Learning Objective
Describe the key mediators and phases of wound healing, including the principal effector cells and clinical correlations.
Wound Healing
Wound healing is a coordinated, multistep process involving inflammation, tissue formation, and remodeling, mediated by growth factors and extracellular matrix–modifying enzymes.
Key Tissue Mediators
| Mediator | Primary Role |
|---|---|
| FGF (Fibroblast growth factor) | Stimulates angiogenesis |
| TGF-β | Promotes angiogenesis and fibrosis |
| VEGF | Stimulates angiogenesis |
| PDGF | Secreted by activated platelets and macrophages; induces vascular remodeling and smooth muscle migration; stimulates fibroblast proliferation and collagen synthesis |
| Metalloproteinases | Extracellular matrix degradation and tissue remodeling |
| EGF | Stimulates cell growth via tyrosine kinase receptors (eg, EGFR/ErbB1) |
Activity
Phases of Wound Healing
Inflammatory Phase (0–3 days after injury)
Effector cells: Platelets, neutrophils, macrophages
Key features:
- Clot formation
- Increased vascular permeability
- Neutrophil migration into tissue
- Macrophages clear debris and orchestrate repair (prominent after ~48 hours)
Proliferative Phase (Days 3 to weeks)
Effector cells:
Fibroblasts, myofibroblasts, endothelial cells, keratinocytes, macrophages
Key features:
- Deposition of granulation tissue
- Synthesis of type III collagen
- Angiogenesis
- Epithelial cell proliferation
- Dissolution of the fibrin clot
- Wound contraction mediated by myofibroblasts
Clinical correlation:
- Vitamin C and copper deficiency → delayed proliferative phase
Activity
Remodeling (Maturation) Phase (1 week to ≥6 months)
Effector cells: Fibroblasts
Key features:
- Replacement of type III collagen with type I collagen
- Increased tensile strength of tissue
- Collagen degradation by collagenases (zinc-dependent metalloproteinases)
Clinical correlation:
- Zinc deficiency → impaired collagen remodeling → delayed wound healing
