An artificial liver sinusoid with a microfluidic endothelial‐like barrier for primary hepatocyte culture

Abstract

Primary hepatocytes represent a physiologically relevant model for drug toxicity screening. Here, we created a biologically inspired artificial liver sinusoid with a microfluidic endothelial-like barrier having mass transport properties similar to the liver acinus. This unit consisted of a cord of hepatocytes (50 Â 30 Â 500 mm) fed by diffusion of nutrients across the microfluidic endothelial-like barrier from a convective transport vessel (10 nL/min). This configuration sustained rat and human hepatocytes for 7 days without an extracellular matrix (ECM) coating. Experiments with the metabolism mediated liver toxicant diclofenac showed no hepatotoxicity after 4 h and an IC 50 of 334 AE 41 mM after 24 h.

A microfluidic perfusion platform for cultivation and screening study of motile microalgal cells

“…[17][18][19] We developed here a perfusion system for the cultivation of free floating cells by incorporating pneumatic microvalves. Two pieces of the patterned PDMS for fluidic channels/chambers and pneumatic valves were overlayered with precise alignment to prepare a PDMS perfusion chip with a 2 Â 4 array of chambers and mounted on a glass slide coated with PDMS adhesive layer.…”

Organ-on-a-Chip Platforms for Drug Delivery and Cell Characterization: A Review

“…(7) To investigate the mechanical and other interactions in the cellular microenvironment, the organ-on-a-chip platform has been developed. On the basis of the advancements of polymer material science and nanofabrication technology, such platforms can facilitate the study of cell-cell, (24) cell-ECM, (30) and cell-tubular flow (31) interactions. The platforms allow scientists to carry out drug screening and delivery tests and analyses.…”

“…(51) Liver-on-a-chip platforms have been developed to understand the liver function better and to study drug hepatotoxicity and metabolism. (31,52,53) A microfluidic device fabricated to mimic the permeable sinusoidal endothelial barrier between hepatocytes and the liver sinusoid (31) includes three main sectionsa central channel to contain the hepatocytes, a microfluidic sinusoid barrier patterned with a set of narrow (2 mm wide) microchannels to model the endothelial barrier, and a microfluidic convection channel surrounding the barrier [ Fig. 4(a)].…”

Chip-based liver equivalents for toxicity testing – organotypicalness versus cost-efficient high throughput

“…67 The hepatotoxic effect of diclofenac on human primary hepatocytes cultured in this device could be mimicked. 68 Diclofenac is a model compound for metabolism-mediated hepatotoxicity, as it exhibits its toxic effect only after prolonged exposure (24 h) to metabolically competent cells. Furthermore, the high cell density allowed for an enhanced cell-cell contact with tight junctions and desmosomes.…”