Spatially controlled construction of assembloids using bioprinting

The biofabrication of three-dimensional (3D) tissues that recapitulate organ-specific architecture and function would benefit from temporal and spatial control of cell-cell interactions. Bioprinting, while potentially capable of achieving such control, is poorly suited to spheroids and organoids with conserved cytoarchitectures that are susceptible to plastic deformation. Here, we develop a platform, termed Spheroid Transfer Assisted by Magnetic Printing (STAMP), consisting of an iron-oxide nanoparticle laden hydrogel and magnetized 3D printer to enable the controlled lifting, transport, and deposition of spheroids and organoids. We identify cellulose nanofibers as both an ideal biomaterial for encasing organoids with magnetic nanoparticles and a shear-thinning, self-healing support hydrogel for maintaining the spatial positioning of organoids to facilitate the generation of assembloids. We leverage STAMP to create precisely arranged assembloids composed of human pluripotent stem cell derived neural organoids and patient-derived glioma organoids. In doing so, we demonstrate the potential for the STAMP platform to construct assembloids which recapitulate key developmental processes and disease etiologies.