Magneto-Archimedes based 3D cell economic bioassembly.

Abstract

Constructing three-dimensional (3D) cell assemblies is a critical step in bioengineering, and biomimetic fidelity largely depends on cellular density and spatial distribution. However, directly increasing cell density in bioinks often causes substantial cell loss during bioprinting. Here, we introduce a Magneto-Archimedes effect based 3D cell economic bioassembly strategy (3D MACE) that achieves high cell density (up to 10⁸ cells/mL), low cell loss (<5%), high controllability, and excellent accessibility. Using a vertically aligned pair of magnet arrays with identical polarization direction, a 3D magnetic field pattern was generated in the intervening space, which remotely drive and assemble diamagnetic cells in a paramagnetic culture medium to form 3D configurations according to the magnetic field patterns. This setup is easy to assemble, extends the effective manipulation height, and enables complex 3D architectures beyond spheroid based assemblies. The 3D MACE method allows precise cell manipulation within confined and structurally complex environments (e.g., porous scaffolds and meshes), facilitates the formation of customized patterns such as the Bagua trigram, and automatically separates cells in distributions by mass density. Using this approach, we readily generated 3D cell migration and angiogenesis models in-vitro. This work presents a novel 3D bioassembly strategy that effectively resolves the trade off between achieving high density cell constructs and minimizing cell loss during biofabrication.