Design and Fabrication of Microfluidic-Based 3D Microphysiological Systems for Studying Cell Migration and Invasion Behaviors

Abstract

The cell migration and invasion behaviors play pivotal roles in tissue regeneration. For the skin repair process, a directed inflammatory response that regulates fibroblasts is critical for efficient wound healing. In this study, the authors present the design and fabrication of a microfluidic-based three-dimensional (3D) microphysiological system and how it impacts in controlling fibroblast migration and invasion under the induction of differently polarized macrophages. The microfluidic device had two chambers on opposite sides of a 1 mm micochannel, providing directed induction and sufficient width for long-term observation. The test cells could be seeded with or without matrix gel, cultured in a 2D or 3D microenvironment according to experiment settings. The microchannel allowed for any sorts of matrix filling and was on-demanding for continuous surveillance. Herein, our microfluidic device reserved the advantages of traditional methods using transwell chamber or scratch wound healing assay. In addition, it even came with more superiority such as retrievability, dynamic observation, and 3D environment simulation. The migration and invasion pattern of NIH3T3 modulated by RAW264.7 macrophages in different polarization status was demonstrated as an example. The results of the migration assay corresponded with that of the proliferation and gene expression experiments, verifying that our device was fully capable of restoring in vivo microenvironment and presenting cellular motility behaviors.