Collagen accumulation, scar remodeling, and matrix degradation
THE CONTEXT
Scar maturation reflects the balance between extracellular matrix (ECM) synthesis and degradation. Remodeling strengthens the wound while reducing scar size.
Effects of transforming growth factor-b
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Transforming growth factor-b (TGF-b) decreases ECM degradation by inhibiting metalloproteinases.
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TGF-b contributes to scar formation after injury and fibrosis of the lung, liver, and kidneys following chronic inflammation.
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It also limits and terminates inflammation by inhibiting lymphocyte proliferation and the functional activity of other leukocytes.
Collagen synthesis and recovery of strength
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As healing progresses, fibroblasts adopt a more synthetic phenotype and increase ECM deposition. Collagen synthesis strengthens the healing wound.
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Fibroblast collagen synthesis begins on days 3 to 5 and continues for several weeks, depending on wound size.
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Net collagen accumulation depends on both increased synthesis and diminished degradation.
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Remodeling increases scar strength through collagen crosslinking and increased collagen fiber size. Early type III collagen is replaced by more resilient type I collagen.
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Well-sutured skin wounds may recover 70% to 80% of normal skin strength by 3 months.
Matrix metalloproteinases and their inhibitors
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Matrix metalloproteinases (MMPs) contribute to scar shrinkage and require metal ions, such as zinc, for activity.
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MMP-producing cells include fibroblasts, macrophages, neutrophils, synovial cells, and some epithelial cells. Growth factors, cytokines, and other agents regulate their synthesis and secretion.
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Interstitial collagenases cleave fibrillar collagen; the passage lists MMP-1, MMP-2, and MMP-3 in this group.
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Gelatinases, MMP-2 and MMP-9, degrade amorphous collagen and fibronectin.
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Stromelysins, MMP-3, MMP-10, and MMP-11, degrade several ECM constituents, including proteoglycans, laminin, fibronectin, and amorphous collagen.
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Tissue inhibitors of metalloproteinases (TIMPs), produced by most mesenchymal cells, inhibit MMPs. The balance between MMP and TIMP activity determines the ultimate size and composition of the scar.