Multi-compartment 3D-cultured organ-on-a-chip : towards a biomimetic Lymph Node for drug development

The interaction of immune cells with drugs and/or with other cell types should be mechanistically investigated in order to reduce attrition of new drug development. However, they are currently only limited technologies that address this need. In our work, we developed initial but significant buildin...

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Main Authors: Shanti, Aya, Samara, Bisan, Amal Abdullah, Hallfors, Nicholas, Accoto, Dino, Sapudom, Jiranuwat, Alatoom, Aseel, Teo, Jeremy, Danti, Serena, Stefanini, Cesare
Other Authors: School of Mechanical and Aerospace Engineering
Format: Article
Language:English
Published: 2021
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Online Access:https://hdl.handle.net/10356/148594
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Institution: Nanyang Technological University
Language: English
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spelling sg-ntu-dr.10356-1485942021-05-10T04:32:13Z Multi-compartment 3D-cultured organ-on-a-chip : towards a biomimetic Lymph Node for drug development Shanti, Aya Samara, Bisan Amal Abdullah Hallfors, Nicholas Accoto, Dino Sapudom, Jiranuwat Alatoom, Aseel Teo, Jeremy Danti, Serena Stefanini, Cesare School of Mechanical and Aerospace Engineering Engineering::Mechanical engineering Biomimicry Drug Development The interaction of immune cells with drugs and/or with other cell types should be mechanistically investigated in order to reduce attrition of new drug development. However, they are currently only limited technologies that address this need. In our work, we developed initial but significant building blocks that enable such immune-drug studies. We developed a novel microfluidic platform replicating the Lymph Node (LN) microenvironment called LN-on-a-chip, starting from design all the way to microfabrication, characterization and validation in terms of architectural features, fluidics, cytocompatibility, and usability. To prove the biomimetics of this microenvironment, we inserted different immune cell types in a microfluidic device, which showed an in-vivo-like spatial distribution. We demonstrated that the developed LN-on-a-chip incorporates key features of the native human LN, namely, (i) similarity in extracellular matrix composition, morphology, porosity, stiffness, and permeability, (ii) compartmentalization of immune cells within distinct structural domains, (iii) replication of the lymphatic fluid flow pattern, (iv) viability of encapsulated cells in collagen over the typical timeframe of immunotoxicity experiments, and (v) interaction among different cell types across chamber boundaries. Further studies with this platform may assess the immune cell function as a step forward to disclose the effects of pharmaceutics to downstream immunology in more physiologically relevant microenvironments. Published version 2021-05-10T04:32:13Z 2021-05-10T04:32:13Z 2020 Journal Article Shanti, A., Samara, B., Amal Abdullah, Hallfors, N., Accoto, D., Sapudom, J., Alatoom, A., Teo, J., Danti, S. & Stefanini, C. (2020). Multi-compartment 3D-cultured organ-on-a-chip : towards a biomimetic Lymph Node for drug development. Pharmaceutics, 12(5). https://dx.doi.org/10.3390/pharmaceutics12050464 1999-4923 https://hdl.handle.net/10356/148594 10.3390/pharmaceutics12050464 32438634 2-s2.0-85085387422 5 12 en Pharmaceutics © 2020 The Author(s). Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Engineering::Mechanical engineering
Biomimicry
Drug Development
spellingShingle Engineering::Mechanical engineering
Biomimicry
Drug Development
Shanti, Aya
Samara, Bisan
Amal Abdullah
Hallfors, Nicholas
Accoto, Dino
Sapudom, Jiranuwat
Alatoom, Aseel
Teo, Jeremy
Danti, Serena
Stefanini, Cesare
Multi-compartment 3D-cultured organ-on-a-chip : towards a biomimetic Lymph Node for drug development
description The interaction of immune cells with drugs and/or with other cell types should be mechanistically investigated in order to reduce attrition of new drug development. However, they are currently only limited technologies that address this need. In our work, we developed initial but significant building blocks that enable such immune-drug studies. We developed a novel microfluidic platform replicating the Lymph Node (LN) microenvironment called LN-on-a-chip, starting from design all the way to microfabrication, characterization and validation in terms of architectural features, fluidics, cytocompatibility, and usability. To prove the biomimetics of this microenvironment, we inserted different immune cell types in a microfluidic device, which showed an in-vivo-like spatial distribution. We demonstrated that the developed LN-on-a-chip incorporates key features of the native human LN, namely, (i) similarity in extracellular matrix composition, morphology, porosity, stiffness, and permeability, (ii) compartmentalization of immune cells within distinct structural domains, (iii) replication of the lymphatic fluid flow pattern, (iv) viability of encapsulated cells in collagen over the typical timeframe of immunotoxicity experiments, and (v) interaction among different cell types across chamber boundaries. Further studies with this platform may assess the immune cell function as a step forward to disclose the effects of pharmaceutics to downstream immunology in more physiologically relevant microenvironments.
author2 School of Mechanical and Aerospace Engineering
author_facet School of Mechanical and Aerospace Engineering
Shanti, Aya
Samara, Bisan
Amal Abdullah
Hallfors, Nicholas
Accoto, Dino
Sapudom, Jiranuwat
Alatoom, Aseel
Teo, Jeremy
Danti, Serena
Stefanini, Cesare
format Article
author Shanti, Aya
Samara, Bisan
Amal Abdullah
Hallfors, Nicholas
Accoto, Dino
Sapudom, Jiranuwat
Alatoom, Aseel
Teo, Jeremy
Danti, Serena
Stefanini, Cesare
author_sort Shanti, Aya
title Multi-compartment 3D-cultured organ-on-a-chip : towards a biomimetic Lymph Node for drug development
title_short Multi-compartment 3D-cultured organ-on-a-chip : towards a biomimetic Lymph Node for drug development
title_full Multi-compartment 3D-cultured organ-on-a-chip : towards a biomimetic Lymph Node for drug development
title_fullStr Multi-compartment 3D-cultured organ-on-a-chip : towards a biomimetic Lymph Node for drug development
title_full_unstemmed Multi-compartment 3D-cultured organ-on-a-chip : towards a biomimetic Lymph Node for drug development
title_sort multi-compartment 3d-cultured organ-on-a-chip : towards a biomimetic lymph node for drug development
publishDate 2021
url https://hdl.handle.net/10356/148594
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