1. Supplemental Figure 1 Experimental Design: Our experiments incorporate hepatocytes and the full compliment of non-parenchymal cells to better recapitulate the hepatic niche. A schematic of the optimized experimental plan is depicted above.

2. Supplemental Figure 2 Acute-phase response enhanced in the presence of NPCs: Freshly resected human hepatocytes (hHep) and nonparenchymal cells (NPC) were plated in the microphysiologic system and maintained with supernatant sampling through 15 days. Cells were stimulated on day 14 with LPS (1 ug/mL) for 24 hours. Acute-phase protein production of alpha-1 anti-trypsin and fibrinogen by hepatocytes was measured by ELISA (n=1).

3. Supplemental Figure 3 Donor (B)Donor (C)Donor (A) Donor (D)Donor (B) MDA MB 231 Donor (C)Donor (B) Donor (C)Donor (B) MDA MB 231 MCF7 RFP/Hoechst MCF7 RFP/Ki67/EdU A. B. Representative images from different donors of spontaneous growth attenuation in a sub- population of breast cancer cell lines: A. MCF7 (top; 1000 cells/well) and MDA-MB-231 (bottom; 100 cells/well) seeded on day 3 of hHep and NPC culture and maintained through day 15. Scaffolds were fixed and stained. Cancer cells: red, Hoechst: blue. B. On day 11 and 13 of culture, EdU (20 µM) was added to fresh culture medium before harvesting scaffolds on day 15 (96 hours for incorporation). Scaffolds were fixed and immunostained. Cancer cells: red, Ki67: blue, EdU: green. Solid white arrow: attenuated cell, Dashed white arrow: proliferating cell. 300 μm