Wound Healing and Cytokines- Different overlapping events: inflammatory phase, proliferative phase, and tissue remodeling; some sources cite vascular phase (hemostasis) as first phase (Table 1-6)
| | | | | | | Table 1-6 Stages of Wound Healing | PHASE I: INFLAMATION (first 6–8 h)
Clot information → neutrophil/macrophages debride wound | | |
⇒ Platelets (main player)
Release chemotactic factors (fibrinogen, fibronectin, thrombospondin, vWF, ADP) attracting other platelets, WBCs and fibroblasts; produces fibronectin which acts as provisional matrix for fibroblast migration; also releases PDGF, TGFα, and TGFβ
⇒ Neutrophils
Appears first and in greater numbers than macrophages; attracted by fibrinogen, fibrin split products, leukotrienes, and C5a; important in tissue debridement and bacterial killing
⇒ Macrophages
Becomes predominant leukocyte as process continues; aids in tissue debridement and critical for wound healing as helps transition from inflammation to repair; attracted by fibrin degradation products, fibronectin, fragments of collagen, TGF-β; release growth factors which stimulate fibroblasts and extracellular matrix (ECM) production
| PHASE 2: GRANULATION TISSUE FORMATION (5–7 days but may last longer)
Keratinocyte re-epithelialization + granulation tissue formation + angiogenesis | | |
⇒ Keratinocytes (main player)
Re-epithelialization begins several hours after injury; keratinocytes leapfrog over each other from wound edges and adnexal structures; collagenase produced and aids in migration
⇒ Fibroblasts
Migrates to wound 48 h after injury, move along fibronectin matrix from initial clot; type III collagen in early wound; contraction by myofibroblasts (typically second week of healing)
⇒ Blood vessels
Stimulation of new vessel growth via VEGF, TGF-β, thrombospondin, angiotropin, angiogenin, and SPARC (secreted protein acidic and rich in cysteine)
| PHASE 3: TISSUE REMODELING (after third week)
Granulation tissue become mature scar tissue | | |
⇒ Fibroblasts (main player)
Produces fibronectin, hyaluronic acid, collagen → key role in cell migration/tissue support; fibronectin for cell migration and template for collagen deposition
⇒ Collagen
Granulation tissue initially composed of type III collagen; gradually replaced by type I collagen and scar’s tensile strength increases; final strength only 70–80% preinjured skin
| | | | | | | | | | | | | | | | | | Scar strength: 5% at 1 week, 20% at 3 weeks, 70–80% at 1 year | | | | | | | | |
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