Cell and Tissue Engineering
Fraunhofer Institute for Interfacial Engineering and Biotechnology
- Tissue engineered fat test model
The focus of Cell and Tissue Engineering Department is the development of functional in vitro 3D tissue models from isolated primary human 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 toxicology. We develop biomaterials and biofunctionalized micro- or nano-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 PC-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 spectroscopy and multi-photon microscopy, 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) and certified[CV1] for medical devices biocompatibility tests (DIN ISO 10993-5). 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 preanimal test system for penetration and distribution tests of chemicals under EU REACH regulations. Further questions in regard to cell differentiation and death, as well as tumor development and metastasis, can be studied with our model. Recently, vascular structures have been integrated into the skin model and the automated production of the avascular skin model could be achieved.
Another main focus is the further characterization of our 3D intestinal test system and the development of new intestinal disease models. Our accredited 2D intestinal test system with integrated colon carcinoma cells (Caco-2) is used for transport studies to validate the permeability of potential drug candidates and other compounds.
Additionally, we are developing methods for the creation of cardiovascular implants, regenerative therapies and 3D test systems. Due to the lack of regenerative potential in the adult cardiovascular system, we primarily work with human embryonic and induced-pluripotent stem cells, as well as complex bioreactor systems.
- Isolation and culture of primary cells from different tissues and species in accordance with current GLP or GMP regulations
- Biomaterial using tissue-specific extracellular matrix proteins
- Micro- or nano-structured material surfaces
- Skin and skin tumors, as well as intestinal and cardiovascular tissues
- Method development for constructing 3D organotypic cell cultures for in vitro test models or tissue reconstruction
- Biological and biologic matrices
- Tissue-specific, computer-driven bioreactors
- Establishing methods for the non-destructive characterization of cells and tissues by means of Raman spectroscopy and multiphoton microscopy
ADMET (absorption, distribution, metabolism, excretion and toxicity) are pharmacokinetic and toxicological properties that must be tested during drug development. Using our test systems, we are able to test these properties in a more human situation than animal experiments, with the hope to eventually replace animal tests, as required by the 3R’s initiative (replacement, refinement, and reduction).
Another goal is the use of our complex tissues as transplants in regenerative medicine. In our GMP manufacturing unit, we offer process development and manufacturing of autologous transplants (Advanced Therapy Medicinal Products, ATMPs) as Investigational Medicinal Products (IMPs). The first step involves establishing and verifying the specific manufacturing process for a particular ATMP, which is then adapted to regulatory demands. The final step is applying for the manufacturing authorization for investigational medicinal products. At present, we possess manufacturing authorization for an autologous cartilage transplant
Range of services
- Cell culture technology of primary human cells and specific cell culture media
- In vitro testing of biocompatibility according to DIN ISO 10993-5
- Cell biology analysis
- Molecular-biological, histological and immunohistological methods
- Flow cytometry (FACS), including cell sorting
- Modern digital image processing techniques such as microdissection
- Raman spectroscopy and multiphoton microscopy
- Establishing of various 3D tissue models
- Accredited for REACH testing
- Alternatives to animal testing in cosmetics R&D
- ADMET testing in substance and drug screening
- Target screening for new therapeutics and infection biology
- Development of specific computer-controlled bioreactor systems for the culture of 3D tissue models
- Process development, manufacturing and testing of cell and gene therapeutics as investigational medicinal products or ATMPs (phase I/II clinical studies)
Infrastructure and technical equipment
- Cell culture laboratories conforming to safety levels S1 and S2 of the German GenTSV (genetic engineering safety regulations)
- State-of-the-art equipment such as an inverse fluorescence microscope, a multiphoton microscope system, a Raman spectroscope, FACS and PALM microdissection instrumentation
- GMP production unit (cleanrooms, separate quality control area, storage facilities)