3R competencies
The Bio Engineering Laboratory (BEL) develops microfluidic devices for use with microtissues of different cell types to investigate effects of pharmacological compounds and basics of tissue-tissue interaction (“body-on-a-chip” concepts). Moreover, BEL develops complementary metal-oxide semiconductor (CMOS)-based high-density microelectrode arrays to study neuronal function under normal and pathological conditions at subcellular resolution. In a recent project, the group established a microfluidic device that hosts embryonic stem cells (ES) and liver spheroids to assess the potentially harmful effects of drug or compound metabolites on embryonic development. The developed device provides additional information as compared to the embryonic stem cell test (EST).
Key words: ES cells, iPS cells, microtissue, brain organoids, microfluidic system, hanging drops, tilting device, microelectrodes, biosensors
The Laboratory for Bone Biomechanics (LBB) investigates various aspects of bone biology from molecular to the whole-organ level using different model systems and approaches. In the currently on-going projects, the group is not only establishing comprehensive in vitro systems such as 3D bioprinted bone micro-scaffolds, 3D hydrogel-based bone organoids, for reliable recapitulation of in vivo features, but also developing in silico models of bone adaptation and fracture healing directly based on micro-structural images produced using time-lapsed micro-computed tomography (micro-CT). Finally, for addressing questions related to mechanical loading, several in-house bioreactors were created for in vitro cell culture.
Key words: 3D hydrogel-based bone cultures and co-cultures, microscale scaffolds, bone organoids, 3D bioprinting, time-lapsed microCT imaging, bioreactors for mechanical stimulation, in silico predictive models, human primary cells to model rare bone diseases
The Laboratory of Food Biotechnology has developed a number of in vitro gut fermentation models, in which the fecal microbiota isolated from healthy or diseased donors (human and animals) can be cultured under carefully controlled conditions. In addition, different cell models are used to test cellular responses to microbiome metabolites so that and specific mechanisms can be explored. Such approaches are successfully used for understanding the mechanisms of food components, microbes and xenobiotics on the gut microbiota and host response, and for developing microbiome-based therapy for different gut-associated diseases.
Key words: fermentation, cell culture, in vitro gut models, microbiome-host interactions, PolyFermS continuous colonic models, 3D organoid Colon Chip
The Laboratory for Biosensors and Bioelectronics (LBB) a scalable technology for creating small neural networks with controlled oriented connections, which can be used to study fundamental neuroscience questions such as memory and learning. This can also serve as a promising “brain on a chip” approach to drug discovery for brain diseases. Further 3D cell cultures and disease models can be created using special hydrogel gradients in microtiter plates. Moreover LBB has also developed a new bioanalytical tool that allows performing immunoassays in tiny (1µL) samples for small animal analysis that help reducing the number of lab animals required by an experiment. These technologies are commercialized by the ETH spin-offs Ectica and ImmuProbe, respectively.
Key words: controlled neural networks, biosensors, bioanalytics, single cells, microsampling
The Tissue Engineering and Biofabrication group carries out translational research for cartilage regeneration applying such technologies as additive manufacturing (3D bioprinting) and electrospinning. The main research areas include bioinks engineering, exploration of suitable biomaterials for 3D cultures of different cell types (chondrocytes, neurons) and investigation of new cell types for regenerative medicine purposes (human infant chondrocytes).
Key words: hydrogel engineering, bioinks, 3D cartilage cultures, chondrocytes, human iPSc, 3D bioprinting, electrospinning, cryoelectrospinning, 2 photon litography
The Laboratory of Orthopedic Biomechanics studies fundamental principles of tendon biology employing self-established tissue explant models and a range of developed in vitro models in both 2D and 3D (“tendon-on-a-chip”). These models are typically combined with mechanical stimuli, often using self-designed mechanical bioreactors.
Key words: cell-matrix interaction, collagen matrix biology, PEG hydrogels, tendon, tendon explant model,
tendon-on-chip, 3D co-culture, tri-culture, 3D fibroblast-matrix models, mechanical bioreactors, in silico models of cell motility, human cells
Multi-scale Functional and Molecular Imaging group has been instrumental in the development of multi-spectral optoacoustic tomography (MSOT), transforming this novel imaging technology from the initial demonstration of technical feasibility, through validation in small animal studies, all the way toward its successful clinical translation. At present, MSOT is rapidly finding its place as a powerful new clinical diagnostics tool in the fields of oncology, dermatology, cardiovascular and inflammatory diseases.
