3D tissue models
Fraunhofer Institute for Interfacial Engineering and Biotechnology
New drugs and substances have to be tested before market authorization as regards their quality, safety and efficacy. For lack of equivalent alternative methods, animal experiments are an important standard instrument in drug research. Due to species-specific differences, however, the animal experiments are not in every case suitable for the authorization of new substances or the adaptation of new therapies to humans.
Therefore the Fraunhofer IGB has been increasingly engaged in recent years in the development of alternative human test systems that reflect the complex characteristics of the body and that permit the investigation of a material according to the ADMET criteria (absorption, distribution, metabolism, excretion and toxicity). These test systems are based on in vitro cultivated human primary cells, cell lines or adult stem cells. In order to ensure the functionality of these cells in vitro, culture conditions must be created that are similar to the natural microenvironment of the cell in the body. This requires, in addition to the sufficient supply of the cells, co-culture with other cell types as well as the provision of a suitable carrier structure.
This allows the cells not only adhesion and three-dimensional growth, but also considerably affects parameters such as metabolic activity, viability, division, morphology and differentiation status and thus, ultimately, the function of the tissue.
The Department of Cell and Tissue Engineering is specialized in constructing such human three-dimensional tissues. 3-D test systems for various applications and questions such as substance testing or differentiation tests of stem cells, have already been developed.
Fields of research
Good to know
ADMET stands for absorption, distribution, metabolism, excretion and toxicity - criteria that largely determine the pharmacokinetic and toxicological properties of a potential drug. The examination of the ADMET parameters enables the investigation of compound absorption, for example in the digestive tract or distributed via the blood stream. Biochemical reactions in the body can lead to the ineffective or even toxic degradation of compounds. It is therefore important to examine how substances are metabolized and excreted.
Tissues of both animal and human origin can be treated with chemical solutions to remove all of the original cells. These treated tissues create a natural and biocompatible support structures that are used by the Fraunhofer IGB as 3D tissues.
Cells that line the intestinal tube and control the uptake (absorption) of nutrients and drugs.
A structure of connective tissue that provides structural support for tissues in the body.
Metabolically active cells of the liver.
A protrusion of an organ or the fascia of an organ through the wall of the cavity that normally contains it.
- Human cells:
Cells that originate from the human body.
- in vitro:
(latin) Studies that are conducted using components of an organism that have been isolated from their usual biological surroundings.
- in vivo:
(latin) Studies involving a whole, living organism.
- Porcine cells:
Cells that originate from pigs.
REACH refers to a new chemical regulation that was put in place on June of 2007. It requires the investigation of new and old chemicals for their toxicity. REACH stands for Registration, Evaluation, Authorization and Restriction of Chemicals. Our models are designed for testing chemicals according to the new EU chemicals regulation, some of which are already accredited.
The process by which body tissue develops proliferating capillaries and blood vessels.
Skin from the Factory – Automated Tissue Engineering on Demand:
“Mass Customized Organ Replicates – Tissue Engineering on Demand”
To meet the demand for cost-effective and standardized in-vitro test systems, scientists at the Fraunhofer IGB, IPT, IPA and IZI, joined together on a project funded by the Fraunhofer Future Foundation (Fraunhofer-Zukunfsstiftung) to automate the manufacturing process. The process chain for the production of two-layer tissue models has already been fully automated.
Development and evaluation of new therapies for chronic skin diseases
The demographic changes in industrialized countries have shown a growing number of people needing care and a simultaneous decline in the number of available nurses. This development can only be helped by improved care, reduced costs through increased efficiency in therapeutic methods and an expansion of patient self-sufficiency. The aim of the Fraunhofer “markets of tomorrow” project is to develop cost-effective therapies for chronic skin diseases.
Establishment of a white skin cancer model for the development and optimization of new topical treatments – SkinCancer
As the number of skin cancer cases increases, there has been an increase in the development of new topical treatments for skin cancer that aim to destroy cancer tumors, which may completely replace the need for surgery. To date, there are no appropriate human test systems for the quick and effective development of new therapies. As part of the project SkinCancer funded by the Fraunhofer-Gesellschaft (MEF program), a three-dimensional model of skin cancer will be established. In this case, the existing 3D skin model will be extended with the deliberate introduction of white skin cancer cells.
