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BRAIN AG and Mannheim University develop 3D skin models for health care and cosmetics

Research collaboration in project M2Aind for new real-time and high-resolution screening technologies of 3D skin spheroids. Mannheim University of Applied Sciences builds on expertise in 3D cell culture and advanced live cell imaging. BRAIN contributes unique skin reporter cells, screening compound libraries and market knowledge. Review article in Journal of Cellular Biotechnology.

The M2Aind (Multimodal Analytics and Intelligent Sensorics for the Health Industries) research project is a Public-Private-Partnership project led by Mannheim University of Applied Sciences (MUAS, Hochschule Mannheim). M2Aind kicked off in January 2017 and is sponsored by the German Federal Ministry of Education and Research (BMBF). BRAIN has been an active partner of M2Aind from the start. Joint projects of BRAIN and MUAS include the development of a 3D skin model for better understanding of skin physiology with the aim to provide new insights for health care and cosmetic applications.


  • Biosensors are biological detection systems used to identify minute quantities of substances.
  • Biotechnology is the study of all processes involving life cells or enzymes for the transformation and production of certain substances.
  • Pathogenity is the ability to cause a disease. One differentiates between human, animal, and plant pathogens which specifically cause a disease in either humans, animals or plants.
  • Screening is a systematic test procedure that is used to identify certain characteristics within an array of samples or persons. In molecular biology screening is used to filter a designated clone out of a gen bank, for example.
  • Selection in a biological context means the assortment of organisms due to their characteristics. On the one hand, this could be natural selection ("survival of the fittest") like in evolutionary processes. On the other hand, selection by man, e.g. breeding, is called artificial selection. Artificial selection is also used in genetic engineering to identify a genetically modified organism due to its new characteristics (e.g. resistance to antibiotics).
  • Genetic sequences are successions of the bases adenine, thymine, guanine, and cytosine on the DNA (or uracil instead of thymine in the case of RNA).
  • Stem cells are cells from the embryo, fetus or adult that that have the ability to divide for indefinite periods in culture and give rise to specialized cells. In Germany it is illegal to extract the stem cells from embryos.
  • Physiology is the study of the biochemical and physical processes in cells, tissues and organs of creatures.
  • Federal Ministry of Education and Research

Improved 3D spheroid screening

Skin cells grown in 3D spheroids undergo differentiation. Human HaCaT skin cells were cultivated in 3D to form spheroids. 7 days later, they were sliced and stained for markers of basal (CK14, red) and more differentiated epidermal layers (CK10, green). The picture shows a confocal section demonstrating a stratification of cells in the spheroid culture (Image dimension 376 µm). © Mannheim University of Applied Sciences (M2Aind)

Breakthroughs in 3D skin modeling are perceived as potential game changers for various market segments. Current research and development activities for new skin applications are still partly based on 2D cell culture. In such a setting, skin cells are cultivated in one layer in petri dishes before being exposed to selected compounds tested for potential skin applications. Conversely, human skin is organized three-dimensionally which sets quality limits for 2D screening methods. As a consequence, 3D cell culture technologies were developed as early as the 1950s and are successfully used in many laboratories around the world today. The multicellular setting of 3D models allows for a much better interaction of cells with each other and with the extracellular matrix. They are therefore much more representative of the in vivo environment of human skin. Even newer technologies focus on organizing the cells in spherical micro-tissues with the advantage of allowing better standardization and automatization for industrial applications.Current challenges for the broader industrial use of 3D spheroids are rooted in limited methods available to analyze the fast biological processes that take place within the cell. The M2Aind project of MUAS and BRAIN seeks to overcome this limitation by developing new technologies that can visualize the molecular processes that are ongoing in the different skin layers in 3D spheroids in real-time and with high-resolution.

First review article

As a first project milestone, the research partners MUAS and BRAIN have now published a review article entitled “In Vitro Skin Three-Dimensional Models and Their Applications” in the Journal of Cellular Biotechnology. The article describes the composition as well as principal features and functions of human skin. It discusses the setup, prerequisites, advantages, and disadvantages of currently available in vitro 3D skin models and compares them in a comprehensive overview table. The key advantages of the new approach within the M2Aind projects are a more realistic understanding of the physiological behavior of skin cells and the discovery of superior small-molecule actives.

Potential future applications

Within M2Aind, researchers from MUAS are building on their special knowledge and infrastructure for 3D cell culture and analytics. Dr Rüdiger Rudolf, Professor of Biosensorics at MUAS and coordinator of the M2Aind impulse project M2OGA, says: “The review article also gives an outlook on prospective future developments, including the use and exploitation of novel human stem cell technologies for personalized diagnosis, therapy development, and regenerative medicine. The review serves as a guide for choosing appropriate cell models in skin pharmaceutical and cosmetics research and has helped the cooperation partners BRAIN and MUAS in further shaping common goals.”BRAIN has developed special expertise for engineering reporter cells in human skin for industrial applications. This knowledge plus knowledge of market-relevant application fields is now being transferred into M2Aind. Dr Torsten Ertongur-Fauth, Research Scientist & Project Manager at BRAIN, says: “3D spheroid models of the skin are great tools to understand how skin cells are coping with detrimental environmental influences, for example mechanical stress, UV radiation or pathogens. However, it is still challenging to visualize the molecular processes that are ongoing in the different keratinocyte layers in real-time and with high-resolution. So, we are very pleased to have the support of our partner MUAS to further develop our unique skin reporter cells into advanced 3D models that allow industrial screenings for new small-molecule actives.”The timeframe for M2Aind is four years with the potential for additional four years upon positive mid-term evaluation. Currently 37 partners from industry and research are involved. The BMBF funding for the first four years period has been approved for EUR 6 Mio.

Further information

Journal of Cellular Biotechnology 3 (2017) 21-39: In Vitro Skin Three-Dimensional Models and Their Applications, DOI 10.3233/JCB-179004, IOS Press.

Website address: https://www.gesundheitsindustrie-bw.de/en/article/press-release/brain-ag-and-mannheim-university-develop-3d-skin-models-for-health-care-and-cosmetics/