Module 4. Dynamics of interacting cell-material systems

Conventional cell-based assays used in drug discovery and diagnostic developments are typically static and thus not representative of the spatially complex and highly dynamic context present in living tissues. State-of-the-art organ-on-a-chip systems enable dynamic modulation of liquid cell culture media, but are made from materials (e.g. glass or PDMS) that are unconducive to promote stem cell self-organization into functional miniature tissues termed ‘organoids’. In Module 4 we strive to develop a versatile microfluidic platform to reproducibly derive organoids from primary stem (and tumor) cells directly on-chip and within bioinspired hydrogels, and manipulate their development and state in situ via magnetically and optically manipulatable, stimuli-responsive polymersomes. These smart colloidal shuttles will afford the spatiotemporally controlled delivery of key signaling factors involved in tissue (and tumor) development. The microfluidic chip technology will be deployed to 1) elucidate the cellular and molecular mechanisms by which tissue organization emerges through stem cell self-organization, and 2) study how tissue organization gets disrupted in cancer. Module 4 aims at bringing together research from all previous modules to tackle two pertinent biological and clinical challenges that have thus far escaped conventional in vitro and in vivo approaches.