Monolithic microfluidic platform for exerting gradients of compression on cell-laden hydrogels, and application to a model of the articular cartilage

doi:10.1016/j.snb.2020.127917

Sensors and Actuators B: Chemical

Volume 315, 15 July 2020, 127917

https://doi.org/10.1016/j.snb.2020.127917 Get rights and content

Under a Creative Commons license

open access

Highlights

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Monolithic device with a vertical membrane for mechanical stimulation of tissues.
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Actuation unit with 3 individual chambers to apply negative and/or positive pressure.
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Real-time tissue imaging at the single cell level: monitoring cell deformation.
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Application of healthy and hyper-physiological compressions to a cartilage model.
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Possible generation of combinations of compression and bulk shear.

Abstract

Movement is essential to our quality of life, and regulates cell behavior via mechanical stimulation. Here, we report a monolithic microfluidic platform, in which engineered tissues composed of cells in a hydrogel are exposed to gradients of mechanical compression. Mechanical stimulation is applied through the deflection of a thin polydimethylsiloxane (PDMS) vertical membrane. The device design and all actuation parameters were optimized in this work to produce physiologically relevant compression on a cartilage model (strain of 5–12 %), as well as gradients of compression ranging from healthy to hyper-physiological conditions in the same device, as evidenced by the measured gradients in cell deformation. While this work focuses on mechanical compression of engineered tissues, we also demonstrated that our platform allowed creating more sophisticated multi-modal stimulation patterns. As the membrane is actuated by three independently addressed yet connected pressurized chambers, a variety of programmable deflection patterns and various cell stimulation modalities can easily be created by tuning the pressure applied in the different chambers (positive vs. negative, and amplitude). Advantageously, the fabrication of this monolithic platform is straightforward, with a single-step process. Moreover, the vertical membrane configuration allows for real-time imaging of cells encapsulated in the hydrogel matrix. The herein reported platform is highly versatile and of great interest to model other types of tissues, which also experience complex mechanical actuation patterns in vivo.

Keywords

Microfluidics

Mechanical actuation

Polydimethylsiloxane

Cartilage

Cell-laden hydrogel

Cited by (0)

Carlo Alberto Paggi received his M.S. degree from University of Twente, The Netherlands,in 2018. He is currently doing his Ph.D. at University of Twente. In his Ph.D., he particularly focuses on organ-on-chip devices, microfluidics, and cell biology. He is particularly focused on articular cartilage and osteoarthritis progression.

Bastien Venzac received his Ph.D. degree from the Curie Institute and Pierre et Marie Curie University (Paris, France), in the group of Jean-Louis Viovy and Stephanie Descroix in 2016. His post-doc research focuses on organ-on-chip technology and the development of simple microfluidic technology for biological applications.

Marcel Karperien obtained his Ph.D. at the Netherlands Institute for Developmental Biology and Stem Cell Research. Currently, he is full professor and head of the Department of Developmental BioEngineering group at University of Twente. He is interested in developing new solutions for treating cartilage related disorders. His work is technology inspired and is characterized by a multidisciplinary approach integrating typical engineering disciplines with life-sciences.

Jeroen Leijten received his Ph.D. degree from Twente University in 2012. Currently, he is appointed as an associate professor at Twente University, The Netherlands. His research focuses on the development and application of microtechnological platforms including droplet generators, smart instructive micromaterials, single cell microgels, 3D cellular organoids, 3D printing, and organ-on-chips.

Séverine Le Gac received her Ph.D. degree cum laude from the University of Lille, France, in 2004. She is Professor at the University of Twente, The Netherlands, leading the Applied Microfluidics for BioEngineering Research (AMBER) team. Her research focuses on the use of miniaturized devices for biological and medical applications, and in particular for cancer research and the field of assisted reproductive technologies.

¹: These authors contributed equally to this work.