Abstract

Biofabrication of Tissue Assembloids

Yan Yan Shery Huang, University Lecturer in Bioengineering, University of Cambridge

Engineered assembly of multicellular materials, such as spheroids and organoids, represents a biomimetic process fundamental to tissue engineering and in vitro tissue modelling. Organization and fusion of different types of cellular building blocks can be harnessed to improve tissue maturation, and further, to achieve designable three-dimensional (3D) tissue architecture. Here, we illustrate diverse biofabrication strategies to create tissue ‘assembloids’. In the first example, a robust organoid engineering approach, Multi-Organoid Patterning and Fusion (MOrPF), is presented to assemble individual airway organoids of different sizes into upscaled, scaffold-free airway tubes with predefined shapes. Multi-Organoid Aggregates (MOAs) undergo accelerated fusion in a matrix-depleted, free-floating environment, possess a continuous lumen, and maintain prescribed shapes without an exogenous scaffold interface. By generating large, shape-controllable organ tubes, MOrPF enables upscaled organoid engineering towards integrated organoid devices and structurally complex organ tubes. In the second example, we demonstrate a deployable bioprinting strategy which can reconstruct compartmental tumoroids with cancer-associated fibroblasts (CAFs). The 3D printed core–shell tumoroids showed de novo synthesized extracellular matrices, and enhanced cellular proliferation compared to the tumour alone 3D printed spheroid culture. Further, the in vivo phenotypes of CAFs normally lost after conventional 2D co-culture re-emerged in the bioprinted model. Embedding the 3D printed tumoroids in an immune cell-laden collagen matrix permitted tracking of the interaction between immune cells and tumoroids, and subsequent simulated immunotherapy treatments. Overall, emerging development in biofabrication could significantly widen the applications of ‘assembloids’ for replicating cross-length scale tissue architectures towards in vitro models which integrate biology, physiology and anatomy.