Flexible Generation of Multi‐Aqueous Core Hydrogel Capsules Using Microfluidic Aqueous Two‐Phase System

Abstract Hydrogel capsules are widely applied in materials science, pharmaceutical science, and tissue engineering due to their tunable nature, defined core–shell architecture, and proper biocompatibility. Specially, multi‐core capsules are highly functional carriers with notable advantages for co‐encapsulation of diverse incompatible components without cross‐contamination. However, current approaches for generating such capsules are limited by using gas/oil‐water‐oil systems, leading to poor biocompatibility and functions due to the gas/oil cores. Herein, a simple and new approach is proposed for flexible fabrication of multi‐aqueous core hydrogel capsules (MACHC) using microfluidic aqueous two‐phase system (µATPS). In this system, a flow‐focusing microfluidic device is designed to create a stable laminar flow with two immiscible liquids composed of polyethylene glycol and dextran, which is sheared by oil phase to further effectively produce MACHC. The volume and components of each core can be well tailored by precisely adjusting the distinct flows, while the number of cores is determined by the orifice design of microfluidic chip. The MACHC are successfully used to co‐encapsulate heterogeneous hepatic and endothelial cells, indicating good biocompatibility and multi‐functionality of the multi‐core carriers. The proposed µATPS‐based approach is stable and convenient, holding promise for generation of multi‐responsive materials, tissue engineering, and co‐delivery of diverse drugs.