Engineered Liver-On-A-Chip Platform to Mimic Liver Functions and Its Biomedical Applications: A Review

Deng, Jiu; Wei, Wenbo; Chen, Zongzheng; Lin, Baiquan; Zhao, Weijie; Luo, Yong; Zhang, Xiuli

doi:10.3390/mi10100676

Cited by 165 publications

(169 citation statements)

References 112 publications

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“…Therefore, the liver could offer a great potential for the integration of immune-cells-on-a-chip, since it is useful for studying the interactions between the drugs and the immune cells, as almost all drugs pass the liver and could accelerate drug development [ 85 ]. It would be ideal to study drug metabolism on a liver-on-a-chip device, specifically one which models the liver metabolism on a chip [ 86 , 87 ]. Moreover, the interactions of drugs with the immune system (and immune cells) should ideally be studied in a controlled in vitro environment.…”

Section: Integration Of Immune Cells and Components For Organs-on-mentioning

confidence: 99%

Immune Organs and Immune Cells on a Chip: An Overview of Biomedical Applications

et al. 2020

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Understanding the immune system is of great importance for the development of drugs and the design of medical implants. Traditionally, two-dimensional static cultures have been used to investigate the immune system in vitro, while animal models have been used to study the immune system’s function and behavior in vivo. However, these conventional models do not fully emulate the complexity of the human immune system or the human in vivo microenvironment. Consequently, many promising preclinical findings have not been reproduced in human clinical trials. Organ-on-a-chip platforms can provide a solution to bridge this gap by offering human micro-(patho)physiological systems in which the immune system can be studied. This review provides an overview of the existing immune-organs-on-a-chip platforms, with a special emphasis on interorgan communication. In addition, future challenges to develop a comprehensive immune system-on-chip model are discussed.

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Section: Integration Of Immune Cells and Components For Organs-on-mentioning

confidence: 99%

Immune Organs and Immune Cells on a Chip: An Overview of Biomedical Applications

et al. 2020

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“…Also, they permit deploying multiple parameters, including geometry of cell culture, controlling bloodstream, mass transfer, and cell-cell and cell-matrix interactions, all of which are essential in producing a 3D mimicking platform. 184,185 Mechanical and chemical consideration. Alginate has been a commonly used material in many studies throughout the last decades.…”

Section: Extracellular Matrixmentioning

confidence: 99%

Liver Tissue Engineering as an Emerging Alternative for Liver Disease Treatment

Mirdamadi

Kalhori

Zakeri

et al. 2020

Tissue Engineering Part B: Reviews

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Chronic liver diseases affect thousands of lives throughout the world every year. The shortage of liver donors for transplantation has been the main driving force to employ alternative methods such as liver tissue engineering (LTE) in fabricating a three-dimensional transplantable liver tissue or enhancing cell delivery techniques alleviating the need for liver donors. LTE consists of three components, cells, ECM (extracellular matrix), and signaling molecules, which we discuss the first and second. The three most common cell sources used in LTE are human and animal primary hepatocytes, and stem cells for different applications. Two major categories of ECM are used to mimic the microenvironment of these cells, named scaffolds and microbeads. Scaffolds have been made by numerous methods with a wide range of synthetic and natural biomaterials. Cell encapsulation has also been utilized by many polymeric biomaterials. To investigate their functions, many properties have been discussed in the literature, such as biochemical, geometrical, and mechanical properties, in both of these categories. Overall, LTE shows excellent potential in assisting hepatic disorders. However, some challenges exist that prevent the practical use of it clinically, making LTE an ongoing research subject in the scientific society.

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“…In spite of previous empirical and mathematical modeling efforts, the impact of parenchymal mechanics and flow on metastatic growth in the liver remains poorly understood, as is the biology regulating tumor-parenchyma interactions near the tumor boundary. And while emerging biomimetic platforms (e.g., [54,55]) can evaluate some of these dynamics, it remains difficult to resolve tumor foci at multicellular resolution over long times. Past multiscale modeling investigations have mainly focused on discrete or smaller-scale simulations, or worked to provide insights at larger, continuum scales.…”

Section: Prior Mathematical Modelingmentioning

confidence: 99%

Impact of tumor-parenchyma biomechanics on liver metastatic progression: a multi-model approach

Brodin

Nishii

Frieboes

et al. 2020

Preprint

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Colorectal carcinoma (CRC) and other cancers often metastasize to the liver in later stages of the disease, contributing significantly to patient death. While the biomechanical properties of the liver parenchyma (normal liver tissue) are known to affect primary and metastatic tumor growth in liver tissues, the role of these properties in driving or inhibiting metastatic inception remains poorly understood. This study uses a multi-model approach to study the effect of tumor-parenchyma biomechanical interactions on metastatic seeding and growth; the framework also allows investigating the impact of changing tissue biomechanics on tumor dormancy and "reawakening." We employ a detailed poroviscoelastic (PVE) model to study how tumor metastases deform the surrounding tissue, induce pressure increases, and alter interstitial fluid flow in and near the metastases. Results from these short-time simulations in detailed single hepatic lobules motivate constitutive relations and biological hypotheses for use in an agent-based model of metastatic seeding and growth in centimeter-scale tissue over months-long time scales. We find that biomechanical tumor-parenchyma interactions on shorter time scales (adhesion, repulsion, and elastic tissue deformation over minutes) and longer time scales (plastic tissue relaxation over hours) may play a key role in tumor cell seeding and growth within liver tissue. These interactions may arrest the growth of micrometastases in a dormant state and can prevent newly arriving cancer cells from establishing successful metastatic foci. Moreover, the simulations indicate ways in which dormant tumors can "reawaken" after changes in parenchymal tissue mechanical properties, as may arise during aging or following acute liver illness or injury. We conclude that the proposed modeling approach can yield insight into the role of tumor-parenchyma biomechanics in promoting liver metastatic growth, with the longer term goal of identifying conditions to clinically arrest and reverse the course of late-stage cancer. 4/25

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Engineered Liver-On-A-Chip Platform to Mimic Liver Functions and Its Biomedical Applications: A Review

Cited by 165 publications

References 112 publications

Immune Organs and Immune Cells on a Chip: An Overview of Biomedical Applications

Immune Organs and Immune Cells on a Chip: An Overview of Biomedical Applications

Liver Tissue Engineering as an Emerging Alternative for Liver Disease Treatment

Impact of tumor-parenchyma biomechanics on liver metastatic progression: a multi-model approach

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