Cartilage degeneration is a major cause of chronic disability and its treatment usually involves highly invasive procedures. To address this issue, three-dimensional (3D) bioprinting was introduced as a promising tissue engineering approach. However, the structures fabricated with this method are static and lack the dynamic response of native tissues. Moreover, the fabrication of curved or tubular structures remained challenging, especially in the case of soft tissues. Four-dimensional (4D) bioprinting is a newly emerged, next generation biofabrication technology capable of resolving the aforementioned challenges.
In this thesis, an advanced 4D bioprinting method based on multi-material extrusion of two hydrogel-based (bio)inks is reported. This approach allows the fabrication of bilayered scaffolds made from a bottom part of a HA-Tyr precursor and a composite hydrogel top part from alginate and HA-Tyr (Alg/HA-Tyr). The scaffolds demonstrated self-bending upon immersion in aqueous solutions that was driven by the different swelling capacity of the two inks. Compatibility of the inks with extrusion printing was verified by rheological characterization. Control of the obtained curvature was achieved by tuning the infill density, printing angle and layer thickness. Moreover, the effect of crosslinking time as well as the influence of the swelling solvent type in the degree of bending was also investigated. Finally, human mesenchymal stem cells (hMSCs) were mixed with the Alg/HA-Tyr ink and self-bending living scaffolds were bioprinted. The shape-shifted scaffolds were capable of supporting a high cell viability for up to 14 days and remained viable for up to 4 weeks.