scholarly journals A Hepatic Scaffold from Decellularized Liver Tissue: Food for Thought

Biomolecules ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. 813 ◽  
Author(s):  
Stefania Croce ◽  
Andrea Peloso ◽  
Tamara Zoro ◽  
Maria Antonietta Avanzini ◽  
Lorenzo Cobianchi

Allogeneic liver transplantation is still deemed the gold standard solution for end-stage organ failure; however, donor organ shortages have led to extended waiting lists for organ transplants. In order to overcome the lack of donors, the development of new therapeutic options is mandatory. In the last several years, organ bioengineering has been extensively explored to provide transplantable tissues or whole organs with the final goal of creating a three-dimensional growth microenvironment mimicking the native structure. It has been frequently reported that an extracellular matrix-based scaffold offers a structural support and important biological molecules that could help cellular proliferation during the recellularization process. The aim of the present review is to underline the recent developments in cell-on-scaffold technology for liver bioengineering, taking into account: (1) biological and synthetic scaffolds; (2) animal and human tissue decellularization; (3) scaffold recellularization; (4) 3D bioprinting; and (5) organoid technology. Future possible clinical applications in regenerative medicine for liver tissue engineering and for drug testing were underlined and dissected.

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.


Author(s):  
Wei-Jiun Lin ◽  
Kuo-Wei Chang ◽  
Min-Yu Chiang ◽  
Shih-Kang Fan ◽  
Cheng-Hsien Liu

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mariliis Klaas ◽  
Kaidi Möll ◽  
Kristina Mäemets-Allas ◽  
Mart Loog ◽  
Martin Järvekülg ◽  
...  

AbstractSolution blow spinning (SBS) has recently emerged as a novel method that can produce nano- and microfiber structures suitable for tissue engineering. Gelatin is an excellent precursor for SBS as it is derived mainly from collagens that are abundant in natural extracellular matrices. Here we report, for the first time the successful generation of 3D thermally crosslinked preforms by using SBS from porcine gelatin. These SBS mats were shown to have three-dimensional fibrous porous structure similar to that of mammalian tissue extracellular matrix. In pharma industry, there is an urgent need for adequate 3D liver tissue models that could be used in high throughput setting for drug screening and to assess drug induced liver injury. We used SBS mats as culturing substrates for human hepatocytes to create an array of 3D human liver tissue equivalents in 96-well format. The SBS mats were highly cytocompatible, facilitated the induction of hepatocyte specific CYP gene expression in response to common medications, and supported the maintenance of hepatocyte differentiation and polarization status in long term cultures for more than 3 weeks. Together, our results show that SBS-generated gelatin scaffolds are a simple and efficient platform for use in vitro for drug testing applications.


2021 ◽  
Author(s):  
Zohreh Farrar ◽  
Arezoo Khoradmehr ◽  
Kazuyoshi Tsutsui ◽  
Yuanyuan He ◽  
Neda Baghban ◽  
...  

Abstract Free of Acrylamide Sodium Fast Free-of-Acrylamide Clearing Tissue (FACT) is a developed technique using no acrylamide for clearing tissues. As the lipid removal normally is a harmful process and it causes loss of biological molecules such as proteins and on the other hand is crucial for transparency and efficient antibody staining throughout the whole tissue especially for microscopy and imaging, the FACT technique is suitable since it makes chemical bonding of membrane and intracellular proteins with the extracellular matrix creating a massive three-dimensional (3D) matrix and structural support to fortify the tissue during processing. Compared to other acrylamide-based techniques, FACT requires less labor, toxic, and harmful chemicals. Here we describe protocols encompassing every angle and dimension of the FACT protocol for antibody staining and imaging of whole-cleared tissues while preserving the structure and increasing the image quality. The entire protocol includes tissue perfusion, fixation, clearing, antibody staining, Refractive Index Matching (RIM), microscopy, and imaging; this timing varies due to the size, weight, different kind of tissues and the type of immunostaining. This technique has been favorably performed on different types of tissues for molecular interrogation analysis of large tissues.


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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