Digital Assembly of Spherical Viscoelastic Bio-ink Droplets (DASP): a conceptually new bioprinting technology*

Three-dimensional (3D) bioprinting additively assembles bio-inks to manufacture tissue-mimicking biological constructs, but with the typical building blocks limited to one-dimensional filaments. Here, we develop a voxelated bioprinting technique for the digital assembly of spherical particles (DASP), which are effectively zero-dimensional voxels – the basic unit of 3D structures. We show that DASP enables on-demand generation, deposition, and assembly of viscoelastic bio-ink droplets. Using DASP, we create mechanically robust, multiscale porous scaffolds composed of interconnected yet distinguishable hydrogel particles. For instance, we showcase the distinctive capability of voxelated bioprinting by creating highly complex 3D structures such as a hollow sphere. Moreover, we demonstrate the application of the scaffolds in encapsulating human pancreatic islets for 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 transforming basic and applied biomedicine.