Microfluidics-assisted fabrication of macrophage microtissues with tunable physical properties for developing in vitro multiplex tissue model

Microfluidic flow-focusing devices (FFD) are widely used to develop micron-scale emulsion particles ('droplets') with variable size and shape for biomedical applications. Specifically, droplets consisting of gel-forming polymers can be crosslinked to form microgels for tissue engineering and drug delivery. In this study, cell-encapsulated microgels fabricated by photocrosslinking droplets containing methacrylic gelatin (MGel). The mechanical properties of the microgels could be controlled by the MGel concentrations, while their size could be controlled by varying the flow rates during droplet generation. The viability of macrophages encapsulated in the microgels was well maintained regardless of the physical properties, while their proliferation was dependent on the mechanical properties. More significantly, lipopolysaccharide (LPS) induced M1/M2 differentiation of macrophages was also heavily influenced by the mechanical properties of the microgels. Eventually, these macrophage microtissues were embedded in a hepatocarcinoma tissue constructs as an in vitro tumor model to study the effects of macrophage in different stages of differentiation and mechanical environment on the surrounding cancer cells