Scar Re-pigmentation: Melanocyte Repopulation In Temporal Human Skin Scarring And Its Ongoing Interaction With Inflammation And Angiogenesis
Sara Ud-Din1, Philip Foden2, Mohsin Mazhari2, Samer Al-Habba2, Mohamed Baguneid2, Ardeshir Bayat1.
1University of Manchester, Manchester, United Kingdom, 2Manchester University NHS Foundation Trust, Manchester, United Kingdom.
BACKGROUND The relationship between inflammation and skin pigmentation remains ill-understood. Inflammation in scars affect re-pigmentation. The mechanisms behind this remain unclear, but immune-modulatory function of melanocytes, may provoke an inflammatory response in wound healing. METHODS The aim here was to investigate re-pigmentation of skin scarring created in 62 human subjects with similar skin-types over an 8-week period (8W) using a skin-biopsy model. Objective devices, which quantified melanin (SIAscopy), erythema (colorimeter), blood-flow (full-field laser perfusion imaging (FLPI), dynamic-optical coherence tomography (D-OCT) were used to monitor wounds/scars weekly and this was supported by detailed gene and protein analysis. RESULTS SIAscopy and colorimeter showed a significant increase from normal skin (NS) to W1 (18.8Au to 8.4Au:p=0.004; 30Au to 45.1Au:p<0.001 respectively) with a gradual reduction to W8. Masson Fontana and Melan-A analysis supported this trend (NS-W1:p=0.04, p=0.05; W1-W8:p=0.02, p=0.04 respectively) and the percentage area of epidermis in scar tissue containing melanin remained less than that of surrounding NS as pigment was absent from the centre and gradually crept in from the periphery. Erythema demonstrated the same trend (p<0.001). Blood flow measured by FLPI and D-OCT peaked at W1 (394.9Pu, 0.161Au respectively) (p<0.001) and decreased to W8 (130Pu, 0.107Au respectively) (p<0.001). Inflammation analysis by IL6 and IL10 intensity increased at W1 compared to NS (p=0.04, p=0.03 respectively). CD31 vessel density and VEGFA marker areas increased to W3 (105.7vessels/mm2:p=0.002, 72.9%:p=0.01 respectively) and reduced to W8. Mast-cells tryptase and chymase density increased at W1 compared to NS (44cells/mm2, p=0.002; 41cells/mm2,p=0.04 respectively), and decreased by W8 (26cells/mm2,p=0.003; 20cells/mm2,p=0.01 respectively) reaching a level similar to that observed in NS. CONCLUSIONS Here, we demonstrate, melanocyte repopulation of scars in temporal human skin biopsies and confirm the correlation between re-pigmentation, inflammation and angiogenesis. These findings may lead to better understanding and assessment of re-pigmentation in response to future scar therapies.
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