ABSTRACT
UNLABELLED: Increasing data suggest that the skin nerve system is involved in wound healing. The objective of this study was to investigate the outgrowth of nerve fibers during the burn wound remodeling process and to analyze possible differences between normotrophic and hypertrophic burn wounds. In a prospective study, biopsies were taken from 22 patients with spontaneously healed partial-thickness burns at 1, 4 and 7-month post-burn. Nerve outgrowth and the expression of the neuropeptides substance P, neurokinin A, calcitonin gene-related peptide, vasoactive intestinal peptide and neuropeptide Y was monitored using immunohistochemistry. Our results showed that the number of nerve fibers gradually increased in both the dermis and the epidermis, but that they did not reach the levels of expression present in matched unburned skin of the same patient. A significantly higher number of nerve fibers were observed in normotrophic scars compared with hypertrophic scars. The number of neuropeptides-containing nerves in normotrophic and hypertrophic scars were similar. IN CONCLUSION: 7 months after wound closure, burn wound scars contain less nerve fibers than unburned skin. The significantly higher number of nerve fibers in normotrophic, compared with hypertrophic scars suggests a regulatory role for the skin nerve system in the outcome of burn wound healing.
Subject(s)
Burns/physiopathology , Calcitonin Gene-Related Peptide/analysis , Cicatrix, Hypertrophic/physiopathology , Nerve Growth Factors/analysis , Neurokinin A/analysis , Wound Healing , Adult , Aged , Biomarkers/analysis , Burns/metabolism , Cicatrix/physiopathology , Cicatrix, Hypertrophic/metabolism , Follow-Up Studies , Gene Expression Regulation , Humans , Middle Aged , Prospective Studies , Skin/chemistry , Skin/physiopathologyABSTRACT
The reconstruction of epidermal architecture over time in normotrophic and hypertrophic scars in untransplanted, spontaneously healed partial-thickness burns has scarcely been studied, unlike the regeneration of epidermal grafts used to cover burn wounds and the regeneration of the dermis during hypertrophic scarring. The expression of markers of epidermal proliferation, differentiation and activation in normotrophic and hypertrophic scars in spontaneously healed partial-thickness burns was assessed and compared with the 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 hypertrophic scars that had developed in these wounds. The biopsies were analysed using immunostaining for markers of keratinocyte proliferation, differentiation and activation (keratins 5, 10, 16 and 17, filaggrin, transglutaminase and CD36). We observed a higher expression of markers for proliferation, differentiation and activation in the epidermis of scars at 1 month post-burn than in normal control skin of healthy persons. There was a striking difference between normotrophic and hypertrophic scars at 4 months post-burn. Keratinocytes in hypertrophic scars displayed a higher level of proliferation, differentiation and activation than did normotrophic scars. At 7 months post-burn all keratinocyte proliferation and differentiation markers showed normal expression, but the activation marker CD36 remained upregulated in both 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.
