How wound healing is tested on Step 1
Expect questions on the day a given cell or collagen type predominates, a deficiency that impairs healing (vitamin C, zinc, copper), a growth factor's role, or the difference between a keloid and a hypertrophic scar.
Labile and stable tissues with an intact framework can regenerate. When cells cannot divide (myocardium, neurons) or the framework is destroyed, the tissue repairs with a fibrous scar.
The four phases
Healing phases overlap rather than switch on and off. Each has a dominant cell and a set of signals that recruit the next.
| Phase | Timing | Key cells and events |
|---|---|---|
| Hemostasis | Minutes | Vasoconstriction, platelet plug, fibrin clot; platelets release PDGF and TGF-β |
| Inflammation | Days 1–3 | Neutrophils first (24–48 h), then macrophages clear debris and secrete growth factors |
| Proliferation | Day 3 to ~3 weeks | Fibroblasts lay down type III collagen; angiogenesis (VEGF, FGF); re-epithelialization; myofibroblasts contract the wound |
| Remodeling (maturation) | Week 3 to 1+ year | Type III replaced by type I collagen; cross-linking increases tensile strength; metalloproteinases (need zinc) remodel matrix |
A healed incision regains about 70–80% of the tensile strength of uninjured skin by about 3 months and never fully returns to normal.
Growth factors and collagen
Growth factors coordinate the switch from cleanup to construction; collagen synthesis provides the scaffold and its strength.
| Growth factor | Main role in healing |
|---|---|
| PDGF | Recruits and stimulates fibroblasts and smooth muscle; from platelets and macrophages |
| TGF-β | Fibroblast migration, collagen synthesis, fibrosis; anti-inflammatory |
| VEGF | Angiogenesis — new capillaries in granulation tissue |
| FGF | Angiogenesis and fibroblast proliferation |
| EGF | Epithelial proliferation (re-epithelialization) |
TGF-β is the central driver of fibrosis — in wounds and in chronic diseases such as cirrhosis and pulmonary fibrosis.
Primary vs secondary intention
How a skin wound heals depends on whether its edges can be brought together.
Abnormal healing
Healing fails when the wound environment or the patient cannot support it, and overshoots when collagen deposition is excessive.
| Problem | Features | Examples |
|---|---|---|
| Delayed healing | Persistent inflammation, poor granulation tissue | Infection (most common), diabetes, ischemia, glucocorticoids, malnutrition, vitamin C or zinc deficiency, foreign body |
| Dehiscence | Wound reopens | Mechanical stress (vomiting, coughing) on an abdominal incision |
| Hypertrophic scar | Excess, parallel collagen within wound borders; often regresses | Burns, wounds across tension lines |
| Keloid | Disorganized excess type I and III collagen beyond the borders; does not regress, recurs after excision | Earlobes, chest, shoulders; more common with darker skin |
| Contracture | Excessive wound contraction deforms the tissue | Burns over joints |
Glucocorticoids impair healing by suppressing inflammation and collagen synthesis.
A 70-year-old man who lives alone and eats only toast and tea has swollen, bleeding gums, perifollicular hemorrhages, corkscrew hairs, and a surgical wound that will not heal. Which step of collagen synthesis is impaired?
- The diet lacks fresh fruit and vegetables, pointing to vitamin C deficiency (scurvy).
- Vitamin C is a cofactor for prolyl and lysyl hydroxylase.
- Without hydroxylation, collagen cannot form stable triple helices and cross-links, so vessel walls and new scar tissue are weak.
Answer. Hydroxylation of proline and lysine residues on procollagen, inside the rough endoplasmic reticulum — vitamin C deficiency (scurvy).