3D-bioprinting of self-healing hydrogels

Self-healing hydrogels are the most promising hydrogel-ink materials, especially for extrusion-based 3D-bioprinting, because, unlike traditional hydrogels, the bonds as well as their initial structure, properties and functionality can be recovered after extrusion, which together with shear-thinning property enables safe printing for cells, but also shape stability of the construct after printing. In addition to tunable viscoelastic properties given by these inks, they can also respond to cell forces by rearranging the network, while maintaining bulk physiological properties. Currently, mainly extrusion-based bioprinting has been used for these types of dynamic inks. Some basic 3D structures, such as letters, grids and patterns, have been printed with high shape fidelity and high cell viability using traditional 3D-bioprinting. More complex spiral, pyramidal, or vascular tree structures have also been printed using so-called gel-in-gel printing technique, and even some overhang geometries without the need for additional support bath. The current limitation of self-healing hydrogel inks has been their poor mechanical stability, which has been improved, for example, using additional crosslinking. However, the opposing characteristics of self-healing hydrogels, like toughness and fast self-healability, remain a challenge. Therefore, more studies are needed in the future to improve the self-healing hydrogel inks. This review collects some of the most relevant studies related to self-healing 3D-bioprintable hydrogels. It also discusses the importance of self-healing and shear-thinning properties for bioinks and bioprinted constructs, the effects of self-healing hydrogel bioinks and bioprinting on cells (and vice versa), as well as the current status and future prospects of self-healing hydrogel bioinks.