Molecular and cell-based systems for the risk assessment of nanomaterials
Nanoscale materials are integral for innovative developments across all sectors. They can differ in size and chemical properties. However, it is unclear on how some nanoparticles affect the human body. In collaboration with the Department of Molecular Biotechnology at the Fraunhofer IGB, the 3D skin model will be merged with the MESSAGE technology to establish a new method for nanopartical risk assessment. The project is funded by the Fraunhofer MEF program.
Intestine model - Platform for efficient epithelial transport for pharmaceutical applications via innovative particulate carrier systems
As part of the project "Efficient drug delivery in biological systems – BioMatVital" of the Federal Ministry of Education and Research (BMBF), the cooperation project "Petra" was born. Project partners from industry, research institutes and universities came together to jointly develop a platform for efficient epithelial transport for pharmaceutical applications by providing innovative, particulate carrier systems. Our part of this project is the integration of immune cells into our already developed 3D intestine model for the analysis of orally administered vaccine substances in the gut.
The kidney is the main excretory organ for drugs and their metabolites. Animal models are the current standard for the study of transport processes and renal toxic effects, because there are currently no validated human in vitro models. The Fraunhofer IGB is currently developing a model that will allow the study of transport and the potential toxic effects of substances or drug candidates in vitro with human primary cells.
PeTrA – Platform for efficient epithelial transport for pharmaceutical applications via innovative particulate carrier systems
New biofunctional polymers are going to make injections needless: The German Federal Ministry of Education and Research (BMBF) is funding an interdisciplinary research project to develop tablets and sprays for improved bioavailability and more comfortable administration of biopharmaceuticals and cancer immunotherapeutics.
- Cell isolation from primary material (biopsies)
- Cell characterization and sorting
- Construction, establishment and validation of threedimensional
static and dynamic testing systems
- Studies and testing services
- Histology, molecular- and cell-biological as well as biochemical
analyses of tissues and medium supernatants
Zu unserer Ausstattung gehören folgende Geräte und Technologien:
- Real-Time PCR
- Zellanalyse Expirion
Mertsching H, Hansmann J, Schanz J, Linke K., Brenner M, Michaelis J, Walles T, 2006: Vaskularisierte Trägersysteme für in vitro-Testsysteme. In: Beckmann D., Meister M. 13. Heiligenstätter Kolloquium. Technische Systeme für Biotechnologie und Umwelt. Heiligenstadt. Inst. f. Bioprozess- und Analysentechnik; ISBN-10: 3-00-018621-2; 47–55.
Walles T, Weimer M, Linke K, Michaelis J, Mertsching H, 2007: The potential of bioartificial tissues in oncology research and treatment. Onkologie 30(7); 388-394.
Thude S, Weimer M, Michaelis J, Mertsching H, 2008: Bioartifical tissues as a tool for development of tumor diagnostic methods. Endoskopie heute 21: 191-194.
Michaelis J, Schanz J, Hansmann J, Hampel M, Mertsching H, 2008: 3D- Zellsysteme – In vitro Testsysteme als Alternativmethoden zu Tierversuchen in der Pharmazeutischen und Chemischen Industrie. In: Conrad K., Lehmann W., Sack U., Schedler U. (Hrsg.) Multiparameteranalytik – Methoden, Applikationen, Perspektiven. Papst Science Publishers; ISBN-978-3-89967-461-3; 181-197.
Pusch J, 2009: Etablierung eines dynamisch kultivierten Darmgewebemodells: Ein neuer Ansatz bei der Entwicklung von Ersatz- und Ergänzungsmethoden zum Tierversuch auf Basis einer azellulären Trägerstruktur in vitro. Südwestdeutscher Verlag für Hochschulschriften, ISBN-10: 3838111931.
Schanz J, Pusch J, Hansmann J, Walles H, 2010: Vascularised human tissue models: a new approach for the refinement of biomedical research. J Biotechnol, 148(1): 56-63.
Schanz J, Walles H, Walles Th, 2012: Tissue Engineering. Menschliches Gewebe aus dem Labor. GIT Labor-Fachzeitschrift 2012: 360-362.