Spatially controlled construction of assembloids using bioprinting

Julien G. Roth, Lucia G. Brunel, Michelle S. Huang, Yueming Liu, Betty Cai, Sauradeep Sinha, Fan Yang, Sergiu P. Pașca, Sungchul Shin and Sarah C. Heilshorn ()
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Julien G. Roth: Stanford University School of Medicine
Lucia G. Brunel: Stanford University
Michelle S. Huang: Stanford University
Yueming Liu: Stanford University
Betty Cai: Stanford University
Sauradeep Sinha: Stanford University
Fan Yang: Stanford University
Sergiu P. Pașca: Stanford University
Sungchul Shin: Stanford University
Sarah C. Heilshorn: Stanford University

Nature Communications, 2023, vol. 14, issue 1, 1-14

Abstract: Abstract 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 organoids with conserved cytoarchitectures that are susceptible to plastic deformation. Here, we develop a platform, termed Spatially Patterned Organoid Transfer (SPOT), consisting of an iron-oxide nanoparticle laden hydrogel and magnetized 3D printer to enable the controlled lifting, transport, and deposition of 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 SPOT 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 SPOT platform to construct assembloids which recapitulate key developmental processes and disease etiologies.

Date: 2023
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DOI: 10.1038/s41467-023-40006-5

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