Tissue engineered human scar models identify extracellular matrix and in!ammatory cytokine di"erences between normotrophic, hypertrophic and keloid scars

Hypertrophic and keloid scars are the result of unknown abnormalities in the wound healing process. The aim of this study was to develop physiologically relevant, human in vitro abnormal scar models for hypertrophic and keloid scars and compare these to normotrophic scars and normal skin to identify dierences in the pathogenesis of different scars. Keratinocytes and broblasts from normal skin and scars (normotrophic, hypertrophic, keloid) were used to construct skin equivalents (SE). All SE showed normal epidermal dierentiation and proliferation. Both abnormal scars showed increased contraction, dermal thickness and myobroblasts (αSMA) compared to normal skin and normotrophic scar. Notably, the expression of extracellular matrix associated genes showed dierential proles between abnormal scars and normal skin (HGF, HAS1, COL4A2, MMP3) and between the two abnormal scars (IL-18, CCL5, MMP1, ITGA5). Also inammatory cytokine secretion (CCL5, CXCL1, IL-6, IL-18) was lower in hypertrophic scar compared to normotrophic or keloid scars. Using tissue-engineered scar models we have identied parameters which distinguish normal skin and normotrophic scars from abnormal scars, and hypertrophic scars from keloids.