Microfluidics‐Assisted Fabrication of Microtissues with Tunable Physical Properties for Developing an In Vitro Multiplex Tissue Model

Abstract

Herein, a new 3D hydrogel-based co-culture tissue model is developed to systematically examine the effect of mutual influence between two different cell types residing in separated but interactive zones. Microtissues containing macrophage as a model cell type are first developed by photocrosslinking cell-laden droplets containing methacrylic gelatin (MGel), using a microfluidic flow-focusing device. Regardless of the material conditions, the cell viability is well maintained demonstrating the biocompatibility of the fabrication process as well as the 3D microenvironment provided by the microgels. More significantly, it is shown that the proliferation and lipopolysaccharide (LPS)-induced differentiation (‘Mϕ polarization’) of macrophages are heavily influenced by the mechanical properties of the microgels, controlled with MGel concentrations. Eventually, these macrophage microtissues are embedded into a larger tissue construct, containing either normal or cancer cells, to develop a co-culture tissue model to study the mutual effects between macrophage in different stages of differentiation and the surrounding cells. It is expected that this “multiplex” tissue model would allow an effective platform for monitoring of complex interactions between two different cell types cells residing in adjacent, compartmentalized areas within a 3D tissue environment.