scholarly journals Microporous membrane-based liver tissue engineering for the reconstruction of three-dimensional functional liver tissues in vitro

Biomatter ◽  
2012 ◽  
Vol 2 (4) ◽  
pp. 290-295 ◽  
Author(s):  
Junichi Kasuya ◽  
Kazuo Tanishita
2020 ◽  
Vol 2020 ◽  
pp. 1-22 ◽  
Author(s):  
Zhidong Jia ◽  
Yuan Cheng ◽  
Xinan Jiang ◽  
Chengyan Zhang ◽  
Gaoshang Wang ◽  
...  

In vitro 3D hepatocyte culture constitutes a core aspect of liver tissue engineering. However, conventional 3D cultures are unable to maintain hepatocyte polarity, functional phenotype, or viability. Here, we employed microfluidic chip technology combined with natural alginate hydrogels to construct 3D liver tissues mimicking hepatic plates. We comprehensively evaluated cultured hepatocyte viability, function, and polarity. Transcriptome sequencing was used to analyze changes in hepatocyte polarity pathways. The data indicate that, as culture duration increases, the viability, function, polarity, mRNA expression, and ultrastructure of the hepatic plate mimetic 3D hepatocytes are enhanced. Furthermore, hepatic plate mimetic 3D cultures can promote changes in the bile secretion pathway via effector mechanisms associated with nuclear receptors, bile uptake, and efflux transporters. This study provides a scientific basis and strong evidence for the physiological structures of bionic livers prepared using 3D cultures. The systems and cultured liver tissues described here may serve as a better in vitro 3D culture platform and basic unit for varied applications, including drug development, hepatocyte polarity research, bioartificial liver bioreactor design, and tissue and organ construction for liver tissue engineering or cholestatic liver injury.


2019 ◽  
Vol 6 (3) ◽  
pp. 59 ◽  
Author(s):  
Shicheng Ye ◽  
Jochem W.B. Boeter ◽  
Louis C. Penning ◽  
Bart Spee ◽  
Kerstin Schneeberger

Bioengineered livers are promising in vitro models for drug testing, toxicological studies, and as disease models, and might in the future be an alternative for donor organs to treat end-stage liver diseases. Liver tissue engineering (LTE) aims to construct liver models that are physiologically relevant. To make bioengineered livers, the two most important ingredients are hepatic cells and supportive materials such as hydrogels. In the past decades, dozens of hydrogels have been developed to act as supportive materials, and some have been used for in vitro models and formed functional liver constructs. However, currently none of the used hydrogels are suitable for in vivo transplantation. Here, the histology of the human liver and its relationship with LTE is introduced. After that, significant characteristics of hydrogels are described focusing on LTE. Then, both natural and synthetic materials utilized in hydrogels for LTE are reviewed individually. Finally, a conclusion is drawn on a comparison of the different hydrogels and their characteristics and ideal hydrogels are proposed to promote LTE.


2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Birong Wang ◽  
Qinggang Hu ◽  
Tao Wan ◽  
Fengxiao Yang ◽  
Le Cui ◽  
...  

Galactosylated chitosan (CTS) has been widely applied in liver tissue engineering as scaffold. However, the influence of degree of substitution (DS) of galactose moieties on cell attachment and mechanical stability is not clear. In this study, we synthesized the lactose-modified chitosan (Lact-CTS) with various DS of galactose moieties by Schiff base reaction and reducing action of NaBH4, characterized by FTIR. The DS of Lact-CTS-1, Lact-CTS-2, and Lact-CTS-3 was 19.66%, 48.62%, and 66.21% through the method of potentiometric titration. The cell attachment of hepatocytes on the CTS and Lact-CTS films was enhanced accompanied with the increase of galactose moieties on CTS chain because of the galactose ligand-receptor recognition; however, the mechanical stability of Lact-CTS-3 was reduced contributing to the extravagant hydrophilicity, which was proved using the sessile drop method. Then, the three-dimensional Lact-CTS scaffolds were fabricated by freezing-drying technique. The SEM images revealed the homogeneous pore bearing the favorable connectivity and the pore sizes of scaffolds with majority of 100 μm; however, the extract solution of Lact-CTS-3 scaffold significantly damaged red blood cells by hemolysis assay, indicating that exorbitant DS of Lact-CTS-3 decreased the mechanical stability and increased the toxicity. To sum up, the Lact-CTS-2 with 48.62% of galactose moieties could facilitate the cell attachment and possess great biocompatibility and mechanical stability, indicating that Lact-CTS-2 was a promising material for liver tissue engineering.


2021 ◽  
Vol 8 (11) ◽  
pp. 185
Author(s):  
Amit Panwar ◽  
Prativa Das ◽  
Lay Poh Tan

Liver-associated diseases and tissue engineering approaches based on in vitro culture of functional Primary human hepatocytes (PHH) had been restricted by the rapid de-differentiation in 2D culture conditions which restricted their usability. It was proven that cells growing in 3D format can better mimic the in vivo microenvironment, and thus help in maintaining metabolic activity, phenotypic properties, and longevity of the in vitro cultures. Again, the culture method and type of cell population are also recognized as important parameters for functional maintenance of primary hepatocytes. Hepatic organoids formed by self-assembly of hepatic cells are microtissues, and were able to show long-term in vitro maintenance of hepato-specific characteristics. Thus, hepatic organoids were recognized as an effective tool for screening potential cures and modeling liver diseases effectively. The current review summarizes the importance of 3D hepatic organoid culture over other conventional 2D and 3D culture models and its applicability in Liver tissue engineering.


Molecules ◽  
2019 ◽  
Vol 24 (9) ◽  
pp. 1762 ◽  
Author(s):  
Juan Cui ◽  
Huaping Wang ◽  
Qing Shi ◽  
Tao Sun ◽  
Qiang Huang ◽  
...  

Three-dimensional (3D) tissue models replicating liver architectures and functions are increasingly being needed for regenerative medicine. However, traditional studies are focused on establishing 2D environments for hepatocytes culture since it is challenging to recreate biodegradable 3D tissue-like architecture at a micro scale by using hydrogels. In this paper, we utilized a gelatin methacryloyl (GelMA) hydrogel as a matrix to construct 3D lobule-like microtissues for co-culture of hepatocytes and fibroblasts. GelMA hydrogel with high cytocompatibility and high structural fidelity was determined to fabricate hepatocytes encapsulated micromodules with central radial-type hole by photo-crosslinking through a digital micromirror device (DMD)-based microfluidic channel. The cellular micromodules were assembled through non-contact pick-up strategy relying on local fluid-based micromanipulation. Then the assembled micromodules were coated with fibroblast-laden GelMA, subsequently irradiated by ultraviolet for integration of the 3D lobule-like microtissues encapsulating multiple cell types. With long-term co-culture, the 3D lobule-like microtissues encapsulating hepatocytes and fibroblasts maintained over 90% cell viability. The liver function of albumin secretion was enhanced for the co-cultured 3D microtissues compared to the 3D microtissues encapsulating only hepatocytes. Experimental results demonstrated that 3D lobule-like microtissues fabricated by GelMA hydrogels capable of multicellular co-culture with high cell viability and liver function, which have huge potential for liver tissue engineering and regenerative medicine applications.


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