Controlled assembly of heterotypic cells in a core–shell scaffold: organ in a droplet

Abstract

This paper reports a droplet-based microfluidics approach to fabricate a large number of monodisperse, portable microtissues, each in an individual drop. We use water-water-oil double emulsions as templates and spatially assemble hepatocytes in the core and fibroblasts in the shell, forming a 3D liver model in a drop.

Development of an in vitro human liver system for interrogating nonalcoholic steatohepatitis

“…Various chip-based models have attempted to recreate a physiologically relevant liver sinusoidal microenvironment by adopting approaches designed to generate three-dimensional (3D) aggregates or spheroids, micropatterning and bioprinting liver cell types into specific spatial configurations and some introducing fluid flow via microfluidics (38)(39)(40)(41)(42). For our lipotoxic system, we chose to use a larger-scale 3D system (7,8) that utilizes more cells, which enables simultaneous collection of multiple endpoints (e.g., transcriptomics, lipidomics, and imaging) from the same experiment, allowing for interassay comparison within a single experiment.…”

Versatile, cell and chip friendly method to gel alginate in microfluidic devices

“…To release the chelated Ca 2+ , an acidified carrier fluid is typically applied to decrease the pH through the diffusion of H + from the continuous to the dispersed phase resulting in subsequent internal gelation of the alginate. 29,38,41,[44][45][46] While effective in achieving a slower and more homogeneous gelation process that does not clog microfluidic channels immediately and results in well dispersed microparticles, unfortunately all of these approaches are reliant on a pH drop well below the physiological range and are therefore detrimental to cell viability. A recent study 29 showed that cell viability can somewhat be enhanced if the cell-loaded gels are rinsed from the acidic environment shortly after gelation, however, even after short time scales (~2min), the survival rate of the encapsulated cells showed a decrease to ~80% and to ~0% after 30 min between encapsulation, gelation and resuspension in cell medium.…”

Applications of Microfluidics in Quantitative Biology

“…[102] Another application of droplet-based microfluidics were found in tissue engineering and regenerative medicines, where researchers designed and fabricated organ-like three-dimensional structures to simulate the organ functions. [103] The threedimensional micro-environment construction provides an alternative between conventional two-dimensional methods and animal models that are normally costly and unreproducible. The He group reported the generation of biomimetic ovarian micro-tissue through microfluidics by using both harder (alginate) and softer (collagen) materials.…”