |
| Stable (quiescent) | Normally resting; divide when stimulated | Liver, kidney tubules, pancreas, endothelium, fibroblasts, smooth muscle | Regenerate if the framework is intact |
| Permanent (non-dividing) | Cannot divide in adult life | Neurons, cardiac muscle (skeletal muscle has very limited regeneration via satellite cells) | Scar formation |
Heart muscle and neurons are permanent cells; a myocardial infarct or brain injury heals by scarring (fibrosis in the heart, gliosis in the brain).
The liver can regenerate (stable cells), but if its connective tissue framework is destroyed (cirrhosis), regeneration is disorganised into nodules with fibrosis.
Growth factors
- PDGF: attracts and stimulates fibroblasts and smooth muscle.
- VEGF: stimulates angiogenesis.
- FGF: angiogenesis, fibroblast growth.
- TGF-β: fibrosis (collagen synthesis) and dampens inflammation; the most important fibrogenic factor.
- EGF: epithelial cell growth.
Steps in repair by scarring
- Inflammation: removes debris and microbes (days 1–3).
- Proliferation: granulation tissue forms (from about day 3–5): angiogenesis, fibroblast migration and proliferation, collagen deposition; re-epithelialisation.
- Remodelling (maturation): weeks to months; collagen is reorganised and cross-linked; the scar becomes paler and stronger.
Granulation tissue
The hallmark of healing. Named for its pink, soft, granular appearance on the surface of wounds.
Microscopy: new thin-walled capillaries (angiogenesis), proliferating fibroblasts, and inflammatory cells in a loose, oedematous matrix.
It bleeds easily because the new vessels are fragile and leaky. Excess granulation tissue that protrudes above the wound is "proud flesh" (exuberant granulation).
Granulation tissue = new capillaries + fibroblasts + inflammatory cells. It is not the same as a granuloma.
Collagen
Type III collagen is laid down first; it is gradually replaced by stronger type I collagen during remodelling. Vitamin C is needed for collagen cross-linking.
Healing of skin wounds
Healing by first intention (primary union)
A clean, closely opposed wound with little tissue loss: a surgical incision closed with sutures.
| Time | Events |
|---|---|
| 24 hours | Clot fills the gap; neutrophils arrive; epithelium starts to grow from the edges |
| 24–48 hours | Epithelial cells meet under the scab, forming a thin continuous layer |
| Day 3 | Macrophages replace neutrophils; granulation tissue begins |
| Day 5 | Granulation tissue fills the gap; neovascularisation is maximal; collagen bridges the incision |
| Week 2 | Collagen and fibroblasts increase; inflammation and swelling settle; scar is pale |
| End of month 1 | A cellular connective-tissue scar covered by normal epidermis; skin appendages lost in the line of the scar do not regrow |
Healing by second intention (secondary union)
A large wound with gaping edges or tissue loss: ulcers, abscess cavities, infected or large traumatic wounds, burns.
Differences from first intention:
- More inflammation (more debris and fibrin to remove).
- Much more granulation tissue.
- Wound contraction by myofibroblasts (fibroblasts with contractile features), which can reduce the wound size by a large amount within weeks.
- Larger scar; slower healing.
Wound contraction is a feature of second intention healing, caused by myofibroblasts.
Cicatrisation is the final shrinking and hardening of the scar, which can cause contractures.
Wound strength
- About 10% of normal skin strength at 1 week (when sutures are often removed).
- Rises rapidly over the next 4 weeks.
- Reaches about 70–80% of normal at about 3 months, and never regains full strength.
Factors that influence healing
| Local factors | Systemic factors |
|---|---|
| Infection (the commonest cause of delayed healing) | Diabetes |
| Poor blood supply (ischaemia, varicose veins) | Malnutrition (protein, vitamin C, zinc) |
| Foreign bodies (sutures, dirt) | Corticosteroids (reduce inflammation and collagen synthesis) |
| Movement and mechanical stress | Old age, anaemia, poor circulation |
| Size, site and type of wound | Immunosuppression, chemotherapy, radiation |
| Haematoma, dead tissue | Smoking, obesity, jaundice |
Complications of wound healing
| Complication | Features |
|---|---|
| Deficient scar formation | Wound dehiscence (wound bursts open, especially abdominal wounds after surgery, with raised abdominal pressure from coughing or vomiting); ulceration in poorly perfused tissue |
| Excessive scar formation | Hypertrophic scar: raised scar that stays within the original wound; may regress. Keloid: excess collagen that grows beyond the wound edges and does not regress; commoner in darker skin; tends to recur after excision |
| Exuberant granulation (proud flesh) | Protrudes above the skin; blocks re-epithelialisation |
| Contracture | Excessive contraction causing deformity and limited movement, especially after burns across joints |
| Others | Implantation (epidermoid) cysts, pigment changes, rarely malignant change in a long-standing scar or ulcer (Marjolin ulcer, squamous cell carcinoma) |
Hypertrophic scar stays within the wound; keloid spreads beyond it.
Healing in special tissues
- Bone fracture: haematoma → soft callus (granulation tissue, cartilage) → hard callus (woven bone) → remodelling.
- Liver: regeneration if the framework is intact; cirrhosis if not.
- Heart: scar after myocardial infarction.
- Brain: gliosis (astrocytes), not fibrous scar.
- Nerves: peripheral axons regrow along their sheaths (about 1 mm/day).
Expect: labile, stable and permanent cells with examples, growth factors (VEGF, TGF-β), the composition of granulation tissue, collagen type III then I, the timeline of first-intention healing, first vs second intention, myofibroblasts and wound contraction, wound strength at 1 week and 3 months, factors delaying healing, and keloid vs hypertrophic scar.
Quick revision
- Labile (skin, gut, marrow), stable (liver, kidney), permanent (neurons, heart).
- Granulation tissue: new capillaries, fibroblasts, inflammatory cells.
- Collagen III first, then I; vitamin C needed.
- First intention: clean incision, little scar. Second: large gap, contraction (myofibroblasts), more scar.
- Strength: 10% at 1 week; 70–80% at 3 months.
- Infection is the commonest cause of delayed healing.
- Hypertrophic scar within the wound; keloid beyond it.
Written by The House Job from standard pathology references (Robbins and Cotran Pathologic Basis of Disease is the book named in the UHS PGET syllabus).
FAQ
What is granulation tissue?
Newly formed tissue in a healing wound made of new capillaries, proliferating fibroblasts and inflammatory cells in a loose matrix.
What is the difference between healing by first and second intention?
First intention occurs in clean wounds with closely opposed edges and leaves a small scar; second intention occurs in large or gaping wounds, with more granulation tissue, wound contraction and a larger scar.
Which cells cause wound contraction?
Myofibroblasts.
What is the commonest cause of delayed wound healing?
Infection.