Skin healing

(A) In any wound, the initial gap is filled by blood that, upon clotting (formation of fibrin polymers), provides the initial stability to the wound. Plasma fibronectin, present in the clot, can be cross-linked with extracellular matrix components and fibrin to bridge the clot and tissues.
(B) The epidermal cells at the edges of the wound lose contact with other epithelial cells and with their basement membranes. At the same time, this loss of contact probably acts as a signal to trigger migration of the cells. Concurrently, basal epidermal cells adjacent to the migrating cells undergo division. The result of this coordinated migration and cell division is the gradual covering of the epidermal defect. The breakdown products from the injured cells, fibronectin, and lysosomal enzymes from leukocytes act as chemoattractants, resulting in an influx of macrophages, myofibroblasts, and fibroblasts. Simultaneously, endothelial cells proliferate and neovascularization begins. The phagocytic cells attracted to the wound remove part of the clot, while fibroblasts and myofibroblasts begin to deposit a new extracellular matrix.
(C) The concentric migration of epidermal cells, sustained by the mitotic activity of the trailing cells, fills the wound gap and displaces the remnants of the original clot (scab) toward the surface. Contact with other epidermal cells is the signal that stops migration. The trailing cells not only divide but also secrete basement membrane components. In this manner, the continuity of the epidermal basement membrane is restored. In a similar fashion, the concerted activity of fibroblasts, myofibroblasts, macrophages, and endothelial cells fills the dermal gap. At this point, the number of macrophages and myofibroblasts declines. Those capillaries that failed to establish a definitive flow pattern begin to be obliterated, and accumulation of the definitive extracellular matrix is initiated.
(D) The gap created by the wound has been repaired. The mitotic activity of the epidermal cells will restore the epidermal thickness. Most capillaries of the initial granulation tissue have been reabsorbed, and the dermal gap has been filled with a dense, almost avascular, extracellular matrix, composed predominantly of type I collagen.