Key words: functional and molecular imaging, longitudinal observations, multimodal imaging, multi-spectral optoacoustic tomography, biomedical imaging, photoacoustics, microscopy, ultrasound
In the line with the main research scope on investigation of epigenetic control mechanisms in a cell fate during development, Professor's Wutz group successfully established a protocol for generation of haploid mouse embryonic stem cells (haESC). The developed method not only allows investigation of X-chromosome inactivation, but also can be used as a tool for genome wide screening, thus, resulting in potential reduction of generated mutant mice. Additionally, the group tested anti-inhibin antibodies and confirmed their efficiency for increase of ovulated oocytes.
Key words: ES cells, mouse haploid ES (haES), stem cells sorting
The Laboratory for Food Immunology aims to tackle principles of interaction between the immune system and intestine and apply obtained knowledge for development novel oral vaccines and food-based therapeutics. In collaboration with Prof. Martin Ackermann the group established an anaerobic microfluidic system, which let scientists study the behavior of intestinal bacteria on a single cell level under carefully manipulated environmental conditions. In combination with computer simulation, this approach provides valuable data about mechanisms of host-microbe interactions and allows significant reduction of further required in vivo experiments.
Key words: anaerobic microfluidic chamber, computer simulation (modelling), microbiome-host interactions
The Experimental Continuum Mechanics group characterizes the mechanical behavior of soft biological tissues such as fetal membranes, pericardium or skin as well as diverse biomedical materials with appropriate mathematical models, based on experimental data and computer simulation. The generated predictive models are essential for improvement and development of new implants and devices as well as diagnostic tools.
Key words: constitutive models, large deformations, soft biological tissue, biomedical materials, implants, biomedical device development, computer simulation, bioreactors for cell culturing
The Computational Biology Group (CoBi) investigates the processes of organogenesis and establishes in silico spatio-temporal models based on data obtained from in vitro 3D organ cultures combined with high-resolution imaging.
Key words: in silico organogenesis (kidney, lung, pancreas, CNS, limb), 3D organization of epithelia, mechanisms of cell-cell signaling, tissue simulation, computer and image-based modelling
The Laboratory for Orthopaedic Technology studies intervertebral disc (IVD) degeneration and develops new regenerative strategies using 3D ex vivo culture models derived from coccygeal discs of large animals* as well as human lumbar IVD cell cultures. Self-produced bioreactors are used to apply simulated physiological mechanical loads.
*bovine tissue from the food industry
Key words: primary chondrocytes, primary IVD cells, scaffolds, 3D ex vivo IVD organ culture model, bioreactors for mechanical load, 3D human lumbar IVD cell cultures, A-disc explants, computer modelling, mechanical characterisation
The main research focus of Prof. Zamboni's lab is a quantitative analysis of metabolites and identification a mechanistic basis of metabolic changes resulted from genetic alternations, drug administration, stress conditions and other environmental challenges. Thanks to the employed approaches, the maximum information can be obtained from a single sample, while the results can be delivered practically in real-time.
Key words: metabolomics, stable isotope flux analysis, mass spectrometry, bottom-up approach, high-throughput screening, quantitative approach, computational data integration
One of the research focuses of the Product Development Group Zurich is the improvement and development of medical devices, which can be promptly delivered in clinics. In this line, the group passionately develops so called “test benches” and “phantoms” in order to imitate pathophysiological conditions and, thus, to create, improve and reproducibly test biomedical devices under accurate conditions. For example,test bench was built that can mimic hydrocephalus. It comprises a hardware interface and an accurate mathematical model that is derived from in-vivo and clinical data. This (hardware-in-the-loop concept) is successfully used to assess the functionality of current shunts that are implanted for the treatment of hydrocephalus. The same concept is currently employed in the hybrid mock circulation for the development of novel functionalities for left ventricular assist devices. Finally, the group is working on improvements of the quality and standardization of in-vitro skin models fabrication, which can be widely used for fundamental research.
Key words: mathematical modelling, hydrocephalus simulator, in vitro skin models, hybrid mock circulation, silicone heart phantom