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2015|16 Annual Report Fraunhofer IGB

CELL AND TISSUE ENGINEERING The focus of the Department of Cell and Tissue Engineering is the development of functional in vitro 3D tissue models from isolated primary human cells and pluripotent stem cells under GLP (Good Laboratory Practice) or GMP (Good Manufacturing Practice) guidelines for applications in regenerative medicine, tissue engineering, medical device development and cell-based assays for biocompatibility and stem cell differentiation tests. We develop synthetic, natural and hybrid biomaterials for the maintenance and differentiation of pluripotent (human em- bryonic stem (ES) and induced-pluripotent stem (iPS) cells) and adult stem cells. We further design biofunctionalized nano- or micro-structured material surfaces for the isolation of pure cell cultures from human tissues, particularly adult stem cells. The physiological culture of 3D tissue models is achieved with specially developed computer-controlled bioreactor systems which mimic the biomechanical environment of a specific organ or tissue. The sterility and quality control for cell-based transplants is a complex process, which typically requires multiple transplants for testing. Therefore, we have established non-invasive test methods, Raman microspectroscopy and multiphoton micros- copy, for the pre-implantation analysis of tissue-engineered constructs, which drastically reduces production and quality assurance cost, while increasing the safety of the transplanted constructs. We have developed a two-layer 3D human skin equivalent that has been patented (EP 1 290 145B1). The skin model can be extended to include cell types, such as melanocytes or tumor cells. Furthermore, the skin model is a cost-effective human-based pre-animal test system for penetration and distribution tests of chemicals. Further questions in regard to cell differentiation and death, as well as tumor development and metastasis, can be studied with our model. Additionally, we are developing methods for the creation of cardiovascular implants, regenerative therapies and in vitro 3D test systems. Due to the lack of regenerative potential in the adult cardiovascular system, we primarily work with human ES and iPS cells, as well as complex bioreactor systems. We study our engineered systems in vivo in established small and large pre-clinical animal models in close collaboration with the Department of Medicine/Cardiology at the University of California Los Angeles, where we also have access to human GMP-iPS cell lines. In collaboration with the Department of Women’s Health at the University Hospital of the Eberhard Karls University Tübin- gen we establish novel biofunctional implants, regenerative therapies, medical devices and in vitro 3D test systems in the fields of women s health and rare diseases Competences Isolation and culture of primary cells from different tissues and species in accordance with current GLP or GMP regu- lations ¡ Skin and skin tumors, as well as cardiovascular and uro- genital tissues Biomaterials design ¡ Nano- or micro-structured material surfaces ¡ Synthetic materials ¡ Tissue-specific human recombinant e tracellular matri proteins ¡ Biofunctionalized hybrid approaches 4 6 COMPETENCES that has been patented (EP 1290 145B1). The skin model can 46

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