Microengineering the Liver: Strategies for Constructing Functional Liver-on-a-Chip Devices

Several human studies show positive signals, while research methods and sample sizes continue to develop.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Reliable in vitro liver models are indispensable for researching liver diseases and developing medications. Present 2D/3D cell cultures and animal models inadequately replicate the intricacy of living systems and in vivo conditions, resulting in impaired cellular functions. They also fail to emulate tissue-like architectures, which undermines their precision. Meanwhile, animal models present species differences, making real-time observation of dynamic results inconvenient and raising serious ethical concerns. Therefore, there is an urgent need to develop alternative tissue models with biomimetic human pathophysiology to bridge the gap between clinical trials and traditional human and animal models. Liver-on-a-chip (LOC) technology, based on microfluidics, is an innovative in vitro modeling device that can replicate the microstructures and tissue-tissue interfaces of specific liver functional units, simulating organ and tissue-level physiological activities. This review summarizes recent strategies and breakthroughs in LOC technologies, from biomimetic tissues and extracellular matrix construction in liver microphysiological systems to diverse LOC development approaches. Furthermore, we highlight key advances in functional LOC platforms, including 3D bioprinting, vascularization strategies, and the incorporation of liver buds and organoids to enhance physiological relevance. The

Evidence level

Several human studies show positive signals, while research methods and sample sizes continue to develop.

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