Establishment Of An Intestine And Liver System Based On Bio-microfluidic Chips

In vitro models of biological tissues are indispensable tools for unraveling human physiology and pathogenesis. Organs-on-Chips based on microfluidic chips reconstitute tissue arrangements observed in living organs in order to study physiology in an organ-specific context and to develop specialized in vitro disease models by culturing or assembling cell into microfluidic chips. The technologies reviewed have the potential to be more predictive human relevant models for toxicity and efficacy testing. It could applied to predict some aspects of absorption, distribution, metabolism and excretion (ADME) of many drug candidates.In this study, we designed an intestine with liver bio-microfluidic chip systems which can simulate the absorption and metabolism of the organism. Then build a double fluid channel three-dimensional PDMS chip containing multilayer cells, which could meet different needs according to the arrangement of cells. We designed two chips with different arrangement of cells and the action process of the two drugs on the two chips was determined. (1) We cultured Caco-2 cells on the first layer of the chip to simulate intestinal structure; Rat hepatic parenchymal cells were cultured on the opposite layer to simulate the liver structure. Hela cells were cultured on lower layer to simulate tumor cells. This model is used to simulated the process intestinal absorption-liver metabolism and reaching the tumor of cyclophosphamide drugs. The results show that the aldophosphamide, hepatic metabolism product of cyclophosphamide, shows an obvious inhibitory effect to Hela cells. (2) We cultured Caco-2 cells on the first layer of the chip to simulate the intestinal structure; HUVEC cells were cultured on the opposite layer to simulate vascular structure; Rat primary hepatocytes were cultured on lower layer to simulate liver structure. This model is used to simulat the process that acetaminophen (APAP) enters into organism orally then arrive live metabolism through intestinal absorption and blood vessels. The experimental results show that Caco-2 has a good transfer function for APAP, intestinal module and liver module all have metabolic capacity of APAP. The metabolic production-APG and APS could be determined. The liver part of the chip, we have carried out the construction of complex liver model on the chip and established the liver damage model with hydrogen peroxide. The experimental results show that the bio-microfluidic chip can be used to simulate the absorption and metabolism of some drugs in vivo. The construction of complex liver model makes the liver chip of the bionic organ in vitro closer to the liver structure of the living body; The liver damage model further broadens the application of the chip in the pharmaceutical field.