Microfluidic Generation of Core-Shell Microgels as a Versatile Cell-Culture Platform

Abstract

Microfabrication technology provides a versatile platform for engineering hydrogels used in biomedical applications with high-resolution control and injectability. Herein, we present a strategy of fabricating core-shell microgel structures for applications as in vitro cell culture platform and injectable tissue constructs, by combining (1) microfluidics-assisted fabrication of microgels, and (2) providing silica hydrogel layer on the microgel surface. A flow-focusing microfluidic device was utilized to generate droplets containing photocrosslinkable methacrylated gelatin, followed by exposure to UB fabricate gelatin microgels. The size of the microgels could be easily controlled by varying the ratio of flow rates of aqueous and oil phases in the microfluidic device. The microgels were used as in vitro cell culture platform to grow cardiac cells on the microgel surface: The cells readily adhered on the microgel surface and proliferated over time while maintaining high viability (>90%). The cells on the microgels were also able to migrate to their surrounding area. In addition, the microgels eventually degraded over time. These results demonstrate that cell-seeded microgels have a great potential as injectable tissue constructs. Furthermore, we demonstrated that coating the cells on microgels with biocompatible, biodegradable silica hydrogels via sol–gel method provided significant protection against oxidative stress which is often encountered during injection into host tissues and detrimental to the cells. Overall, the microfluidic approach to generate cell-adhesive microgel core, coupled with silica hydrogels as a protective shell, will be highly useful as a cell culture platform to generate a wide range of injectable tissue constructs.