Digital Assembly of Spherical Viscoelastic Bio-Ink Particles

3D bioprinting additively assembles bio-inks to manufacture tissue-mimicking biological constructs, but with the typical building blocks limited to 1D filaments. Here, it is developed a voxelated bioprinting technique for the digital assembly of spherical particles (DASP), which are effectively 0D voxels-the basic unit of 3D structures. It is shown that DASP enables on-demand generation, deposition, and assembly of viscoelastic bio-ink droplets. A two-parameter diagram is developed to outline the viscoelasticity of bio-inks required for printing spherical particles of good fidelity. Moreover, a strategy is developed for engineering bio-inks with independently controllable viscoelasticity and mesh size, two of the most important yet intrinsically coupled physical properties of biomaterials. Using DASP, mechanically robust, multiscale porous scaffolds composed of interconnected yet distinguishable hydrogel particles are created. Finally, it is demonstrated the application of the scaffolds in encapsulating human pancreatic islets for sustained responsive insulin release. Together with the knowledge of bio-ink design, DASP might be used to engineer highly heterogeneous, yet tightly organized tissue constructs for therapeutic applications.