Rapid Biofabrication of Printable Dense Collagen Bioinks of Tunable Properties

Abstract Recent convergence of the 3D printing of tissue‐like bioinks and regenerative medicine offers promise in the high‐throughput engineering of in vitro tissue models and organoids for drug screening and discovery research, and of potentially implantable neo‐tissues with tailored structural, biological, and mechanical properties. However, the current printing approaches are not compatible with collagen, the native scaffolding material. Herein, a unique biofabrication approach that uses automated gel aspiration‐ejection (GAE) is reported to potentially overcome these challenges. Automated‐GAE generates highly defined, aligned, dense collagen gel bioinks of various geometries (i.e., cylindrical, quadrangular, and tubular), dimensions, as well as tunable microstructural and mechanical properties that modulate seeded cellular responses. By densifying initial naturally derived reconstituted collagen hydrogels incorporating cells, automated‐GAE generates mini‐tissue building blocks with tailored protein fibril density and alignment, as well as cell loading, density and orientation according to the intended use. Surprisingly, a simple mathematical relationship defining the bioink compaction factor is found to be highly effective in predicting the initial and temporal properties of the bioinks in culture. Therefore, automated‐GAE will potentially also enable a fourth dimension to biofabrication, where cell–cell communications and cell‐extracellular matrix interactions as a function of time in culture can be predicted and modeled.