Deployable extrusion bioprinting of compartmental tumoroids with cancer associated fibroblasts for immune cell interactions

Abstract

Realizing the translational impacts of three-dimensional (3D) bioprinting for cancer research necessitates innovation in bioprinting workflows which integrate affordability, user-friendliness, and biological relevance. Herein, we demonstrate ‘BioArm’, a simple, yet highly effective extrusion bioprinting platform, which can be folded into a carry-on pack, and rapidly deployed between bio-facilities. BioArm enabled the reconstruction of compartmental tumoroids with cancer-associated fibroblasts (CAFs), forming the shell of each tumoroid. 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. Our deployable extrusion bioprinting workflow could significantly widen the accessibility of 3D bioprinting for replicating multi-compartmental architectures of tumour microenvironment, and for developing strategies in cancer drug testing in the future.