Hydrogels, consisting of hydrophilic three-dimensional (3D) cross-linked networks, have been widely used as a promising scaffold in biomaterial fields owing to their biocompatibility, multi-tunable properties as well as and structural similarity to native tissues. Generally, the mechanical properties of conventional hydrogels originated from the intrinsic rigidity of the polymer chains and the cross-linking density. This inherent poor mechanical behavior resulted from a lack of energy-dissipation mechanisms to prevent the crack propagation. Therefore, their low fracture toughness and brittleness often limit the scope of hydrogel applications.
Double network (DN) hydrogel composed of independently cross-linked rigid and ductile polymer networks, have been proposed as an alternative to compensate for weak mechanical properties of hydrogels. In contrast to interpenetrating networks (IPNs), also a combination of two network structures, the mechanical properties of the combined components are much higher. The DN hydrogels show synergistic effect when comparing with the two independent structures. Therefore, tremendous researches have been conducted since the advent of DN hydrogel. However, there are still some limitations, such as the complicate and time-consumption process for double network formation and the difficulty in controlling gelation properties of DN hydrogels.
To address these issues, we present here a facile method to fabricate injectable DN hydrogels. In this study, in situ cross-linkable DN hydrogels composed of acrylamide (AAm) and 4-arm-PPO-PEO-tyramine (TTA) were prepared via dual Fenton- and enzyme-mediated reactions. By varying the concentration of Fenton’s reagent, the DN hydrogels was rapidly formed and the gelation rate could be easily controlled (5–60 sec). Importantly, in situ cross-linked DN hydrogels showed a 13-fold increase in compressive strength (over 3 MPa) and a 14-fold increase in tensile strength (0.27 MPa) compared to the single network hydrogels. The mechanical properties, elasticity and plasticity of DN hydrogels could be also modulated by simply varying the preparation condition, including cross-linking density and reagents concentrations. At the low cross-linker concentration (< 0.1 wt%), the DN hydrogel stretched up to over 6500% with necking phenomena whereas high cross-linker concentration (> 0.1 wt%) induced fully elastic hydrogels without hysteresis. Human dermal fibroblasts treated with DN hydrogels remained viable, confirming the biocompatibility of the cross-linking system. In conclusion, we have developed a simple, rapid and tunable process to prepare injectable DN hydrogels via Fenton/enzyme reactions, which can be applicable for hard tissue regeneration and replacement, including teeth, bone and cartilage regeneration.