Usability of Polydimethylsiloxane-Based Microfluidic Devices in Pharmaceutical Research Using Human Hepatocytes.

A liver-on-a-chip (liver-chip) is a microfluidic device carrying liver cells such as human hepatocytes. It is used to reproduce a part of liver function. Many microfluidic devices are composed of polydimethylsiloxane (PDMS), which is a type of silicone elastomer. PDMS is easy to process and suitable for cell observation, but its high hydrophobicity carries the risk of drug absorption. In this study, we evaluated drug absorption to the PDMS device and investigated the drug responsiveness of human hepatocytes cultured in the PDMS device (hepatocyte-chips). First, the absorption rates of 12 compounds to the PDMS device were measured. The absorption rates of midazolam, bufuralol, cyclosporine A, and verapamil were 92.9, 71.7, 71.4, and 99.6%, respectively, but the other compounds were poorly absorbed. Importantly, the absorption rate of the compounds was correlated with their octanol/water distribution coefficient (log D) values (R2 = 0.76). Next, hepatocyte-chips were used to examine the response to drugs, which are typically used to evaluate hepatic functions. Using the hepatocyte-chips, we could confirm the responsiveness of drugs including cytochrome P450 (CYP) inducers and farnesoid X receptor (FXR) ligands. We believe that our findings will contribute to drug discovery research using PDMS-based liver-chips.

Miniaturized skeletal muscle tissue fabrication for measuring contractile activity.

The contractile function of skeletal muscle is essential for maintaining the vital activity of life. Muscular diseases such as muscular dystrophy severely compromise the quality of life of patients and ultimately lead to death. There is therefore an urgent need to develop therapeutic agents for these diseases. In a previous study, we showed that three-dimensional skeletal muscle tissues fabricated using the magnetic force-based tissue engineering technique exhibited contractile activity, and that drug effects could be evaluated based on the contractile activity of the skeletal muscle tissues. However, the reported method requires a large number of cells and the tissue preparation procedure is complex. It is therefore necessary to improve the tissue preparation method. In this study, a miniature device made of polydimethylsiloxane was used to simplify the production of contracting skeletal muscle tissues applicable to high-throughput screening. The effects of model drugs on the contractile force generation of skeletal muscle tissues prepared from mouse C2C12 myoblast and human induced pluripotent stem cells were evaluated using the miniature muscle device. The results indicated that the muscle device system could provide a useful tool for drug screening.