PHASE / TOPIC
WHAT HAPPENS
KEY PLAYERS
CLINICAL LINK
Hemostasis & inflammation
day 0–3
Platelet plug and fibrin clot; neutrophils (day 1–2) then macrophages (day 2–3) clear debris.
Platelets release PDGF and TGF-β; macrophages release growth factors
Macrophages are essential — they direct the next phase
Proliferation
day 3 → weeks
Granulation tissue: fibroblasts laying down type III collagen, new capillaries, myofibroblasts; epithelium grows over.
VEGF, FGF (angiogenesis) · PDGF, TGF-β (fibroblasts) · EGF (epithelium)
Moist, red, granular base of an open wound
Remodeling
week 1 → months
Type III collagen replaced by stronger type I; cross-linking ↑ strength.
Matrix metalloproteinases (collagenases, zinc-dependent)
Strength reaches ~70–80% of normal at ~3 months — never 100%
Primary vs secondary intention
wound type
Primary: clean edges brought together (surgical incision). Secondary: open gap fills from the base.
Secondary needs more granulation tissue and myofibroblast contraction
Secondary healing → bigger scar, contracture
Regeneration vs repair
tissue type
Labile and stable tissues regenerate if the ECM framework survives; permanent tissues heal by scar.
Intact reticulin framework is required
Cirrhosis: framework lost → scar; MI → collagen scar
Collagen building blocks
nutrients
Hydroxylation of proline/lysine; cross-linking; remodeling.
Vitamin C (hydroxylases) · copper (lysyl oxidase) · zinc (MMPs)
Scurvy; Menkes disease; zinc deficiency
Hypertrophic scar
too much, contained
Excess, mostly parallel type I collagen confined to the wound.
Often regresses with time
Raised scar that stays within borders
Keloid
too much, spreading
Excess disorganized collagen (types I and III) that grows beyond the wound.
Does not regress; recurs after excision
Earlobes, face, upper trunk; more common with dark skin
Impaired healing
delay, dehiscence
Wound reopens or fails to close.
Infection (most common), diabetes, ischemia, steroids, malnutrition, foreign body
Chronic wound → Marjolin ulcer (SCC)