Natural-derived polymers are used to coat liquid-core capsules layer by layer to encapsulate cells. Human osteoblast-like cells (SaOs-2) are encapsulated in such spherical devices using a three-step methodology: i) ionotropic gelation to produce alginate beads encapsulating the cells; ii) layer-by-layer coating using water-soluble chitosan and alginate; and iii) core liquefaction. Cells remain viable for 3 d after the encapsulation procedure, suggesting that the developed capsules possess a semipermeable, nanostructured coating. All of the capsules exhibit a spherical shape, smooth surface and liquid-core characteristics. All of the processes are conducted under mild conditions and physiological pH. We consider that the methodology employed in the development of the capsules obtained from natural-based biomaterials has potential to find applicability in the development of scaffolds or cell carriers in tissue engineering and regenerative medicine.