Clinical meaning
Wound healing is a complex, overlapping biological process that occurs in four distinct but interrelated phases: hemostasis, inflammation, proliferation, and maturation (remodeling). Hemostasis begins immediately upon tissue injury and lasts approximately 5 to 10 minutes. When a blood vessel is damaged, vasoconstriction occurs as the first response to reduce blood loss. Platelets adhere to exposed collagen in the vessel wall, aggregate together, and form a platelet plug. The coagulation cascade is activated, converting fibrinogen to fibrin, which stabilizes the platelet plug into a clot. This clot serves as a temporary matrix for cell migration in subsequent phases. The inflammatory phase begins within hours of injury and typically lasts 1 to 6 days. Neutrophils are the first white blood cells to arrive at the wound site (within 6 to 8 hours), where they phagocytize bacteria and debris. Macrophages follow within 24 to 48 hours and are considered the most critical cells in wound healing because they not only continue phagocytosis but also release growth factors (such as platelet-derived growth factor, transforming growth factor-beta, and vascular endothelial growth factor) that recruit fibroblasts and stimulate angiogenesis. Cardinal signs of inflammation include redness (rubor), heat (calor), swelling (tumor), pain (dolor), and loss of function (functio laesa). The proliferative phase spans approximately day 4 through day 21 and involves three key processes: granulation tissue formation, wound contraction, and epithelialization. Fibroblasts migrate into the wound and synthesize collagen, the primary structural protein of the extracellular matrix. New capillaries sprout from existing blood vessels (angiogenesis), creating the characteristic red, granular appearance of healthy granulation tissue. Myofibroblasts contract and pull wound edges closer together. Epithelial cells migrate across the wound surface from the wound margins, a process called epithelialization. The maturation (remodeling) phase begins around day 21 and can continue for up to 2 years. During this phase, type III collagen is gradually replaced by stronger type I collagen through a balance of collagen synthesis and degradation by matrix metalloproteinases. The tensile strength of the wound increases but never exceeds approximately 80% of the original tissue strength. The scar becomes less vascular and transitions from red or purple to a paler color as blood vessels regress. Nutritional status significantly impacts healing: vitamin C is essential for collagen synthesis and immune function; zinc is required for cell division and protein synthesis; iron is necessary for oxygen transport to the wound bed; and adequate protein intake (1.25 to 1.5 g/kg/day for healing wounds) provides the amino acids needed for tissue repair.