Aspiration-assisted freeform bioprinting of pre-fabricated tissue spheroids in a yield-stress gel

Controlling the positioning of spheroids in 3D during bioprinting is one of the main challenges hindering the scaffold-free fabrication of biologically-relevant tissues and organs. Here, the authors combine cutting edge aspiration-assisted freeform bioprinting of spheroids with self-healing yield-stress gels, obtaining precise positioning and self-assembly into 3D complex configurations. Bioprinting of cellular aggregates, such as tissue spheroids, to form three-dimensional (3D) complex-shaped arrangements, has posed a major challenge due to lack of robust, reproducible and practical bioprinting techniques. Here, we demonstrate 3D aspiration-assisted freeform bioprinting of tissue spheroids by precisely positioning them in self-healing yield-stress gels, enabling the self-assembly of spheroids for fabrication of tissues. The presented approach enables the traverse of spheroids directly from the cell media to the gel and freeform positioning of the spheroids on demand. We study the underlying physical mechanism of the approach to elucidate the interactions between the aspirated spheroids and the gel's yield-stress during the transfer of spheroids from cell media to the gel. We further demonstrate the application of the proposed approach in the realization of various freeform shapes and self-assembly of human mesenchymal stem cell spheroids for the construction of cartilage and bone tissues.