3D flow-focusing microfluidic biofabrication: one-chip-fits-all hydrogel fiber architectures

The microfluidic manipulation of hydrogels is a powerful tool to recapitulate functional biological ar- chitectures. A wide range of flow configurations and chip designs have been employed to create mi- crofibers with increasingly complex shapes and compositions requiring individually engineered setups. Distinctly, we demonstrate how one single 3D hydrodynamic flow-focusing chip can be used to obtain a continuous flow of hydrogel precursors, which rearrange themselves based on viscosity and applied pressures. These can crosslink into fibers with a variety of new multi-compartment shapes down to yet- unreported minimal dimensions. To prove the potential of 3D flow-focusing for the biofabrication of com- plex, multi-compartment structures, we tuned material properties and flow conditions to obtain ribbon- like cancer/basement-membrane/stroma models; core-shell vascular-like structures and networks; and multi-chemistry fibers integrating stem cells, biomaterials, and pro-differentiation hydrophobic molecule depots. This innovative biofabrication method can be valuable for the recreation of a broad range of com- plex biological architectures and micro-modeling of distinct 3D environments.The authors acknowledge financial support from the European Research Council, grant ERC-2012-ADG 20120216-321266 (project ComplexiTE). C. F. G. acknowledges scholarship PD/BD/135253/2017 from Fundação para a Ciência e Tecnologia (FCT)