Low Viscous Bioinks for Extrusion-Based 3D Bioprinting

3D bioprinting is an emerging field that can be described as a robotic additive biofabrication technology that has the potential to build tissues or organs. In general, bioprinting uses a computer controlled printing device to accurately deposit cells and biomaterials into precise architectures with the goal of creating on demand organized multicellular tissue structures and eventually intra-organ vascular networks. Progress in bioprinting have been following two interdependent pathways: 1. development of more precise and versatile bioink deposition techniques; 2. development of bioinks that provide a growth and function-supportive medium to the cells and promote their proper organization and function while minimizing the effect of printing on cell viability and without compromising printing fidelity and stability of the construct. Many bioinks have been formulated for various cells types, but those currently used for 3D printing still have challenges and limitations, mainly low cell viability during printing and limited resolution. To overcome these limitations, we developed a new concept of extrusion-based bioprinting technique, which implements a microfluidic control in the dispensation of the bioink. The coupling of microfluidic platforms with the dispensing system is made possible by the use of a coaxial extrusion head that induces the solidification of the bioink in the form of a hydrogel simultaneously to its deposition. In particular, among other components, the bioink contains alginate, whose gelation is induced by exposing it to a crosslinking solution containing calcium ions. The bioink and the crosslinking solution are delivered respectively through the internal and external needles of a coaxial-needles system. At the ending tip of the dispensing head the two solutions meet causing the immediate solidification of the bioink due to the ionic crosslinking of alginate. In this way, it is possible to deposit hydrogel fibers with dimensions ranging between 150 and 300 µm. The printing conditions described above are mild since bioink viscosity is low and crosslinking conditions can be tuned to be harmless toward encapsulated cells.