Figure 3.

Model for the development of bulging keloid scars. Analysis of deep versus superficial keloid fibroblasts in engineered skin grafted to mice suggested that deep fibroblasts contribute to graft thickening, whereas superficial fibroblasts induce a spreading phenotype.⁵⁵ Other studies described the migratory phenotype of keloid keratinocytes.^53,68 Together, these observations contributed to the model illustrated here. Shown at the left is a schematic diagram of a cross-section of skin following a wound. During wound healing and over time, fibroblasts proliferate, migrate, and deposit ECM to form granulation tissue over which keratinocytes migrate to close the wound. For reasons that have yet to be identified, cells in scars that progress to keloids fail to respond to “stop” signals, and proliferation, ECM production, and migration continue unchecked. Continued production of ECM in fibroblasts in the deep dermis contributes to thickening of the lower dermis, while fibroblasts in the upper dermis exhibit a spreading phenotype, causing an increase in area. With increasing time after injury, the combination of deep dermal thickening and superficial spreading results in a bulging phenotype. Figure adapted with permission from Supp et al.⁵⁵ ECM, extracellular matrix. Color images are available online.