Controllable Fabrication of Composite Core-Shell Capsules at a Macroscale as Organoid Biocarriers

The cell encapsulation technology is promising for generation of functional carriers with well-tailored structures for efficient transplantation and immunoprotection of cells/tissues. Stem cell organoids are highly potential for recapitulating the intricate architectures and functionalities of native organs and also providing an unlimited cell source for cellular replacement therapy. However, it remains challenging for loading the organoids with hundreds of micrometers size by current existing cell carriers. Herein, a simple and facile coextrusion strategy is developed for controllable fabrication of Ca-alginate/poly(ethylene imine) (Alg/PEI) macrocapsules for efficient encapsulation and cultivation of organoids. Human-induced pluripotent stem cell (hiPSC)-derived islet organoids are encapsulated in the aqueous compartments of the capsules and immunoisolated by a semipermeable Alg/PEI shell. Via electrostatic interactions, a PEI polyelectrolyte can be incorporated in the shell for restricting its swelling, thus effectively improving the stability of the capsules. The Alg/PEI macrocapsules are featured with desirable selective permeability for immunoisolation of antibodies from reaching the loaded organoids. Meanwhile, they also exhibit excellent permeability for mass transfer due to their well-defined core-shell structure. As such, the encapsulated islet organoids contain islet-specific multicellular components, with high viability and sensitive glucose-stimulated insulin secretion function. The proposed approach provides a versatile encapsulation system for tissue engineering and regenerative medicine applications.