Mechanically robust, biocompatible, and durable PHEMA-based hydrogels enabled by the synergic effect of strong intermolecular interaction and suppressed phase separation

Poly(2-hydroxyethyl methacrylate) (PHEMA) hydrogel is highly biocompatible and stable, but its actual application in soft-tissue replacement is limited by its poor mechanical properties. This study develops a facile strategy to construct PHEMA-based hydrogels with the highest strength and toughness ever reported. The strategy relies on introducing robust coordination interactions between the carboxylate groups of copolymerized maleic acid (MA) units and Fe3+ to suppress the phase separation of PHEMA chains from aqueous solution, thereby inducing a homogeneous network. The homogeneous network can avoid stress concentrations, and dynamic coordination crosslinking can effectively dissipate energy and simultaneously maintain network elasticity. The synergistic effects of these two factors impart exceptionally high tensile strength (3.44 MPa), elastic modulus (14.22 MPa), and toughness (4.17 MJ/m3) to the hydrogels, which are 22.7, 43.1, and 24.2 times higher than those of pure PHEMA hydrogels, respectively. Such mechanical properties are comparable to human nasal and auricular cartilage. The hydrogels manifest outstanding self-recovery properties and fatigue resistance, which are essential for long-term and sustainable use. In vitro cell and in vivo animal experiments show that this strategy does not sacrifice the excellent biocompatibility and stability of the PHEMA hydrogels. These PHEMA-based hydrogels, with excellent mechanical properties, fatigue resistance, and biocompatibility, are promising candidates for replacing diseased or damaged nasal and auricular cartilage.