The native liver as inspiration to create superior <i>in vitro</i> hepatic models

Carpentier, Nathan; Urbani, Luca; Dubruel, Peter; Vlierberghe, Sandra Van

doi:10.1039/d2bm01646j

Cited by 4 publications

(3 citation statements)

References 227 publications

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“…3D-printing of biomaterials has gained increasing interest in the fields of tissue engineering [1], drug delivery [2] as well as to support the development of in vitro models [3,4]. A major challenge in the field involves the establishment of printable inks starting from materials with suitable rheological properties [5].…”

Section: Introductionmentioning

confidence: 99%

Optimization of hybrid gelatin-polysaccharide bioinks exploiting thiol-norbornene chemistry using a reducing additive

Carpentier,

Parmentier,

Van der Meeren

et al. 2024

Biomed. Mater.

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Thiol-norbornene chemistry offers great potential in the field of hydrogel development, given its step growth crosslinking mechanism. However, limitations exist with regard to deposition-based bioprinting of thiol-containing hydrogels, associated with premature crosslinking of thiolated (bio)polymers resulting from disulfide formation in the presence of oxygen. More specifically, disulfide formation can result in an increase in viscosity thereby impeding the printing process. In the present work, hydrogels constituting norbornene-modified dextran (DexNB) combined with thiolated gelatin (GelSH) are selected as case study to explore the potential of incorporating the reducing agent tris(2-carboxyethyl)phosphine (TCEP), to prevent the formation of disulfides. We observed that, in addition to preventing disulfide formation, TCEP also contributed to premature, spontaneous thiol-norbornene crosslinking without the use of UV light as evidenced via 1H-NMR spectroscopy. Herein, an optimal concentration of 25 mol% TCEP with respect to the amount of thiols was found, thereby limiting auto-gelation by both minimizing disulfide formation and spontaneous thiol-norbornene reaction. This concentration results in a constant viscosity during at least 24 hours, a more homogeneous network being formed as evidenced using atomic force microscopy while retaining bioink biocompatibility as evidenced by a cell viability of human foreskin fibroblasts exceeding 70 % according to ISO 10993-6:2016.

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Section: Introductionmentioning

confidence: 99%

Optimization of hybrid gelatin-polysaccharide bioinks exploiting thiol-norbornene chemistry using a reducing additive

Carpentier,

Parmentier,

Van der Meeren

et al. 2024

Biomed. Mater.

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“…Furthermore, several biochemical and biophysical properties of the native liver are largely preserved, with intact ECM and growth factors within, supporting stem cell differentiation into liver cells. [11][12][13][14][15][16] Cells can only survive within a limited distance (up to ~1 mm) from a source of nutrients. Since decellularised organs are usually several millimetres thick, there are challenges associated with adequate nutrition supply and oxygen perfusion when used in ex vivo conditions, frequently resulting in non-functional areas or necrotic regions.…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Rat liver extracellular matrix and perfusion bioreactor culture promote human amnion epithelial cell differentiation towards hepatocyte-like cells

Campinoti,

Almeida,

Goudarzi

et al. 2023

J Tissue Eng

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Congenital and chronic liver diseases have a substantial health burden worldwide. The most effective treatment available for these patients is whole organ transplantation; however, due to the severely limited supply of donor livers and the side effects associated with the immunosuppressive regimen required to accept allograft, the mortality rate in patients with end-stage liver disease is annually rising. Stem cell-based therapy aims to provide alternative treatments by either cell transplantation or bioengineered construct transplantation. Human amnion epithelial cells (AEC) are a widely available, ethically neutral source of cells with the plasticity and potential of multipotent stem cells and immunomodulatory properties of perinatal cells. AEC have been proven to be able to achieve functional improvement towards hepatocyte-like cells, capable of rescuing animals with metabolic disorders; however, they showed limited metabolic activities in vitro. Decellularised extracellular matrix (ECM) scaffolds have gained recognition as adjunct biological support. Decellularised scaffolds maintain native ECM components and the 3D architecture instrumental of the organ, necessary to support cells’ maturation and function. We combined ECM-scaffold technology with primary human AEC, which we demonstrated being equipped with essential ECM-adhesion proteins, and evaluated the effects on AEC differentiation into functional hepatocyte-like cells (HLC). This novel approach included the use of a custom 4D bioreactor to provide constant oxygenation and media perfusion to cells in 3D cultures over time. We successfully generated HLC positive for hepatic markers such as ALB, CYP3A4 and CK18. AEC-derived HLC displayed early signs of hepatocyte phenotype, secreted albumin and urea, and expressed Phase-1 and -2 enzymes. The combination of liver-specific ECM and bioreactor provides a system able to aid differentiation into HLC, indicating that the innovative perfusion ECM-scaffold technology may support the functional improvement of multipotent and pluripotent stem cells, with important repercussions in the bioengineering of constructs for transplantation.

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The Material World of 3D‐Bioprinted and Microfluidic‐Chip Models of Human Liver Fibrosis

Carvalho,

Bansal,

Barrias

et al. 2023

Advanced Materials

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Biomaterials are extensively used to mimic the cell‐matrix interactions, which are essential for cell growth, function and differentiation. This is particularly relevant when developing in vitro disease models of organs rich in extracellular matrix, like the liver. Liver disease involves a chronic wound‐healing response with formation of scar tissue known as liver fibrosis. At early stages, liver disease can be reverted, but as disease progresses, reversion is no longer possible, and there is no cure. Research for new therapies is hampered by the lack of adequate models that replicate the mechanical properties and biochemical stimuli present in the fibrotic liver. Fibrosis is associated with changes in the composition of the extracellular matrix that directly influence cell behavior. Biomaterials could play an essential role in better emulating the disease microenvironment. In this paper, the recent and cutting‐edge biomaterials used for creating in vitro models of human liver fibrosis are revised, in combination with cells, bioprinting and/or microfluidics. These technologies have been instrumental to replicate the intricate structure of the unhealthy tissue and promote medium perfusion that improves cell growth and function, respectively. A comprehensive analysis of the impact of material hints and cell‐material interactions in a 3D context is provided.This article is protected by copyright. All rights reserved

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The native liver as inspiration to create superior in vitro hepatic models

Abstract: This work gives an overview of the current hepatic models and their shortcomings while suggesting strategies for superior future models.

Cited by 4 publications

References 227 publications

Optimization of hybrid gelatin-polysaccharide bioinks exploiting thiol-norbornene chemistry using a reducing additive

Optimization of hybrid gelatin-polysaccharide bioinks exploiting thiol-norbornene chemistry using a reducing additive

Rat liver extracellular matrix and perfusion bioreactor culture promote human amnion epithelial cell differentiation towards hepatocyte-like cells

The Material World of 3D‐Bioprinted and Microfluidic‐Chip Models of Human Liver Fibrosis

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