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   <subfield code="a">Induction of angiogenic and inflammation-associated dermal biomarkers following acute UVB exposure on bio-engineered pigmented dermo-epidermal skin substitutes in vivo</subfield>
   <subfield code="h">[Elektronische Daten]</subfield>
   <subfield code="c">[Katarzyna Micka-Michalak, Thomas Biedermann, Ernst Reichmann, Martin Meuli, Agnes S Klar]</subfield>
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   <subfield code="a">PURPOSE Ultraviolet (UV) radiation adversely affects skin health at cellular and molecular levels. Hence, UV radiation can directly induce inflammatory responses in the dermis by inducing erythema, edema, inflammation, dermal fibroblasts alterations, and extracellular matrix modifications. METHODS Human keratinocytes, melanocytes, and fibroblasts were isolated from skin biopsies, cultured, and expanded in vitro. Fibroblasts were seeded into collagen type I hydrogels that were subsequently covered by keratinocytes and melanocytes. These pigmented dermo-epidermal skin substitutes (pigmDESS) were transplanted for 5weeks onto full-thickness skin wounds on the back of immuno-incompetent rats, exposed to a single UVB dose of 250mJ/cm or unexposed and excised after 1week. The effects onto the dermis were assessed regarding cell number, cell phenotype, and cell proliferation. Local inflammation by granulocytes (HIS48) or macrophages (CD11b, iNOS) was analyzed by immunohistochemistry staining. RESULTS We observed a significantly enhanced ingrowth rate of blood capillaries, but not of lymphatic capillaries at 1week post-irradiation. Moreover, the enhanced vascularization of pigmDESS after UVB exposure was concomitant with a high infiltration of granulocytes and monocytes/macrophages to the dermal part of grafts. In addition, a heterogeneous expression of HIF-1α and TNFα was detected at this early phase after UVB exposure. In local cellular response examination, results only show a moderate cell proliferation in the dermis. CONCLUSIONS We were able to define early markers of UVB-induced effects in the dermis of pigmDESS. Overall, a single UVB dose induces temporary acute angiogenic and immune responses during the early post-irradiation phase in vivo.</subfield>
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