Generation of Orthogonal Gradients of the Matrix Stiffness and Chemotactic Cues in a Suspended Array of Hydrogel to Study hMSCs Migration.

ACS Sens

Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut 06511,United States.

Published: February 2025

Stem cell migration is a tightly regulated process in vivo, orchestrated by a collection of mechanical and chemotactic cues via concentration gradients. A variety of in vitro assays have been developed to facilitate cell migration studies; however, very few assays allow the investigation of both matrix stiffness and chemotactic cues on cell migration within a single device, especially in a three-dimensional (3D) environment. Here, we develop a microfluidic device that can produce 3D orthogonal gradients of matrix stiffness and chemotactic cues with varied steepness in a suspended array of hydrogel cylinders. The device's working principle is the formation of diffusion-driven concentration gradients within a suspended array of hydrogel cylinders between a source and a sink. Device fabrication is based on poly(dimethylsiloxane) (PDMS) replica molding, followed by assembly on a glass substrate. To validate this device, we study the migration of human mesenchymal stem cells (hMSCs) in response to orthogonal gradients of matrix stiffness and stromal cell-derived factor 1 alpha (SDF-1α). This technology has the potential to be applied to various cell types, facilitating exploration in different cellular contexts.

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http://dx.doi.org/10.1021/acssensors.4c02793DOI Listing

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