Clog-free all-aqueous microfluidic fabrication of hydrogel microfibers governed by a universal scaling law

Abstract

Hydrogel microfibers provide a versatile platform for cell encapsulation and tissue engineering, but their fabrication typically involves harsh or clog-prone processes that limit cytocompatibility or scalability. Here, we report a clog-free, all-aqueous water-in-water-in-water microfluidic approach for continuous and cytocompatible fabrication of hydrogel microfibers. This approach uses immiscible aqueous polymer solutions to enable fiber formation and controlled crosslinking without organic solvents and rapid solidification, preventing channel clogging during continuous operation. Using alginate as a model biomaterial, we generate meter-long microfibers that can be spun into macroscopic films. Systematic experiments and laminar flow modeling reveal a universal scaling law, , showing that the fiber diameter D_f depends solely on the collection capillary diameter D_c and the ratio of inner flow rate Q_i to the total flow rate of the middle and outer phases Q_sum. Finally, we demonstrate encapsulation of pancreatic β-cells, which retain glucose-responsive insulin secretion comparable to that of unencapsulated cells. This work establishes the physical basis of all-aqueous microfiber fabrication and provides a robust, scalable, and cytocompatible approach for cell encapsulation.