Improved Resolution and Fidelity of Droplet-Based Bioprinting by Upward Ejection

Bioprinting has emerged as a powerful biofabrication technology with widespread applications in biomedical fields because of its superiority in high-throughput, high-precision, 3D structure fabrication. For bioprinting, two of the most important parameters are the printing precision (i.e., droplets resolution) and structural fidelity (i.e., conformity of the printed objects to the design). The major factors that hinder resolution and fidelity are gravity and impact force between printed droplets and substrate. However, existing solutions to these two issues, including decreasing droplet volume and introducing sacrificial materials, cause other problems, such as complexity or poor biocompatibility. Here, we reported a variant 3D bioprinting technique, termed as upward bioprinting, in which the nozzle of bioprinter is overturned and the ejection direction is opposite to gravitational force. Employing this technique, we fabricated discrete droplets, continuous lines, and 3D multilayer constructs using alginate and gelatin methacrylate (GelMA). The characterizations show that the upward bioprinting could improve the resolution and also fidelity as compared with the conventional downward bioprinting. Meanwhile, this method enables cell printing without affecting the viability. In addition, this method can be easily implemented without upgrading any hardware. Such an upward bioprinting technique could be an alternative to scale down microtissues and to fabricate 3D complex bioconstructs. We envision that the upward bioprinting, as a general method, could be extended to other bioprinting processes or applied to 3D bioprinting in outer space.