Microperfused Biomimetic Liver-on-a-Chip for High-Throughput Hepatotoxicity Screening.

Liver-on-a-chip has emerged as an effective tool for liver disease modeling and new drug development, while the current challenge lies in further mimicking liver physiological conditions. Here, inspired by the intricate architecture of hepatic lobules, a novel biomimetic vascularized liver-on-a-chip fabricated via high-precision 3D printing technology is presented. The chip features a capillary network with multiple micro-pores, ensuring a constant nutrient supply and efficient substance exchange within the cell environment through microfluidic perfusion. Under microperfusion conditions, human induced pluripotent stem cell-derived hepatocytes (hiPSC-Heps) exhibit superior physiological status and biological functionality compared to traditional 2D cultures. In addition, a comprehensive platform for assessing drug-induced liver injury (DILI) is established by integrating a concentration gradient chip, liver chips, and multicellular coculture technologies. This innovative platform effectively validates both acute and chronic hepatotoxic effects of acetaminophen (APAP). These findings demonstrate that the biomimetic vascularized liver-on-a-chip exhibits ideal physiological relevance and holds significant potential for applications in drug development and toxicity screening.