With a reduction in inflammatory stimuli and therefore in the number of inflammatory mediators, the wound milieu is altered to allow new tissue formation. The wound enters the fibroplastic phase, which is usually established within 5 days of wounding and lasts for up to 4 weeks.
The macrophage, so critical to the inflammatory stage of wound healing, is also essential to new tissue development through macrophage-derived growth factors (MDGF),. The MDGF list is long (though not as long as the list of Lincoln bedroom visitors) and includes platelet-derived growth factor (PDGF), transforming growth factor-alpha (TGF-a), transforming growth factor beta (TGF-b), interleukin-1 (IL-1), and tumor necrosis factor (TNF).

fibroblast migrationTo produce new tissue, fibroblasts proliferate in the wound and migrate with the help of the growth factors and a very important glycoprotein called fibronectin. Fibronectin acts as a conduit for fibroblasts. It binds to both the wound matrix and the fibroblast, allowing the fibroblast to march down it (the fibronectin), move along the chemotactic gradient of growth factors, and take up residence in the wound (image expandable to 27K JPEG).

collagen depositionOnce in the wound fibroblasts begin to synthesize collagen fibers and produce proteoglycans, structural proteins, and adhesive proteins -- connective tissue ground substances. Vitamin C, iron, and copper are essential to the synthesis of collagen, which constitutes 50% of the protein found in scar tissue. Other fibrous protein in the wound include elastin and reticulin (click on image to download 1.1 meg Quicktime animation).

vascular buddingCollagen, however, cannot be synthesized in the absence of adequate oxygen supply. But the wound has derailed blood flow. Angiogenesis is required. Through their enzymatic actions, growth factors break down the vascular membrane of the venules. Endothelial cells that migrate through the defect aggregate to form vascular buds (click on image to download a 98K Quicktime movie).

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