TY - JOUR U1 - Zeitschriftenartikel, wissenschaftlich - begutachtet (reviewed) A1 - Schmidt, Freia A1 - Nowakowski, Sophia A1 - Kluger, Petra T1 - Improvement of a three-layered in vitro skin model for topical application of irritating substances JF - Frontiers in Bioengineering and Biotechnology N2 - In the field of skin tissue engineering, the development of physiologically relevant in vitro skin models comprising all skin layers, namely epidermis, dermis, and subcutis, is a great challenge. Increasing regulatory requirements and the ban on animal experiments for substance testing demand the development of reliable and in vivo-like test systems, which enable high-throughput screening of substances. However, the reproducibility and applicability of in vitro testing has so far been insufficient due to fibroblast-mediated contraction. To overcome this pitfall, an advanced 3-layered skin model was developed. While the epidermis of standard skin models showed an 80% contraction, the initial epidermal area of our advanced skin models was maintained. The improved barrier function of the advanced models was quantified by an indirect barrier function test and a permeability assay. Histochemical and immunofluorescence staining of the advanced model showed well-defined epidermal layers, a dermal part with distributed human dermal fibroblasts and a subcutis with round-shaped adipocytes. The successful response of these advanced 3-layered models for skin irritation testing demonstrated the suitability as an in vitro model for these clinical tests: only the advanced model classified irritative and non-irritative substances correctly. These results indicate that the advanced set up of the 3-layered in vitro skin model maintains skin barrier function and therefore makes them more suitable for irritation testing. Y1 - 2020 UN - https://nbn-resolving.org/urn:nbn:de:bsz:rt2-opus4-29114 SN - 2296-4185 SS - 2296-4185 U6 - https://doi.org/10.3389/fbioe.2020.00388 DO - https://doi.org/10.3389/fbioe.2020.00388 VL - 8 SP - 1 EP - 11 S1 - 11 PB - Frontiers Media CY - Lausanne ER -