Fig. 1: On-chip micro-vascularization enabled by soft microfluidics.

a 3D printed tissue culture chip designed for eight multiplexed 3D soft microfluidic capillary grids. Inset: microfluidic capillary grid fabricated on a plastic baseplate and diagram of working principle. b Microfluidic capillary grid (left) and close up image of the same grid showing individual hydrogel capillaries (right). The manufacturing process generates capillary grids with about 90% success rate, as assessed over more than  one hundred produced devices. c Microvessel 3D printing of microfluidic grid using high-resolution 2-photon stereo-lithography with non-swelling photo-polymerizable hydrogel precursors enables reproduction of features as small as 10 µm. Printed examples demonstrate an array of cylinders of various outer diameters (top row) and wall thickness (columns) - units in µm. d CAD image of microfluidic grid (left) with capillaries shown in red and the structural components shown in gray. The edge of the structure makes up a “basket” that can be filled (right) with cell aggregates (spheroids) which merge and produce a solid tissue incorporating hydrogel capillaries. e Hydrogel capillaries are readily permeable. 25 µM of fluorescein, perfused through the microfluidic grid embedded in Matrigel, across the capillary walls and saturates the gel within several minutes. Color scale represents the range of fluorescein concentrations from 0 to 25 µM. f Process of tissue generation. Photograph of an empty capillary grid with 200 µl pipette tip visible above the grid (left, scale bar 500 µm), close up image of the grid seeded with hPSC spheroids (middle, scale bar 250 µm) manually dispensed from the pipette shown on the left image, image of the spheroids (right, scale bar 250 µm) fused into a solid tissue after 24–36 h of culturing on chip. The top row schematically represents the same process, where spheroids and the resulting tissue are shown in blue.