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ePaper created 2013-09-24, 11:56:35 | version 1.25.20
CELL AND TISSUE ENGINEERING The core competence of the Cell and Tissue Engineering De- partment is the development of functional 3D tissue models in vitro from isolated primary human cells. With these tissue models, we help solve complex challenges in the areas of re- generative medicine, tissue engineering and the development of medicinal products and cell-based assays for toxicology. We develop biocompatible micro- and nano-structured material surfaces for the effective isolation and culture of primary cells and for optimal cell type-specific cultivation, in particular of adult stem cells. The physiological cultivation of our 3D tissue models is made possible by computer-controlled bioreactor systems designed specifically for the cell type in question. Ste- rility testing and quality control of cell-based transplants is a laborious process, which always requires two graft samples – one for testing and one for transplantation. We are therefore establishing a non-invasive reference method based on Raman spectroscopy. A two-layered human 3D skin equivalent has been patented (EP 1 290 145B1) and accredited for the testing of the bio- compatibility of medicinal devices (DIN ISO 10993-5). The skin model can be extended by further cell types such as mel- anocytes or tumor cells. It is also suitable – as a preliminary stage to animal testing – in investigations of the penetration and the distribution of test substances, as required by the EU chemicals regulation REACH. The model’s scope extends to investigation of differentiation, apoptosis, and also of tumor initiation and graduation. We have recently succeeded in inte- grating vascular structures (blood vessel equivalents) into the skin model. In addition, we were able to automate the com- plete process for manufacturing the avascular skin models. A further focus is the miniaturization and the characterization of our 3D intestinal testing system. Our accredited two-di- mensional intestinal assay based on colon carcinoma cells (2D Caco-2 model) allows validated permeability and transport studies of potential candidate drugs and other substances at the intestinal barrier. We have also been able to establish GMP conditions for the cultivation of our vascularized matrix (Bio- VaSc) in specific bioreactors. This matrix is used to generate complex organ structures. As part of a project funded by the German Federal Ministry of Education and Research (BMBF) we are currently preparing the first clinical study of a trachea transplant based on the BioVaSc. Isolation and culture of primary cells from different tissues and species according to GLP or GMP regulations Micro- or nanostructured (bio)material surfaces Skin including skin tumor, liver, intestine, trachea, car- diovascular tissue Establishing processes to develop three-dimensional or- ganotypical cell cultures as testing model or for tissue re- construction BioVaSc (biological vascularized scaffold) Tissue-specific computer-controlled bioreactors Vascularized human liver, intestine and trachea model Establishing methods for non-destructive cell and tissue characterization by means of Raman spectroscopy With the help of these vascularized human test systems, the absorption, distribution, metabolism, excretion and toxicity (ADMET) of substances or medicinal products can be inves- tigated. These parameters are critical in the characterization of the pharmacokinetic and toxicological properties of active substances. Our findings can be extrapolated directly to the COMPETENCES 50