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

摘要：

肝脏具有复杂结构和多种功能，包括血糖调控、蛋白合成、解毒和药物代谢等，在维持人体正常生理活动中起着重要作用。传统的二维细胞培养和动物模型已被广泛用于肝脏生理或疾病研究，但它们在反映人体组织真实微环境和对药物反应等方面仍存在一定局限。因此，建立高仿真度肝脏体外模型对于肝病研究、药效与毒性评价至关重要。本文概述了传统肝脏体外模型在实现近生理复杂微环境模拟、肝组织特异性功能准确复现等方面的局限性，总结了以器官芯片为代表的新型肝脏体外模型的设计策略、技术特点及其在生物医学领域的研究进展。文中重点介绍了肝器官芯片仿生构筑和实现肝组织微环境模拟的关键要素，包括多细胞组分、肝窦/肝小叶结构、生化因子梯度和流体因素等，并对未来结合其他先进手段（如类器官、生物材料和基因编辑等）等，建立高度生理相关性的肝器官芯片和微生理系统的发展前景予以展望。

关键词: 肝脏, 器官芯片, 类器官, 疾病研究, 药物评价