Organoids are 3D multicellular structures, derived from stem cells, that self-organise and assemble into simplified replicas of the organs from they are derived. While not all organs and tissue types have been recapitulated as organoid models to date, for many organs they have been highly useful tools for the study of development and disease, as well as drug discovery. However, commercially available cell culture matrices do not promote the growth of all organ and tissue types as organoids, one of the principal reasons being their static nature. In the human body, growing tissues and organs remodel the adjacent extracellular matrix to create optimal conditions for their own growth and differentiation. Static matrices do not provide this dynamic feedback for the growing cells, thus contributing to a lack of accuracy or viability in the resulting organoid. A dynamic matrix, that altered its viscoelasticity in responsive to cellular cues, and in turn altered mechanical stimuli on growing cellular structures would be highly beneficial for the wider exploitation of organoid models.

Funded by an SNSF Spark grant, we have begun to explore the development of environmentally responsive cell culture matrices from catch bond-crosslinked hydrogels. We are interested in assessing to what extent these, so-called, CatchGels can adapt their viscoelastic behaviour as a function of chemical and mechanical cues from organoids in culture. Such dynamic culture matrices would not only promote accurate organoid culture, but also provide the possibility to tune the proliferation and differentiation of cell types within the organoid using an organoid-matrix feedback loop. Our goal is not only to create healthy and accurate organoid models, but also to be able to recapitulate disease states for modelling and drug discovery. The exciting outcome of this is, by knowing the ways in which mechanics influences differentiation patterns in our artificial systems, we can also shed some light on the mechanics of disease states.

Team Members:

Yves Erdin, Elisa Sohrmann (MSc intern, alumna)

Cooperation Partners:

University Children’s Hospital Basel, University Hospital Basel, University of Zurich

Funding:

Swiss National Science Foundation (Spark)