Engineered intestinal organoids

The use of the heterogeneous and ill-defined 3D cell culture platform Matrigel has facilitated organoid culture with impressive versatility but is not without limitations. In particular, culture in Matrigel results in highly variable organoids that are difficult to control in terms of size and shape, hindering quantitative analysis. Our approach to organoid culture and differentiation involves the use of synthetic matrices to direct morphogenesis through tunable biochemical and mechanical signals. We spatiotemporally pattern these cues using photoinduced degradation, viscoelasticity, and bond formation to study how intestinal stem cell colonies respond to alterations in geometric confinement, mirroring processes observed in vivo. Looking ahead, we seek to identify unique mechanosensing pathways that influence crypt cellularity and design material platforms to enable uniform microtissues amenable to high-throughput screening.
Collaborators: (Anschutz Medical Campus), (Genentech), (Korea University), (EPFL, Roche)