Liver-On-A-Chip
Bionic microfluidic chips integrate bionics, compactness, and efficiency. In the design of a liver chip, the size of the chip is only a few centimeters. Microprocessing tools are used to create a fine microchannel network that drives the flow of microculture fluid in it, accurately simulating the microenvironment of liver tissue in vivo, fully reflecting the interaction between cells and cells, as well as between cells and growth factors, thereby mimicking functions similar to those of liver organs in vivo.
Types of Livers-on-Chips
- 2D Liver-on-a-Chip
Compared with traditional 2D culture, a 2D liver chip system can accurately control the amount of fluid infusion, supply nutrients, and remove harmful substances at the same time so as to achieve continuous long-term culture.
- Tissue-like 3D Liver-on-a-Chip
The advantages of 3D microstructure development are mainly reflected in two aspects. First, compared with 2D cultured hepatocytes, 3D-cultured hepatocytes can easily maintain their characteristics and function and improve their proliferation ability in a 3D culture environment. In addition, in a 3D culture environment, the isolated hepatocytes showed close to the liver function in vivo, and could maintain the characteristics of differentiation for a long time. Second, 3D culture is more conducive to the formation of liver ultrastructures, such as liver villi, bile tubules, and so on.
- ECM-based 3D Liver-on-a-Chip
Cell encapsulation technology means that different types of cells are enclosed in a matrix composed of semi-permeable membranes and can be cultured for a long time with their cellular functions. This encapsulation technique enables 3D liver models to be used for cell transplantation without attack by the host immune system and to analyze cell behavior in 3D ECM. Cell therapy based on this technique, capable of performing the complex functions of the liver, offers a potential alternative to whole organ transplantation.
- Ultrastructural 3D Liver-on-a-Chip
For liver tissue engineering, the key is to generate a specific liver ultrastructure in the microtissue, which should include hepatic sinusoids, bile ducts, endothelial pores, and vasculature, etc. Enhanced efficient uptake of oxygen and nutrients, and the excretion of toxic metabolic waste are necessary for long-term survival of liver tissue. Liver tissues with an ultrastructure can also be used as a source of grafts because they already have an internal ultrastructure that can be immediately vascularized by the host vasculature upon transplantation.
Liver-on-a-Chip Technology
- Microfluidics
- Soft Etching Technology
- 3D Printing Technology
Liver-on-a-Chip Applications
- Drug Screening and Toxicity Testing
The liver is the main part of metabolism in the body and plays an irreplaceable role in drug metabolism. Therefore, it is also easily affected by drug toxicity. So far, human liver slices or animal models have been widely used in drug screening and toxicity testing. However, the available human tissues are limited, and the results of animal models are often not well applicable to humans. Therefore, an in vitro model of the human liver, i.e. liver-on-a-chip, is highly desired in the pharmaceutical field.
- Liver Disease Model
In liver disease, hepatic fibrosis has multiple causes, most of which are characterized by the accumulation of ECM leading to liver failure and portal hypertension. At present, research on viral infection, liver cancer, and other liver diseases mainly uses animal models or 2D cell culture models, and the establishment of micro-platforms and 3D liver-on-a-chip can help better understand the above-mentioned disease mechanisms, so as to find treatment options.
- Bioartificial Liver and Liver Reconstruction Engineering
For patients with liver failure, liver transplantation is the only therapeutic chip available at present. Engineered liver microtissue can be used for transplantation to maintain and reconstruct liver function. The engineered liver microtissue can temporarily replace part of liver function during the recovery of the patient's own liver function or while waiting for transplantation, which wins time for the recovery of liver function and the regeneration of hepatocytes.
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Reference
- Dalsbecker, P.; et al. Liver-on-a-chip devices: the pros and cons of complexity. American Journal of Physiology-Gastrointestinal and Liver Physiology. 2022 Sep 1;323(3):G188-204.
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