Injectable hydrogels based on glycyrrhizin, alginate, and calcium for three-dimensional cell culture in liver tissue engineering

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.

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Effective Cell Seeding and Three-Dimensional Cell Culture for Bone Tissue Engineering

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2014.1204 ◽

2014 ◽

Vol 4 (7) ◽

pp. 573-578 ◽

Cited By ~ 2

Author(s):

Min Hwei Ng ◽

Shiplu Roy Chowdhury ◽

Mahboob Morshed ◽

Kok Keong Tan ◽

Guan Huat Tan ◽

...

Keyword(s):

Tissue Engineering ◽

Cell Culture ◽

Bone Tissue Engineering ◽

Bone Tissue ◽

Three Dimensional ◽

Cell Seeding ◽

Dimensional Cell

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Modifying three-dimensional scaffolds from novel nanocomposite materials using dissolvable porogen particles for use in liver tissue engineering

Journal of Biomaterials Applications ◽

10.1177/0885328212445404 ◽

2012 ◽

Vol 28 (2) ◽

pp. 250-261 ◽

Cited By ~ 6

Author(s):

Hussamuddin Adwan ◽

Barry Fuller ◽

Clare Seldon ◽

Brian Davidson ◽

Alexander Seifalian

Keyword(s):

Tissue Engineering ◽

Liver Tissue ◽

Three Dimensional ◽

Nanocomposite Materials ◽

Liver Tissue Engineering

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Multicellular Co-Culture in Three-Dimensional Gelatin Methacryloyl Hydrogels for Liver Tissue Engineering

Molecules ◽

10.3390/molecules24091762 ◽

2019 ◽

Vol 24 (9) ◽

pp. 1762 ◽

Cited By ~ 7

Author(s):

Juan Cui ◽

Huaping Wang ◽

Qing Shi ◽

Tao Sun ◽

Qiang Huang ◽

...

Keyword(s):

Tissue Engineering ◽

Regenerative Medicine ◽

Liver Function ◽

Cell Viability ◽

Liver Tissue ◽

Three Dimensional ◽

Microfluidic Channel ◽

Cell Types ◽

Liver Tissue Engineering ◽

Multiple Cell

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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Tissue Engineering in Liver Regenerative Medicine: Insights into Novel Translational Technologies

Cells ◽

10.3390/cells9020304 ◽

2020 ◽

Vol 9 (2) ◽

pp. 304 ◽

Cited By ~ 6

Author(s):

Zahra Heydari ◽

Mustapha Najimi ◽

Hamed Mirzaei ◽

Anastasia Shpichka ◽

Marc Ruoss ◽

...

Keyword(s):

Tissue Engineering ◽

Regenerative Medicine ◽

Liver Tissue ◽

Three Dimensional ◽

Public Health Problem ◽

Dimensional Structure ◽

Important Public Health Problem ◽

Novel Technologies ◽

Liver Tissue Engineering ◽

New Findings

Organ and tissue shortage are known as a crucially important public health problem as unfortunately a small percentage of patients receive transplants. In the context of emerging regenerative medicine, researchers are trying to regenerate and replace different organs and tissues such as the liver, heart, skin, and kidney. Liver tissue engineering (TE) enables us to reproduce and restore liver functions, fully or partially, which could be used in the treatment of acute or chronic liver disorders and/or generate an appropriate functional organ which can be transplanted or employed as an extracorporeal device. In this regard, a variety of techniques (e.g., fabrication technologies, cell-based technologies, microfluidic systems and, extracorporeal liver devices) could be applied in tissue engineering in liver regenerative medicine. Common TE techniques are based on allocating stem cell-derived hepatocyte-like cells or primary hepatocytes within a three-dimensional structure which leads to the improvement of their survival rate and functional phenotype. Taken together, new findings indicated that developing liver tissue engineering-based techniques could pave the way for better treatment of liver-related disorders. Herein, we summarized novel technologies used in liver regenerative medicine and their future applications in clinical settings.

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