Multiphasic microgel-in-gelmaterials to recapitulate cellular mesoenvironments in vitroElectronic supplementary information (ESI) available: Experimental details, design and performance of the co-flow microfluidic device, cell-induced degradation of microbeads, monophasic 3D prostate cancer model, PC3 cells embedded into microbeads: spheroid formation and live/dead assay data. See DOI: 10.1039/c9bm01009b

Multiphasic in vitromodels with cross-scale heterogeneity in matrix properties and/or cellular composition can reflect the structural and compositional complexity of living tissues more faithfully, thereby creating new options for pathobiology and drug development studies. Herein, a new class of tunable microgel-in-gelmaterials is reported that build on a versatile platform of multifunctional poly(ethylene glycol)-heparin gel types and integrates monodisperse, cell-laden microgels within cell-laden bulk hydrogel matrices. A novel microfluidic approach was developed to enable the high-throughput fabrication of microgels of in situadjustable diameters, stiffness, degradability and biomolecular functionalization. By choosing structure and composition of the microgel and the bulk gel compartments independently, our microgel-in-gelarrangements provide cross-scale control over tissue-mimetic features and pave the way for culture systems with designed mesoenvironmental characteristics. The potentialities of the introduced approach are exemplarily shown by creating a reductionistic in vitromodel of vascularized prostate cancer tissue.