Spatially controlled construction of assembloids using bioprinting

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.

Tumour organoids and assembloids: Patient‐derived cancer avatars for immunotherapy

“…Similarly, assembloid technology has found applications in normal tissues, including the brain 44 and the gastrointestinal tract, 40 as well as cancers, such as bladder cancer 37 and small‐cell lung cancer 45 . Many bioengineering tools have been proposed to facilitate assembloid fabrications, such as human brain assembloids using microfluidics, 44 and spatially constructing glioma organoids using 3D bioprinting 46 . Although the assembloid approaches differ from the organoid techniques, the ultimate goal is the same for clinical uses.…”

Organoid bioinks: construction and application

“…In addition, bioprinting allows for the precise spatial control of organoid assembly, promoting the formation of complex assembloids. Sarah Roth et al [141] developed a Spatially Patterned Organoid Transfer method, enabling the accurate spatial positioning of organoid building blocks. This approach involves using cellulose nanofiber hydrogel organoid bioink loaded with magnetic nanoparticles, which are then printed at specific spatial locations using a magnetized printer.…”

Advances and Challenges in Cerebral Organoids Research

“…We believe that innovative design, cutting-edge manufacturing techniques, and new technologies will facilitate the development and clinical applications of cerebral organoids. [125] Copyright 2023, Springer Nature.…”

“…D) A ventral forebrain region cerebral organoid assembled with a dorsal forebrain region cerebral organoid with cell migration. Reproduced with permission [125]. Copyright 2023, Springer Nature.…”