Gallol-derived ECM-mimetic adhesive bioinks exhibiting temporal shear-thinning and stabilization behavior.

3D bioprinting is an attractive technique to fabricate well-organized, cell-laden constructs for tissue repair and disease modeling. Although numerous hydrogel bioinks have been developed, materials are still needed that mimic the cellular microenvironment, have the appropriate viscosity and stabilization for printing, and are cytocompatible. Here, we present a unique gallol-modified extracellular matrix (ECM) hydrogel ink that is inspired by rapid fruit browning phenomena. The gallol-modification of ECM components (e.g., hyaluronic acid, gelatin) allowed (i) immediate gelation and shear-thinning properties by dynamic hydrogen bonds on short time-scales and (ii) further auto-oxidation and covalent crosslinking for stabilization on longer time-scales. The gallol ECM hydrogel ink was printable using an extrusion-based 3D printer by exploiting temporal shear-thinning properties, and further showed cytocompatibility (∼95% viability) and on-tissue printability due to adhesiveness of gallol moieties. Printed cell-laden filaments degraded and swelled with culture over 6 days, corresponding to increases in cell density and spreading. Ultimately, this strategy is useful for designing hydrogel inks with tunable properties for 3D bioprinting. STATEMENT OF SIGNIFICANCE: 3D bioprinting is a promising technique for the fabrication of cell-laden constructs for applications as in vitro models or for therapeutic applications. Despite the previous development of numerous hydrogel bioinks, there still remain challenging considerations in the design of bioinks. In this study, we present a unique cytocompatible hydrogel ink with gallol modification that is inspired by rapid fruit browning phenomena. The gallol hydrogel ink has three important properties: i) it shows immediate gelation by dynamic, reversible bonds for shear-thinning extrusion, ii) it allows spontaneous stabilization by subsequent covalent crosslinking after printing, and iii) it is printable on tissues by adhesive properties of gallol moieties. As such, this work presents a new approach in the design of hydrogel inks.