Jammed Foamed Microgel-based Bioprinting for Ex Vivo Reconstruction of 3D T Cell-Cancer Cell Interactions.

Abstract

T cells in solid tumors migrate through the tumor tissues to find cancer cells and eliminate them. Ex vivo reconstruction of T cell-cancer cell interactions is key for the rational design of cancer immunotherapy. Porous 3D structures essential for optimal T cell motility are challenging to fabricate by 3D printing using conventional bioinks: at high ink concentration, rheological properties are suitable for printing, but T cells are trapped in dense polymer networks, and vice versa. To overcome this limitation, a new bioink based on foamed microgels (FMGs) that facilitates T cell motility is devised, without compromising printability in extrusion 3D printing. Norbornene-functionalized gelatin is synthesized, foamed, cross-linked, and ground to generate FMGs. The FMGs exhibited rougher surfaces than non-foamed microgels (NFMGs), and generated finer pores when jammed. T cell motility is significantly higher in JFMGs than in JNFMGs. Using the JFMG, two compartment structures containing T cells in one compartment and cancer cells in the other compartment are printed. T cells rapidly migrated to the cancer cell compartment and killed the cancer cells. This new bioink enables the ex vivo fabrication of various tissues where immune cell migration is critical.