Figure 1

HeLiVa platform design. (A) Modular design of the culture platform, with interlocking culture chambers (the same external design, different internal designs) connected to each other and the microfluidic channels for medium perfusion. A single top and bottom plate are formed by connecting the individual chamber tops and bottoms, and sealed together to form a culture platform. (B) Chamber design for a cardiac microtissue forming around a sugar lattice (that dissolves to leave vascular network channels) and two posts (designed to subject cardiac tissue to mechanical strain, and also to serve for optical measurement of force generation by the cells), between two electrodes for electrical stimulation (the whole row of chambers shares a single pair of electrodes). (C) Chamber design for a liver microtissue, also forming around a sugar lattice (that dissolves to leave vascular network channels). For all chambers, ports are provided for fluid inlets and outlets and sample retrieval. (D) Platforms with cardiac microtissues. (E) Liver chamber. (F) Sugar lattices. (G) Contractile cardiac microtissue grown from induced pluripotent stem (iPS) cells after 4 weeks of cultivation. (H) Even propagation of electrical signals through cardiac tissue obtained from human endothelial stem cells cultured in a hydrogel derived from porcine heart tissue, measured by printed microelectrodes. (I) Vascular channels were generated by three-dimensional printing of sugar-based sacrificial filaments and coated by human endothelial cells. (J) The endothelium forms a tight barrier between lumen and interstitium (not shown), and when exposed to a gradient of angiogenic factors undergoes angiogenic sprouting that leads to new perfusable vascular networks. (K) Mature sprout stained for podocalyxin (red). Below are cross-sections of the tip cell (showing no lumen or spatial podocalyxin localization) and stalk (showing podocalyxin staining at the apical side). (L) Neovessel. (M) iPS cell-derived endothelial cells cultured on an OP9 feeder layer, staining for VE-cadherin (VE-Cad) and CD31 (merged image) and 4',6'-diamino-2-phenylindole (DAPI; blue). (K), (L) Images reproduced with permission [23].