Epidermal participation in post-burn hypertrophic scar development

The reconstruction of epidermal architecture over time in normotrophic and hypertrophic scars in untransplanted, spontaneously healed partial-thicknes s burns has scarcely been studied, unlike the regeneration of epidermal gra fts used to cover burn wounds and the regeneration of the dermis during hyp ertrophic scarring. The expression of markers of epidermal proliferation, d ifferentiation and activation in normotrophic and hypertrophic scars in spo ntaneously healed partial-thickness burns was assessed and compared with th e expression of these markers in normal control skin of healthy persons to determine whether hypertrophic scarring is associated with abnormalities in the phenotype of keratinocytes. Punch biopsies were taken both of partial- thickness burns after re-epithelialisation and of matched unburned skin. At 4 and 7 months post-burn, biopsies were taken of normotrophic and hypertro phic scars that had developed in these wounds. The biopsies were analysed u sing immunostaining for markers of keratinocyte proliferation, differentiat ion and activation (keratins 5, 10, 16 and 17, filaggrin, transglutaminase and CD36). We observed a higher expression of markers for proliferation, di fferentiation and activation in the epidermis of scars at 1 month post-burn than in normal control skin of healthy persons. There was a striking diffe rence between normotrophic and hypertrophic scars at 4 months post-burn. Ke ratinocytes in hypertrophic scars displayed a higher level of proliferation , differentiation and activation than did normotrophic scars. At 7 months p ost-burn all keratinocyte proliferation and differentiation markers showed normal expression, but the activation marker CD36 remained upregulated in b oth normotrophic and hypertrophic scars. Surprisingly, in matched unburned skin of burn patients, a state of hyperactivation was observed at 1 month. Our results suggest that keratinocytes may be involved in the pathogenesis of hypertrophic scarring.