Microfluidic Templated Multicompartment Microgels for 3D Encapsulation and Pairing of Single Cells

Abstract

Controlled encapsulation and pairing of single cells within a confined 3D matrix can enable the replication of the highly ordered cellular structure of human tissues. Microgels with independently controlled compartments that can encapsulate cells within separately confined hydrogel matrices would provide precise control over the route of pairing single cells. Here, a one-step microfluidic method is presented to generate monodisperse multicompartment microgels that can be used as a 3D matrix to pair single cells in a highly biocompatible manner. A method is presented to induce microgels formation on chip, followed by direct extraction of the microgels from oil phase, thereby avoiding prolonged exposure of the microgels to the oil. It is further demonstrated that by entrapping stem cells with niche cells within separate but adjacent compartments of the microgels, it can create complex stem cell niche microenvironments in a controlled manner, which can serve as a useful tool for the study of cell-cell interactions. This microfluidic technique represents a significant step toward high-throughput single cells encapsulation and pairing for the study of intercellular communications at single cell level, which is of significant importance for cell biology, stem cell therapy, and tissue engineering.

Designing Microgels for Cell Culture and Controlled Assembly of Tissue Microenvironments

“…A wide variety of fabrication techniques (e.g., suspension and emulsion polymerizations, [23,42,43] precipitation polymerization, [44] microfluidics, [45,46] electrospraying [47,48] ) also exist for processing polymers into microgels ( Figure 2C). The microgel chemistry is typically selected for ease of fabrication, functionalization, and compatibility with the fabrication process.…”

The Construction and Application of Three‐Dimensional Biomaterials

“…Zhao et al developed a kind of NIR light‐sensitive microcarriers to encapsulate cells inside their macropores and release them on demand by irradiating with NIR light . Based on the single emulsion template, multi‐compartmental microcarriers are also achievable by simply upgrading the dispersed phase channel with multiple parallel channels, which is similar to that in the electro‐jetting procedure. In addition to the multi‐compartmental ones, core‐shell structured microcarriers are also accessible from double‐emulsion droplet templates, which is formed on the basis of the generated single‐emulsion droplets by secondary emulsification of the mixed fluid.…”

Biopolymer Microparticles Prepared by Microfluidics for Biomedical Applications

“…Microfluidics also enables compartmentalization and physical separation of multiple cells within single MPs. Multiple single cells, for example, have been encapsulated in distinct compartments of Ca‐alginate Janus MPs, which were prepared through the rapid on‐chip gelation of W/O emulsion droplets composed of multiple aqueous phases and immediate transfer of the microgels into an aqueous buffer . Encapsulation of single MSCs and single HUVECs in the Janus MPs led to the osteogenesis of MSCs through the cell–cell interactions between the two cells.…”