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Melanocyte Re-population And Cutaneous Re-innervation In Temporal Wound Healing And Scar Formation In Human Skin
Sara Ud-Din1, Philip Foden2, Katie Stocking2, Douglas McGeorge3, Ardeshir Bayat1.
1University of Manchester, Manchester, United Kingdom, 2Manchester University Foundation Trust, Manchester, United Kingdom, 3Nuffield Grosvenor Hospital, Chester, United Kingdom.

Communication between the nervous system and epidermal melanocytes in cutaneous healing remains underexplored. Therefore, the aim here was to quantitatively investigate melanocyte re-population and re-innervation in skin scarring created in human volunteers with similar skin-types over a sequential weekly time period upto eight weeks (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 the scars weekly. Immunohistochemical analysis of melanogenesis, angiogenesis and innervation were performed.

SIAscopy and colorimeter showed a significant increase in melanin from uninjured intact skin (UIS) to W8 (210Au to 235Au:p=0.002; 20Au to 35Au:p=0.003 respectively). Masson Fontana, Melan-A and C-Kit analysis showed a 62% reduction at W1, as melanocytes were only evident at the wound edges and a 28% increase to W8 (p=0.04, p=0.04, p=0.03 respectively). The percentage of melanin in the epidermis of scar tissue remained less than that of surrounding UIS as pigment was absent from the centre and gradually migrated in from the periphery. Innervation analysis by PGP9.5, NGF and SP correlated with melanocyte analysis by showing an increased expression from UIS to W8 (p=0.01, p=0.02, p=0.02 respectively) and found to be greatest expression in the centre of the wound in the dermis but no expression in the basal layer of the epidermis at early time points. Erythema increased to W1 and reduced to W8 (p<0.001). Blood flow peaked at W1 (394.9Pu, 0.161Au respectively) (p<0.001) and decreased to W8 (130Pu, 0.107Au respectively) (p<0.001). CD105 demonstrated the same trend (p<0.02).

We suggest a close relationship between intraepidermal innervation and melanocyte re-population with direct relevance to re-pigmentation post-scarring. These findings enhance our understanding and may lead to the development of objective classification of melanocytic re-population and skin re-innervation in response to scar therapies.

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