Markus Rimann

Microtissues (such as organoids or spheroids) are useful to model healthy or diseased human tissues and organs, with application in drug testing, tissue engineering, and personalized medicine. To characterize their morphology and phenotype, microtissues are often monitored using histology and high-resolution imaging. While this technique is well-established and standard for macroscopic tissue sections, it remains challenging to execute and has low throughput in the context of these sub-millimeter structures, mainly due to the fact that their size makes them difficult to locate within the embedding medium. To enhance the efficiency of microtissue histology, we developed an acoustofluidic device that arranges microtissues in a coplanar arrangement within HistoGel, a widely used embedding medium. Pre-patterning microtissues within HistoGel streamlines downstream processing by positioning the centers of mass of the microtissues at a pre-defined plan in the sample, simplifying sectioning, labeling, and imaging. We validated the method using differently sized HepG2 microtissues and tumor microtissues from osteosarcoma cells (Saos-2, MG-63, HOS), demonstrating that this method can be applied to different microtissue shapes, sizes, and types, without modifying established post-processing techniques. Our approach substantially enhances the microtissue histology workflow and broadens possibilities for microtissue analysis.

A key to enhance the low translatability of preclinical drug discovery are in vitro human three-dimensional (3D) microphysiological systems (MPS). Here, we show a new method for automated engineering of 3D human skeletal muscle models in microplates and functional compound screening to address the lack of muscle wasting disease medication. To this end, we adapted our recently described 24-well plate 3D bioprinting platform with a printhead cooling system to allow microvalve-based drop-on-demand printing of cell-laden Matrigel containing primary human muscle precursor cells. Mini skeletal muscle models develop within a week exhibiting contractile, striated myofibers aligned between two attachment posts. As an in vitro exercise model, repeated high impact stimulation of contractions for 3 h by a custom-made electrical pulse stimulation (EPS) system for 24-well plates induced interleukin-6 myokine expression and Akt hypertrophy pathway activation. Furthermore, the known muscle stimulators caffeine and Tirasemtiv acutely increase EPS-induced contractile force of the models. This validated new human muscle MPS will benefit development of drugs against muscle wasting diseases. Moreover, our Matrigel 3D bioprinting platform will allow engineering of non-self-organizing complex human 3D MPS.

A happy coincidence brought Dr Markus Rimann from ZHAW Waedenswil together with Dr Andreas Meyer from the start-up FGen and PD Dr Emanuela Felley-Bosco, Molecular Oncologist at Zurich University Hospital, to develop a technology platform for the manufacture and high throughput analysis of single mesothelioma spheroids. Armin Picenoni, former student in Chemistry for the Life Sciences at ZHAW, confirmed everything in writing his Master Thesis on this Innosuisse project.

Bioprinting is the technology of choice for realizing functional tissues such as vascular system, muscle, cartilage and bone. In the future, bioprinting will influence the way we engineer tissues and bring it to a new level of physiological relevance. That was the topic of the 2017 TEDD Annual Meeting at ZHAW Waedenswil on 8th and 9th November. In an exciting workshop, the two companies regenHU Ltd. and CELLINK gave us an insight into highly topical applications and collaborations in this domain.