Fig. 1.

Better liver physiological mimicry: the role of fluid flow (a) Increased shear stress after partial hepatectomy leads to enhanced HGF production and proliferation of hepatocytes. (b) Higher HGF production was recapitulated on a chip with endothelial cells lined vessel subjected to shear stress of 3.95 dyne/cm² (n = 3 devices, Mean ± SEM, significance level was determined by *p < 0.05, ***p < 0.001, ****p < 0.0001, one-way ANOVA with Tukey’s multiple comparisons test). (c) The two-channel LoC device commercialized by Emulate Inc., operated with the dynamic flow on both top and bottom channels separated by a membrane at the same flow rate (30 μl/h) for toxicity prediction. (d) Higher functional activity of sandwich cultured hepatocytes in LoC: (i) Species-specific albumin production rates captured in LoC, which were higher than static plate culture, (ii) Higher CYP3A activity in LoC. CYP3A data was compared with Sidak’s multiple comparisons test (n = 3∼17 independent chips). Albumin data was compared with Sidak’s multiple comparisons test (n = 3∼14 independent chips, n = 3∼9 independent wells in plate). Significance level was determined by: *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. All error bars were presented as Mean ± SEM. Panels (b) is adapted under terms of the CC-BY license from Ref. [47] Copyright 2022, PNAS. Panel (b) was rearranged and redrawn after removing channel dimensions. Panel (c) is adapted under terms of the CC-BY license from Ref. [13] Copyright 2022, Nature. In Panel (c), the device designs were redrawn indicating the flow rates. Panel (d) is reproduced with permission from Ref. [55] Copyright 2019, AAAS.