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ePaper created 2016-03-17, 15:06:18 | version 1.45.01
6 4 DEVELOPMENT OF A FUNCTIONAL THREE-LAYER FULL-SKIN MODEL Birgit Huber, Kirsten Borchers, Petra J. Kluger Functional skin for transplants Patients with extensive burns, open diabetic foot wounds or skin loss due to tumor removal require aesthetic and func- tional skin replacements. When transplanting a patient’s own skin is not possible, there are a number of different skin sub- stitutes on the market that can replace the top two layers of skin, the dermis and the epidermis. However, if the underlying fat tissue is affected, the current products on the market are inadequate. Therefore, tissue models that include the underly- ing fatty tissue are urgently needed. Researchers now focus on the production of three-layer full-skin models that have the typical appearance and performance of native skin. As part of the EU project “ArtiVasc 3D”, Fraunhofer IGB is establishing methods for the construction and characterization of a three- layer full-skin model. Culture of mature adipocytes Stem cell derived adipocytes are the gold standard for the production of fat cells. The differentiation process is time consuming and costly. The use of already matured adipocytes has received little attention because they are prone to dedif- ferentiation when cultured. Approximately 50 percent of adiposed tissue consists of mature adipocytes. Thus they can be abundantly isolated from small amounts of tissue and can be immediately used in a full-thickness skin model. As the body’s own cells are not immunogenic and adipocytes have a slow renewal rate of only about 5 percent per year, they may be an interesting cell source for long-term full-skin implants. At Fraunhofer IGB, we have established a culture medium that slows the dedifferentiation of mature adipocytes, enabling their use in the construction of full-thickness skin models [1, 2, 3]. Construction and culturing three-layer skin models Mature adipocytes are integrated into a collagen type I hy- drogel (Fig. 1) to create an adipose layer. A dermal layer made of a collagen type I hydrogel and fibroblasts is placed on top of the model. Finally, a multilayered keratinocyte-containing epidermis with the typical cornified layer is added, resulting in three-dimensional full-skin model (Fig. 2). A suitable culture medium is available at IGB for maintaining the functionality of the mature adipocytes for up to 14 days in the skin model and in parallel allowing the keratinocytes to differentiate and form a multilayer keratinized epidermis (Fig. 3). Therapeutic future: Vascularized full-skin models For the large-scale replacement of full-thickness skin, the proper vascular structures within the skin must be included to transport oxygen and nutrients to the cells. To enable such structures, co-cultures have been developed to integrate vascular cells such as endothelial cells into the mixture of adipocytes, fibroblasts and keratinocytes in the skin model An optimized medium for the culture of all four cell types is now available at Fraunhofer IGB. In the future, the establish- ment of a full-skin model should be supplemented with blood vessel-like structures through which the nutrient and oxygen exchange can take place. The development of 3D tissue models is an important stepping-stone in the future of reconstructive medicine. Fraunhofer IGB continues to contribute to this future by devel- oping patient-specific implants to replace functionless tissue MEDICINE 1 200 μm 64 1200 μm