Herein, we demonstrate a novel method for the generation of monodisperse cell-like structures containing a biocompatible hydrogel matrix surrounded by a membrane responsive to chemical cues. Specifically, we employ droplet-based microfluidics to generate PEG-PLA polymersomes encapsulating alginate in liquid form. We investigate alginate core gelation by creating an osmotic pressure gradient across the polymeric membrane that, through expansion, allows the passage of calcium ions. The effects of calcium concentration on the core gelation are explored.