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Wound healing progresses through hemostasis, inflammation (neutrophil and macrophage recruitment), proliferation (fibroblast collagen deposition and angiogenesis), and remodeling (collagen maturation). Growth factors (VEGF, FGF, PDGF, TGF-β) released during each phase recruit and activate specific cell types. The transition between phases is tightly regulated; disruption by infection, hypoxia, or malnutrition impairs healing and promotes chronic wounds or excessive scarring.
From your study of tissue histology, you know that tissues are organized collectives of specialized cells embedded in extracellular matrix — and that disrupting this organization (a wound) demands a coordinated repair response. Wound healing is not a single event but a sequence of four overlapping phases, each with distinct cellular players and molecular signals. Understanding the sequence as a relay race — where each team hands off to the next — is the key mental model.
The first phase, hemostasis, begins within seconds. Damaged blood vessels trigger platelet aggregation and the coagulation cascade, forming a fibrin clot that plugs the breach and stops bleeding. This clot is not just a plug; it is a scaffold and a signal depot. Platelets degranulate, releasing PDGF (platelet-derived growth factor) and TGF-β, which recruit the next phase's cellular workforce. Without successful hemostasis, the wound environment is too chaotic for repair to begin.
The second phase, inflammation, dominates the first few days. Neutrophils arrive first (within hours), clearing debris and fighting bacteria through phagocytosis and oxidative burst. They are short-lived; macrophages arrive next and take over as the conductors of repair. Macrophages do three things: they continue debris clearance, they release pro-inflammatory cytokines (IL-1, TNF-α) that amplify the immune response, and crucially, they shift phenotype and begin releasing VEGF (vascular endothelial growth factor) and FGF (fibroblast growth factor) to initiate the next phase. This macrophage "switch" from inflammatory to reparative behavior is a pivotal transition point — if it fails, inflammation becomes chronic.
The third phase, proliferation, rebuilds the tissue scaffold. Fibroblasts, recruited by PDGF and TGF-β, migrate into the wound and deposit collagen (initially type III, the emergency scaffold). Simultaneously, VEGF drives angiogenesis — sprouting of new capillaries into the wound to supply the metabolically active repair tissue. The combination of fibroblasts, collagen, and new vessels forms granulation tissue, a provisional matrix that fills the wound bed. Epithelial cells at the wound margins also migrate inward to re-cover the surface. The provisional matrix is strong enough to hold tissue together but not yet optimized for load-bearing.
The final phase, remodeling, can last months to years. Type III collagen is replaced by the stronger type I collagen, cross-linking increases, and the matrix is reorganized along lines of mechanical stress. Mature scar tissue reaches roughly 70–80% of original skin strength — never quite 100%. This limitation is because repair replaces damaged tissue with scar rather than regenerating the original architecture. Disruptions at any phase — infection that extends inflammation, hypoxia that prevents angiogenesis, malnutrition that limits collagen synthesis — stall the relay handoff. The result is a chronic wound stuck in one phase, or excessive scarring (keloids, hypertrophic scars) from unresolved fibroblast activity. Recognizing which phase has stalled is the clinical basis for wound management.