Functional Integration of Synthetic Cells into 3D Microfluidic Devices for Artificial Organ-on-Chip Technologies.

Microfluidics play a pivotal role in organ-on-chip technologies and in the study of synthetic cells, especially in the development and analysis of artificial cell models. However, approaches that use synthetic cells as integral functional components for microfluidic systems to shape the microenvironment of natural living cells cultured on-chip have not been explored. Here, we integrate colloidosome-based synthetic cells into 3D microfluidic devices, pioneering the concept of synthetic cell-based microenvironments for organs-on-chip. We devise methods to create dense and stable networks of silica colloidosomes, enveloped by supported lipid bilayers, within microfluidic channels. These networks promote receptor-ligand interactions with on-chip cultured cells. Furthermore, we introduce a technique for the controlled release of growth factors from the synthetic cells into the channels, using a calcium alginate-based hydrogel formation within the colloidosomes. To demonstrate the potential of the technology, we present a modular plug-and-play lymph-node-on-a-chip prototype that guides the expansion of primary human T cells by stimulating receptor ligands on the T cells and modulating their cytokine environment. This integration of synthetic cells into microfluidic systems offers a new direction for organ-on-chip technologies and suggests further avenues for exploration in potential therapeutic applications. This article is protected by copyright. All rights reserved.