Fabrication of Multiple-Layered Hydrogel Scaffolds with Elaborate Structure and Good Mechanical Properties via 3D Printing and Ionic Reinforcement

A major challenge in three-dimensional (3D) printing of hydrogels is the fabrication of stable constructs with high precision and good mechanical properties and biocompatibility. Existing methods typically feature complicated reinforcement steps or use potentially toxic components, such as photocuring polymers and crosslinking reagents. In this study, we used a thermally sensitive hydrogel, hydroxybutyl chitosan (HBC), for 3D-printing applications. For the first time, we demonstrated that this modified polysaccharide is affected by the specific ion effect. As the salt concentration was increased and stronger kosmotropic anions were used, the lower critical solution temperature of the HBC decreased and the storage modulus was improved, indicating a more hydrophobic structure and stronger molecular chain interactions. On the basis of the thermosensitivity and the ion effects of HBC, a 25-layered hydrogel scaffold with strong mechanical properties and an elaborate structure was prepared via a 3D-printing method and one-step ionic post-treatment. In particular, the scaffold treated with 10% NaCl solution exhibited a tunable elastic modulus of 73.2 kPa to 40 MPa and excellent elastic recovery, as well as biodegradability and cytocompatibility, suggesting the potential for its applications to cartilage tissue repair. By simply controlling the temperature and salt concentrations, this novel approach provides a convenient and green route to improving the structural accuracy and regulating the properties of 3D-printed hydrogel constructs.