Three-dimensional printing of hyaluronate-based self-healing ferrogel with enhanced stretchability

Hydrogels have been frequently employed for three-dimensional (3D) printing, which is a promising tool for fabricating sophisticated structures useful in many biomedical applications. Ferrogels prepared by combining magnetic nanoparticles with hydrogels also have potential in biomedical engineering because of the responsiveness to a magnetic field and remotely controllable properties. However, typical ferrogels, especially those prepared from natural polysaccharides, have limitations concerning their mechanical properties and the fabrication method of complex structures owing to their rigid and brittle properties. In this study, 3D printable and stretchable ferrogel was designed and prepared to overcome these limitations. Hyaluronic acid (HA) derivatives such as hydrazide-modified HA (hHA) and oxidized HA (oHA) were used as the base materials for gel preparation. Self-healing oHA/hHA hydrogels were prepared by the addition of adipic acid dihydrazide (ADH). Self-healing ferrogels with 3D printability were prepared by adding superparamagnetic iron oxide nanoparticles (SPIONs) to oHA/hHA/ADH hydrogels, which improved the stretchability owing to the double network formation (2.1 times its original length). Various 3D constructs were fabricated by an extrusion-based printing method using ferrogel (structural integrity = 94.3 ± 1.5%). The potential to fabricate hydrogel/ferrogel hybrid constructs for tissue engineering was also investigated. This approach for developing customized 3D constructs using magnetic field-responsive and 3D printable hydrogel systems may find useful applications in tissue engineering approaches.