A 43-year-old man comes to the clinic for evaluation of a healed forehead laceration. Six weeks prior, the patient sustained the laceration when he slipped on an icy sidewalk and struck his forehead against a mailbox. The laceration was promptly irrigated and repaired in the emergency department and has since healed without complication. The patient is concerned about the appearance of the scar; he feels it "stands out" when he gives public presentations for his job. On examination, the scar is pink, firm, and mildly raised, without surrounding erythema or edema; it does not extend beyond the initial wound borders. The patient is reassured that the scar should flatten over the following months. The process by which this occurs relies mostly on enhanced cellular production of which of the following?
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Acute wounds, such as this patient's repaired laceration, transition through an organized wound-healing process to restore tissue continuity and tensile strength. This occurs in 4 phases: hemostasis, inflammation, proliferation, and remodeling. Six weeks after primary repair, this patient's intact, healed wound is most likely undergoing remodeling (also called maturation), the final phase of wound healing that occurs between approximately 3 weeks and 2 years.
Matrix metalloproteinases (MMPs) play a pivotal role in the wound-remodeling phase. Secreted by several different cell types (eg, fibroblasts, macrophages, neutrophils, some epithelial cells), MMPs facilitate the degradation of collagen and other proteins in the extracellular matrix in a highly regulated fashion. This occurs so that type III collagen laid down in a rapid, disorganized manner during the proliferation phase can be replaced by type I collagen, now arranged in well-organized, parallel bundles with extensive cross-linking. The result is both increased tensile strength and decreased thickness (ie, flattening) of the scar.
(Choice B) Plasminogen activators (eg, tissue plasminogen activator released by damaged endothelium) catalyze the activation of plasmin, an important enzyme in the fibrinolytic pathway. Fibrinolysis occurs concomitantly with activation of the coagulation cascade to help control clot propagation; however, this happens immediately after tissue injury during the hemostasis phase.
(Choices C and D) Reactive oxygen species are part of the oxidative burst by which phagocytic cells such as neutrophils destroy engulfed pathogens during the inflammation phase of wound healing. During this phase, neutrophils, as well as macrophages, produce tissue necrosis factor-alpha, a proinflammatory cytokine that leads to increased vascular permeability and further immune cell recruitment. There is often moderate edema, redness, and/or warmth of the wound during this phase.
(Choice E) Vascular endothelial growth factor stimulates endothelial cell proliferation, migration, and differentiation, leading to the formation of new capillaries (ie, angiogenesis). Angiogenesis occurs predominantly during the proliferative phase of wound healing; the resulting increased blood flow often causes the healing wound to be pink and slightly warm.
Educational objective:
During the remodeling phase of wound healing, matrix metalloproteinases facilitate the degradation of collagen and other proteins in the extracellular matrix, causing the replacement of type III, disorganized collagen with type I, well-organized, and cross-linked collagen. This leads to both increased tensile strength and flattening of the scar.