Tissue Systems

As the microtissues mostly include adherent cells (liver, heart, brain, pancreas etc.), one has to apply methods, where the spheroids do not adhere to surfaces and, thereby, remain intact over extended experimentation times. One possibility is to use the concept of "hanging-drop networks", in which the spheroids are located at the liquid-air-interface at the bottom of the hanging drops. The hanging drops are then interconnected via microfluidic channels to provide perfusion, supply of nutrients, dosage of compounds, or to interconnect them to other tissue types to realize "body-on-a-chip" arrangements.

Alternatively, one can host the spheroids in microtissue compartments in well plates, which are continuously tilted in a rocking-like motion, so that the spheroids constantly perform slight motions and cannot  adhere to the surface, which additionallly is coated with non-adhesive  films. The tilting motion also ensures perfusion and enables metabolic tissue interaction through the connection channels. Both approaches  allow for mimicking conditions of the human body and for predicting the  impact of new compounds on multi-organ systems.

Another group effort includes to develop microfluidics-based systems to enable high-resolution imaging of tumor invasion into complex tissue environments over several days. Organotypic slices retain the composition and cytoarchitecture of their tissue of origin, which renders them suitable for investigating tumor-microenvironment interactions. Tissue slices  are accommodated in a controlled microfluidic chamber, which allows for continuous optical access with high-numerical-aperture objectives while preserving sterility and tissue viability. We used the platform to investigate medulloblastoma invasion into organotypic cerebellar slices.