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ePaper created 2017-03-14, 10:25:37 | version 1.49.03
HEALTH simple model advanced models with increasing complexity irritation / corrosion phototoxicity l e d o m s i m r e d i p e s s e n k c i h t l l u f l e d o m pigmented squamous cell carcinoma model sun protection melanogenesis with subcutis early stage late stage early stage late stage keratinocytes i broblasts ibroblasts melanocytes melanocytes adipocytes adipocytes SCC cell line 1 SKIN MODELS OF VARYING COMPLEXITY FOR R&D AND PRE-CLINICAL STUDIES Siby ll e T hu d e, K ir s t in L inke, P et ra K lu g e r 3D tissue models for substance testing The Department of Cell and Tissue Engineering is specialized in constructing human three-dimensional tissues. The 3D nature of the scaffolds considerably affects parameters such as metabolic activity, viability, division, morphology and differ- entiation status and thus, ultimately, the function of the tissue as a test model. After many years of development Fraunhofer IGB has established several 3D human skin equivalents of varying complexity. Depending on integrated cells, complexity increases and therefore different aspects of substance testing in healthy or diseased models can help the development of new therapeutic strategies. Epidermis and full thickness skin models as a basis The simple, well stratii ed epidermis model and the full thick- ness skin model with matrix embedded i broblasts are well established in vitro skin models which enable the evaluation of biological responses to substances and their formulations. A variety of applications regarding safety and risk assessment, investigations of cell-cell and cell-matrix interactions or differ- entiation behavior can be performed. Test procedures for the quantii cation of cytotoxic or phototoxic effects of topically or systemically applied substances have been accredited to support customers in their development of medical devices, cosmetics and dermopharmaceutical products [1, 2]. high radiation dose. Therefore the cosmetic industry focuses not only on the improvement of sunscreens, but also on the development of melanogenic substances, which stimulate melanin production in the skin functioning as a self-protective UV-shield. In addition, anti-oxidative substances are used as radical scavengers to prevent light-induced skin damages and even skin cancer. Melanocytes are located in hair follicles as well as in the basal layer of the epidermis and serve a protective function in the skin. When exposed to sunlight they synthesize an important UV-absorbing pigment named melanin. This is then distrib- uted to keratinocytes located in the surrounding area of the melanocytes, thus protecting the DNA from UV-light associ- ated damages. By integrating melanocytes into our in vitro skin models (epidermal or full thickness skin model), Fraunhofer IGB can investigate UV-light associated skin damage, analyze sun protective substances and formulations for their melanogenic or anti-oxidative potential. In addition, we can quantify the tanning and whitening effects of solutions after a dei ned UV-irradiation (UV-A / UV-B or combination) as well as monitor alterations in collagen or elastic i bers caused by aging [3]. In vitro model for human squamous cell carcinoma – Pigmented in vitro skin model for the investigation of light-induced skin damage Sunlight has various effects on human health. Several im- portant metabolic processes are only triggered by sunlight. Longtime sun bathing and extended outdoor activities can cause skin irritation, inl ammation or even skin cancer due to a complex diseased model More than 300,000 new cases of non-melanoma skin cancer (basal cell carcinoma and squamous cell carcinoma) are diagnosed in Germany per year. This increasing number is due to prolonged sun bathing, extended outdoor activities and general exposure to sunlight. Non-melanoma skin cancer 5 2