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

Abstract

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).

3D Printing Unique Nanoclay‐Incorporated Double‐Network Hydrogels for Construction of Complex Tissue Engineering Scaffolds

“…The rheological properties of hydrogel precursors play a crucial role in their application as injectable bioinks in 3D printing. [31,44] As shown in Figure 6b, the viscosity of HAMA and Alg was lower than that of nanoclay at a low shear rate. However, the viscosity of the nanoclay and its mixture with HAMA and Alg decreased significantly with increasing shear rate, thus demonstrating typical shear-thinning properties.…”

“…This phenomenon has been commonly observed in hydrogels based on ionic crosslinking networks. [31] Besides, the addition of hyaluronidase could degrade the backbone of HAMA, which leads to the disintegration of covalent HAMA crosslinking networks. [55] Furthermore, Van Gieson's staining of calvarial undecalcified sections was performed to determine the degradation of NIDN hydrogels in vivo and tissue regeneration induced by this process (Figure S16, Supporting Information).…”

“…Characterization of the Hydrogels: The physical and mechanical properties of the hydrogels were characterized according to the previous report. [31] Three replicates were used for each hydrogel composition. Rheological measurements were performed at 25°C on a rheometer (MCR302, Anton Paar, Austria) using a plate-plate geometry (25 mm diameter).…”

“…Our previous work presented a mussel-inspired DN hydrogel composed of HA and Alg, which exhibited good mechanical strength. [31] Benefitting from its two-step synthesis strategy, these HA/Alg hydrogels could be tamed into printable biomaterials. However, the hydrogels are partially covalently crosslinked before printing, which leads to potential instability and discontinuity throughout the printing process.…”

Tuning Surface Morphology of Fluorescent Hydrogels Using a Vortex Fluidic Device

“…Of particular interest, smart hydrogels have been extensively utilized for the sustained release of pharmaceutics with controlled pH [7][8][9], electric fields [10], osmosis [11], molecular structure [12,13], and temperature [14][15][16][17], regulating their swelling properties. In the meantime, numerous studies have been performed to improve the physical, mechanical, and biomedical properties of hydrogels, making them attractive for a wide range of applications [18,19].…”