关键词: 肝脏, 器官芯片, 类器官, 疾病研究, 药物评价

Abstract:

The liver plays an important role in maintaining normal physiological activities of the human body. It has a complex structure and multiple functions, including blood glucose regulation, protein synthesis, detoxification and drug metabolism. Although traditional two-dimensional cell culture and animal models have been used to study liver physiology or pathology, there are still some limitations in truly reflecting the microenvironment of human liver and its response to drugs. The development of liver models in vitro is essential for disease research and effective drug testing. Organ-on-a-chip is a groundbreaking technology that has emerged in recent years by merging engineering and biological approaches. It can replicate the essential structural and functional features of human tissues and organs in vitro. Recently, in vitro liver tissue models created with organ chips have shown an impressive ability to closely mimic the liver tissue microenvironment and offer high-throughput capabilities. These models have been extensively applied in liver regenerative medicine, disease research, and drug testing, highlighting their significant potential in the biomedical field. Therefore, in this paper, we provide a comprehensive overview of the limitations inherent in traditional liver in vitro models, particularly in their ability to replicate complex physiological microenvironments and accurately reproduce liver-specific functions. It delineates the design strategies, technical characteristics, and research advancements associated with novel liver in vitro models, with a particular emphasis on organ-on-a-chip technologies. The discussion focuses on the key elements crucial for the biomimetic construction of liver organ-on-a-chip systems and the simulation of liver tissue microenvironments. These elements include the integration of multicellular components, the replication of liver sinusoid and lobule structures, the establishment of biochemical factor gradients, and the incorporation of fluid dynamics. Moreover, it provides an outlook on the future development of highly physiologically relevant liver organ-on-a-chip and microphysiological systems, considering the integration of advanced techniques such as organoids, biomaterials, and gene editing.

Key words: human liver, organ-on-a-chip, organoid, disease modeling, drug testing