Journal
ACS BIOMATERIALS SCIENCE & ENGINEERING
Volume 6, Issue 4, Pages 2469-2477Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsbiomaterials.9b01735
Keywords
gelatin bioink; cell-printing technology; cell delivery; liver; 3D liver fibrosis-on-a-chip
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Funding
- National Research Foundation of Korea (NRF) - Korean government (MSIP) [2019R1A3A3005437]
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Liver fibrosis is a critical liver disease which can lead to liver cirrhosis, cancer, and liver failure. Among various etiological factors, activated stellate cells are a major factor that can induce liver fibrosis. Several studies have presented in vitro models to identify drugs for liver fibrosis; however, there are still limitations in terms of the 2D culture conditions, random co-culture of liver cells, and lack of extracellular matrix components. Therefore, a 3D liver fibrosis-on-a-chip was developed with three liver cell types (hepatocytes, activated stellate cells, and endothelial cells) using a novel cell-printing technique with gelatin bioinks, which were used to deliver each nonparenchymal liver cell type as a multilayer construct. Liver fibrosis-specific gene expression, collagen accumulation, cell apoptosis, and reduced liver functions caused by activated stellate cells were also evaluated. Furthermore, previously reported chemicals were added to the 3D liver fibrosis-on-a-chip to examine the downregulation of activated hepatic stellate cells. In conclusion, the developed 3D liver fibrosis-on-a-chip could be used as a potential in vitro model in the research field.
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