Preparation of Controlled Multicompartmental Gel Microcarriers Based on Aqueous Two-Phase Emulsions for 3D Partitioned Cell Coculture In Vitro

A facile method was proposed for preparing controllable multicompartment gel microcarriers using an aqueous two-phase emulsion system. By leveraging the density difference between the upper polyethylene glycol solution and the lower dextran-calcium chloride (CaCl2) solution in the collection solution and the high viscosity of the lower solution, controllable fusion of core–shell droplets made by coextrusion devices was achieved at the water/water (w/w) interface to fabricate microcarriers with separated core compartments. By adjusting the sodium alginate concentration, collected solution composition, and number of fused liquid droplets, the pore size, shape, and number of compartments could be controlled. Caco-2 and HepG2 cells were encapsulated in different compartments to establish gut–liver coculture models, exhibiting higher viability and proliferation compared to monoculture models. Notably, significant differences in cytokine expression and functional proteins were observed between the coculture and monoculture models. This method provides new possibilities for preparing complex and functional three-dimensional coculture materials.