State-of-the-art advancements in Liver-on-a-chip (LOC): Integrated biosensors for LOC

Abstract

Liver models are vital for the liver diseases and drug research as many novel drugs. However, traditional liver models cannot meet this need, mainly because they cannot replicate the complex physiological structure and microenvironment of the liver, especially the O2 and nutrient gradients. Liver-on-a-chip (LOC), based on microfluidic technology, can not only closely simulate the physiological structure and microenvironment of the liver through the design of suitable microchannels, but can also incorporate advanced biosensors with high sensitivity and potential for rapid responses to microenvironmental signals and liver function indicators. Nevertheless, LOCs have not been widely exploited for liver disease research or the screening of drugs for hepatotoxicity because of considerable professional barriers. In this review, we comprehensively summarize recent progress in LOC development and the embedding of biosensors into LOCs. We first introduce the physiological characteristics and microenvironment of the liver and then summarize the fabrication process and advantages of LOCs. We subsequently focus on recent advances relating to three-dimensional (3D) hepatocyte organization and the simulation of hepatic sinusoids and lobules in LOCs and further systematically summarize the research progress in biosensor-integrated LOCs. Finally, we discuss the potential value of LOCs and the challenges facing their exploitation. In conclusion, this review provides insights into the design and development of biosensor-integrated LOCs aiming to promote further research into this promising platform.