Construction of a liver sinusoid based on the laminar flow on chipand self-assembly of endothelial cells

摘要

The liver is one of the main metabolic organs, and nearly all ingested drugs will be metabolized by theliver. Only a small fraction of drugs are able to come onto the market during drug development, andhepatic toxicity is a major cause for drug failure. Since drug development is costly in both time andmaterials, an in vitro liver model that can accelerate bioreactions in the liver and reduce drugconsumption is imperative in the pharmaceutical industry. The liver on a chip is an ideal alternativefor its controllable environment and tiny size, which means constructing a more biomimetic model,reducing material consumption as well as promoting drug diffusion and reaction. In this study, takingadvantage of the laminar flow on chips and using natural degradable gel rat tail Collagen-I, weconstructed a liver sinusoid on a chip. By synchronously injecting two kinds of cell-laden collagen,HepG2-laden collagen and HUVEC-laden collagen, we formed two collagen layers with a clearborderline. By controlling the HUVEC density and injection of growth factors, HUVECs in collagenformed a monolayer through self-assembly. Thus, a liver sinusoid on a chip was achieved in a morebiomimetic environment with a more controllable and uniform distribution of discrete HUVECs.Viability, album secretion and urea synthesis of the live sinusoid on a chip were analysed on days 3, 5and 7 after collagen injection with acetaminophen treatment at 0 (control), 10 and 20 mM. The resultsindicated that our liver sinusoid on a chip was able to maintain bioactivity and function for at least 7 dand was beneficial for hepatotoxic drug screening.