Dual-Crosslinkable Gallol Bioinks via pH-Controlled Oxidation and Photocrosslinking with Enhanced Shear Thinning and Viscoelastic Behavior

Abstract

Our research work proposes a dual crosslinking approach to address the limitations of the gallol-mediated auto-oxidation approach in bioprinting, where rapid oxidative crosslinking can cause premature gelation, leading to clogging or printing failure. We enabled a gallol hydrogel ink to be printable via extrusion-based 3D bioprinting by utilizing its temporal shear-thinning properties. By raising the pH level, interactions between gallol-modified hyaluronic acid methacrylate (HAMA-GA) can be triggered to form a weak hydrogel. This feature provides injectability and extrudability for the hydrogels. Subsequent photocrosslinking results in indefinite oxidative crosslinking. The oxidative coupling in HAMA-GA was partially inhibited by UV light during the photocrosslinking step. As a result, the printed hydrogel formed a dual-crosslinked network containing both oxidative and photo-induced bonds, which contributed to enhanced structural stability over time. Our proposed approach addresses the challenges of gallol-mediated oxidation, including overgelation that hinders extrusion in 3D bioprinting, offering a promising solution for improved printability and shape fidelity. HAMA-GA ink was bioprintable at pH 5.5 using an extrusion-based 3D printer, showing cytocompatibility (∼95 % viability). This strategy is valuable for designing hydrogel inks with tunable properties for 3D bioprinting while maintaining tissue adhesive properties of gallol moieties.