Multi-Compartment 3D-Cultured Organ-on-a-Chip: Towards a Biomimetic Lymph Node for Drug Development
Aya Shanti,
Bisan Samara,
Amal Abdullah,
Nicholas Hallfors,
Dino Accoto,
Jiranuwat Sapudom,
Aseel Alatoom,
Jeremy Teo,
Serena Danti,
Cesare Stefanini
Affiliations
Aya Shanti
Healthcare Engineering Innovation Center, Biomedical Engineering Department, Khalifa University of Science and Technology, Abu Dhabi P.O. Box 127788, UAE
Bisan Samara
Healthcare Engineering Innovation Center, Biomedical Engineering Department, Khalifa University of Science and Technology, Abu Dhabi P.O. Box 127788, UAE
Amal Abdullah
Healthcare Engineering Innovation Center, Biomedical Engineering Department, Khalifa University of Science and Technology, Abu Dhabi P.O. Box 127788, UAE
Nicholas Hallfors
Healthcare Engineering Innovation Center, Biomedical Engineering Department, Khalifa University of Science and Technology, Abu Dhabi P.O. Box 127788, UAE
Dino Accoto
School of Mechanical & Aerospace Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798, Singapore
Jiranuwat Sapudom
Division of Engineering, New York University Abu Dhabi, Abu Dhabi P.O. Box 129188, UAE
Aseel Alatoom
Division of Engineering, New York University Abu Dhabi, Abu Dhabi P.O. Box 129188, UAE
Jeremy Teo
Division of Engineering, New York University Abu Dhabi, Abu Dhabi P.O. Box 129188, UAE
Serena Danti
Department of Civil and Industrial Engineering, University of Pisa, 56122 Pisa, Italy
Cesare Stefanini
Healthcare Engineering Innovation Center, Biomedical Engineering Department, Khalifa University of Science and Technology, Abu Dhabi P.O. Box 127788, UAE
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.
