Digital Assembly of Spherical Bio-Ink Particles 10 views

Biological tissues are not a random assembly of cells but a hierarchical and tightly controlled three-dimensional (3D) organization of various cell types. Yet most 3D cell culture systems start with clusters or a random assembly of cells by assuming that the originally random cells can self-organize over time—a premise recognized as questionable. Analogues of pixels to two-dimensional (2D) pictures, voxels—in the form of small cubes or spheres—are the basic units of 3D objects. Digital assembly of bio-ink voxels may provide an approach to engineering heterogeneous yet tightly organized 3D tissue mimics. However, this approach requires precisely manipulating highly viscoelastic bio-ink voxels in 3D space, which represents a grand challenge in both soft matter science and biomanufacturing. Here, we develop a voxel-bioprinting technique for the digital assembly of spherical particles (DASP). We show that DASP enables on-demand generation, deposition, and assembly of viscoelastic bio-ink droplets in 3D space. In parallel, we establish the nonlinear fluid mechanics associated with all-aqueous printing of viscoelastic bio-ink droplets in yield-stress fluids, a process critical to DASP printing. By integrating advances in biomaterials, software, and hardware engineering, we create mechanically robust, multiscale porous scaffolds composed of interconnected yet distinguishable hydrogel particles, encapsulating multiple cell types in prescribed spatial arrangements. Moreover, we demonstrate applications of the voxel-printed scaffolds in probing heterotypic cell-cell interactions in 3D angiogenesis and the treatment type 1 diabetes in rodent models. Our results establish voxel bioprinting as a platform for building complex, highly organized tissue mimics for basic and translational biomedicine.

PHD (Doctor of Philosophy)

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2026-06-28