Overview

Neutrophil peak≈24–48 h

Macrophage dominanceFrom ≈day 2–3

Scar strength≈10% at 1 week; max ≈70–80% at ≈3 months

1. Haemostasis (seconds–hours). Injured vessels constrict; platelets adhere to exposed collagen, aggregate and degranulate, releasing PDGF, TGF-β and other mediators; the coagulation cascade forms a fibrin clot that plugs the wound and serves as a provisional matrix for migrating cells.

2. Inflammation (≈days 1–4). Vasodilation and increased permeability bring neutrophils (peak ≈24–48 h), which kill bacteria and debride. Macrophages (dominant from ≈day 2–3) phagocytose debris and apoptotic neutrophils, then switch to a reparative phenotype that secretes PDGF, TGF-β, VEGF and FGF — they are the indispensable orchestrators of repair.

3. Proliferation (≈day 4 to week 3). Granulation tissue — fibroblasts, new capillary loops (angiogenesis driven by VEGF and hypoxia) and loose extracellular matrix rich in type III collagen, fibronectin and hyaluronan — fills the defect, appearing red and granular. Keratinocytes from the wound margins and surviving hair follicles and sweat ducts migrate under the scab to re-epithelialise the surface. Myofibroblasts (α-smooth-muscle actin) contract the wound edges.

4. Remodelling/maturation (week 3 to 1–2 years). Type III collagen is replaced by type I collagen, which is reorganised and cross-linked by lysyl oxidase (copper-dependent); vessels regress and the scar pales. Tensile strength is ≈10% of normal at 1 week and plateaus at ≈70–80% after about 3 months. Scars lack hair follicles, sweat glands and rete ridges.

Wounds heal by primary intention when clean edges are apposed (surgical incision: minimal granulation, fine scar) or by secondary intention when the gap is left open (abundant granulation tissue, marked contraction, larger scar).

Function

Restore barrier integrity after injury
Prevent infection and blood loss
Restore tensile strength of the tissue

Regulation: Growth factors (PDGF, TGF-β, VEGF, FGF, EGF, KGF), matrix metalloproteinases and their inhibitors; requires oxygen, protein, vitamin C (prolyl and lysyl hydroxylation of collagen), zinc and copper.

Clinical significance

Impaired healing

Local: infection, ischaemia, foreign bodies, venous hypertension, repeated pressure, radiation. Systemic: diabetes mellitus (microangiopathy, neuropathy, impaired neutrophils), glucocorticoids (inhibit inflammation and collagen synthesis), malnutrition, vitamin C deficiency (scurvy — defective collagen hydroxylation, reopening of old wounds), zinc deficiency, smoking, old age.

Hypertrophic scars and keloids

Hypertrophic scars are raised but stay within the original wound boundary and often regress. Keloids extend beyond the wound margins, rarely regress, are more common in darker skin and on the earlobes, sternum and shoulders, and contain thick hyalinised type I and III collagen bundles.

Chronic ulcers

Venous leg ulcers (medial gaiter area, shallow, with lipodermatosclerosis), arterial ulcers (painful, punched-out, distal), neuropathic diabetic foot ulcers (pressure points, painless) and pressure ulcers fail to progress beyond the inflammatory phase.

Test yourself

During the proliferative phase of wound healing, which collagen type predominates in granulation tissue?

Type I
Type II
Type III
Type IV

Answer: Type III

Fibroblasts first lay down type III collagen in granulation tissue; during remodelling it is replaced by stronger, cross-linked type I collagen, though scar strength never exceeds ≈70–80% of normal skin.