A three‐dimensional microfluidized liver system to assess hepatic drug metabolism and hepatotoxicity

Corrado, Brunella; Gregorio, Vincenza De; Imparato, Giorgia; Attanasio, Chiara; Urciuolo, Francesco; Netti, Paolo A.

doi:10.1002/bit.26902

Cited by 25 publications

(34 citation statements)

References 66 publications

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“…The liver‐on‐a‐chip systems have also been utilized for hepatotoxicity evaluation of various drugs or toxicants used in a high‐throughput manner . In addition, a perfusable liver‐on‐a‐chip model integrated with gelatin‐porous microbeads was constructed to evaluate ethanol‐induced cytotoxicity, providing a potential platform for drug development and toxicity research …”

Section: Hydrogels In Organs‐on‐a‐chip Engineeringmentioning

confidence: 99%

Advances in Hydrogels in Organoids and Organs‐on‐a‐Chip

et al. 2019

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The major motivation is to better mimic human physiology and functions at multiscales from the molecular to the cellular, tissue, organ or even whole organism level. Current model systems primarily rely on the monolayer cell cultures and animal models. Simplistic monolayer cultures have their advantages, but they are often significantly different in gene expression, epigenetics, and cell function compared to native 3D tissues. [1,2] Also, they often lack cell-cell and cell-matrix interactions, [2,3] leading to the absence of tissue specific properties. Although animal models are widely used in biomedical research, they fail to faithfully predict human responses in a physiologically relevant manner due to the significant species divergences. [4] The limitations of these systems have provided an impetus for the development of alternative cell-based 3D models in vitro that better resemble the complex functionalities of living organs. Over the last several years, organoids and organ-on-a-chip (OOC), representing the major technological breakthrough, have emerged as two distinct model systems to achieve the same goal of building 3D organotypic models in vitro by bridging the gap between animal models and monolayer cultures. These engineered models are different in terms of cell source, tissue composition, architectural variability, functional features, scales, cellular fidelity, etc. Organoids, primarily evolving from developmental principles, refer to 3D multicellular tissues by self-organization of stem cells or organ-specific progenitors, which can recapitulate the intricate architectures and functionalities of in vivo organs. [5][6][7] Recent breakthroughs in organoid technology have enabled the successful generation of a variety of human organoids, such as the brain, [8,9] intestine, [10,11] liver, [12] kidney, [13,14] lung, [15] etc. These near physiological 3D organoids have garnered momentum for their potential applications in human organ development and disease modeling, drug screening and regenerative medicine. The explosion of organoids research has been catalyzed by the significant progress of stem cell biology and availability of human stem cells. In contrast, the OOC, relying on the bioengineering design principle, is a miniaturized in vitro model that can recreate the functional units of living organs on a microfluidic cell culture device using predifferentiated cells, often cell lines. [1,16] The OOC is primarily evolved from the convergence of tissue engineering and microfabricated technologies, which is characterized by the capability to simulate cellular microenvironment by precise control over fluid flow, mechanical forces and biochemical factors. [4,17] Remarkable progress has been made Significant advances in materials, microscale technology, and stem cell biology have enabled the construction of 3D tissues and organs, which will ultimately lead to more effective diagnostics and therapy. Organoids and organs-on-a-chip (OOC), evolved from developmental biology and bioengineering principles, have e...

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Section: Hydrogels In Organs‐on‐a‐chip Engineeringmentioning

confidence: 99%

Advances in Hydrogels in Organoids and Organs‐on‐a‐Chip

et al. 2019

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“…HepG2 cells were cultured on GPMs in spinner flasks (Integra), as previously reported with slight modifications (Corrado et al, 2019). Briefly, 35 mg of GPMs were loaded with 5.25 × 10 6 cells (30 cell/GPM ratio).…”

Section: Hepg2-µtps Developmentmentioning

confidence: 99%

“…With the perspective of elucidating the inter-organs crosstalk with a more physiological functional 3D tissues, we reported a development of a novel Intestine-Liver-on-Chip (InLiver-OC) consisting of two directly interconnected chambers (Intestine-compartment and Liver-compartment) that enable the culture of a 3D Human Intestine Model (3D-HIM) as well as 3D liver microtissues (HepG2-µTPs) in order to simulate the physiological mechanism of the first-pass metabolism of orally-ingested compounds. Bottom-up approach was used to fabricate the 3D-HIM provided with an endogenous ECM (Imparato et al, 2013) and HepG2-µTPs, as previously reported (Corrado et al, 2019). The combination of such physiological relevant 3D models with microfluidic technology allowed us to investigate the protective role of the intestine on liver injury, analyzing the 3D-HIM hyper-permeability as well as the intestinal stroma remodeling.…”

Section: Introductionmentioning

confidence: 99%

Intestine-Liver Axis On-Chip Reveals the Intestinal Protective Role on Hepatic Damage by Emulating Ethanol First-Pass Metabolism

Gregorio

Telesco

Corrado

et al. 2020

Front. Bioeng. Biotechnol.

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Intestine-Liver-on-chip systems can be useful to predict oral drug administration and first-pass metabolism in vitro in order to partly replace the animal model. While organ-on-chip technology can count on sophisticated micro-physiological devices, the engineered organs still remain artificial surrogates of the native counterparts. Here, we used a bottom-up tissue engineering strategy to build-up physiologically functional 3D Human Intestine Model (3D-HIM) as well as 3D Liver-microtissues (HepG2-µTPs) in vitro and designed a microfluidic Intestine-Liver-On-Chip (InLiver-OC) to emulate first-pass mechanism occurring in vivo. Our results highlight the ethanol-induced 3D-HIM hyper-permeability and stromal injury, the intestinal prevention on the liver injury, as well as the synergic contribution of the two 3D tissue models on the release of metabolic enzymes after high amount of ethanol administration.

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“…Good news from the field of skin regeneration: the work on bioengineered skin substitutes has been selected by the editorial board as the cover story of the issue of December 2019 (www.mdpi.com/2077-0383/8/12). The article, presented by a group active in the field of dermal substitutes [13] and three-dimensional tissue-like models [14], is focused on the analysis of the most Cancer, and more specifically the usage of nanoparticles (NP) both for multimodal imaging and as contrast agents (CAs), is the topic of a review [8] which highlights the advantages of using NP-based PET/MRI multimodal imaging in tumor diagnosis and characterization. Additionally, these nanosystems can be applied to theranostics in the very prominent scenario of personalized medicine.…”

mentioning

confidence: 99%

“…Good news from the field of skin regeneration: the work on bioengineered skin substitutes has been selected by the editorial board as the cover story of the issue of December 2019 (www.mdpi.com/ 2077-0383/8/12). The article, presented by a group active in the field of dermal substitutes [13] and three-dimensional tissue-like models [14], is focused on the analysis of the most modern strategies to overcome the scarring process and promote skin regeneration, by implanting an engineered dermis capable of recapitulating the architecture and presenting molecular signals similarly to the native dermis [10].…”

mentioning

confidence: 99%