On-Chip Fabrication and Control of Compartmentalized Hydrogel Microcapsules

Hydrogel capsules have emerged as transformative platforms in biomedicine and materials engineering, leveraging their tunable physicochemical properties, core-shell architectural precision, and cytocompatibility for applications ranging from targeted drug delivery to 3D tissue modeling. Among these, multicompartmental capsules stand out as high-efficiency carriers, enabling co-encapsulation of incompatible therapeutics (e.g., hydrophilic/hydrophobic drugs, antagonistic enzymes) within isolated aqueous domains. Herein, we successfully achieve the flexible fabrication of compartmentalized hydrogel capsules (CHCs) using a 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 dextran and polyethylene glycol, which is sheared by oil phase to further effectively produce CHCs. 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 the microfluidic chip. These results demonstrate that the μATPS platform and CHCs hold promising potential for applications in multi-responsive material engineering, tissue regeneration, and cooperative drug delivery systems.