Induction of angiogenic and inflammation-associated dermal biomarkers following acute UVB exposure on bio-engineered pigmented dermo-epidermal skin substitutes in vivo
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.
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 5 weeks onto full-thickness skin wounds on the back of immuno-incompetent rats, exposed to a single UVB dose of 250 mJ/cm2 or unexposed and excised after 1 week. 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.
We observed a significantly enhanced ingrowth rate of blood capillaries, but not of lymphatic capillaries at 1 week 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.
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.
KeywordsAcute UVB Human skin substitute Tissue engineering Blood- and lymph-angiogenesis Inflammatory response Granulocyte infiltration Monocyte/macrophage recruitment HIF-1α expression
This work was financially supported by the Clinical Research Priority Programs (CRPP) of the Faculty of Medicine of the University of Zurich. We are particularly grateful to the Gaydoul Foundation and the sponsors of “DonaTissue” (Thérèse Meier and Robert Zingg) for their generous financial support and interest in our work.
Compliance with ethical standards
Conflict of interest
ER and MM are co-founding members and shareholders of “Cutiss AG”, a company to fund the further development of the tissue-engineered skin substitutes. All other authors declare that they have no conflict of interest.
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