Mussel-Inspired Naturally Derived Double-Network Hydrogels and Their Application in 3D Printing: From Soft, Injectable Bioadhesives to Mechanically Strong Hydrogels

As promising candidates for tissue engineering, hydrogels possess great potential, especially in bioadhesives and load-bearing tissue scaffolds. However, a strategy for synthesizing hydrogels that could achieve the above requirements remains a challenge. Here, a mussel-inspired naturally derived double-network (DN) hydrogel composed of a special combination of two well-characterized natural polymers, hyaluronic acid and alginate, is presented. The key features are its two-step synthesis strategy, which generates injectable and adhesive properties in the first step and then transforms into a DN hydrogel with high mechanical strength and good resilient properties. Based on this strategy, the DN hydrogel could be tamed into a self-supporting three-dimensional (3D) printable bioink. As a rheological modifier, alginate was used to lubricate the covalent cross-linking hydrogels for better extrusion performance. The incorporation of alginate also enhanced the mechanical performance of the soft covalent network by forming reversible alginate–Ca2+ ionic cross-links, which interpenetrate through the outer water-retention scaffold with delicate weblike structures. In vitro cell culture data indicated that our bioink formulation and printing strategy are compatible with human umbilical vein endothelial cells (HUVECs).