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 tumor 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 tumor microenvironment, and for developing strategies in cancer drug testing in the future.

Soft Hydrogel Shapeability via Supportive Bath Matching in Embedded 3D Printing

“…A self‐designed custom‐made 3D extrusion‐based printer was used for all the printing experiments. [ 40,41 ] The 3D STL files of the printed structures were either custom‐designed or downloaded from Thingiverse (http://www.thingiverse.com) (“All Alphabet Letters” by 6brueder). The ink was drawn into a 1 mL syringe, and the syringe was loaded to the syringe holder of the setup.…”

Artificial tumor matrices and bioengineered tools for tumoroid generation

“…3D-printed CAFs tumoroids were seeded in a collagen matrix containing immune cells, which could allow the interaction between immune cells and tumoroids to be tracked in the 3D environment [177]. Highly drug-resistant MCTs-ECM tumor grafts were analyzed in a 3D in vitro model by combining MCTs and collagen matrix.…”

3D bioprinting complex models of cancer

“…However, the technique's success is dependent on the physical properties of the bioink, such as viscosity and surface tension, which may limit the range of biomaterials that can be used. 65 This approach has been effectively used to print uniform drops containing human breast cancer cellular spheroids into concave wells, providing a way to generate models for bio-imaging during cancer studies. 37 Additionally, this technique can be used to print highly complex combinations of biomaterials such as hydroxyapatite, 66 polyethyleneimine (PEI), and riboflavin sodium phosphate (HE) to create more realistic and informative cancer models.…”

“…63 By utilizing extrusion bioprinters to deposit cells in the creation of compartmental tumoroids, Mazzaglia and Sheng closely mimicked the in vivo tumor environment. 65 When combined with a collagen matrix rich in immune cells, this allows for the Biomaterials Science Review study of the interactions between the immune cells and the tumoroids, providing valuable insights into the mechanistic understanding of stromal cancer interactions as well as future drug testing approaches. In addition, these models can mimic different tumor stages and study the role of specific biomolecules and cell lines under controlled conditions.…”