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Open AccessArticle

Multi-Compartment 3D-Cultured Organ-on-a-Chip: Towards a Biomimetic Lymph Node for Drug Development

Healthcare Engineering Innovation Center, Biomedical Engineering Department, Khalifa University of Science and Technology, Abu Dhabi P.O. Box 127788, UAE
School of Mechanical & Aerospace Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798, Singapore
Division of Engineering, New York University Abu Dhabi, Abu Dhabi P.O. Box 129188, UAE
Department of Biomedical and Mechanical Engineering, New York University, P.O. Box 903, New York, NY 10276-0903, USA
Department of Civil and Industrial Engineering, University of Pisa, 56122 Pisa, Italy
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Pharmaceutics 2020, 12(5), 464;
Received: 20 March 2020 / Revised: 23 April 2020 / Accepted: 30 April 2020 / Published: 19 May 2020
(This article belongs to the Special Issue Microfluidics as a Tool for Drug Delivery)
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. View Full-Text
Keywords: biomimicry; drug development; lymph node; microfabrication; microfluidics; organ-on-a-chip biomimicry; drug development; lymph node; microfabrication; microfluidics; organ-on-a-chip
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Shanti, A.; Samara, B.; Abdullah, A.; Hallfors, N.; Accoto, D.; Sapudom, J.; Alatoom, A.; Teo, J.; Danti, S.; Stefanini, C. Multi-Compartment 3D-Cultured Organ-on-a-Chip: Towards a Biomimetic Lymph Node for Drug Development. Pharmaceutics 2020, 12, 464.

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