Abstract
Cell-laden hydrogel microcarriers are widely used in diverse biomedical applications like three-dimensional (3D) cell culture, cellular therapy, and tissue engineering, where microcarriers were generally produced by oil, which is the common but not optimal choice, as oil may cause cytotoxicity or protein denaturation. Here, an all-aqueous-phase microfluidics is presented to achieve oil-free emulsification of cell-laden microcapsules and 3D cell culture. Aqueous solutions with different concentration gradients are used as an immiscible continuous phase and a dispersed phase, and oscillation from a solenoid valve facilitates the formation of microcapsules at the water-water interface. By adjusting aqueous-phase flow rates and oscillating frequencies, core-shell microcapsules with controllable structures can be stably and continuously generated. In further 3D cell culture, encapsulated cells maintained good viabilities and aggregated together. These features show that the oil-free microfluidic method may have broad prospects in many biomedical applications.