Poor Solvent Solubilization Enables Simultaneous Enhancement of Injectability and Strength in Bone Repair Gels

Injectable gels exhibit advantages in bone repair due to their minimally invasive nature, adaptability to irregular defects, and in situ formation capability. However, their mechanical strength is frequently insufficient. Strategies such as introducing chemical crosslinking, incorporating nanofillers, or inducing phase separation via poor solvents have been employed to enhance gel strength. Nevertheless, these approaches often suffer from drawbacks such as the use of toxic small-molecule crosslinkers, reaction heat, or compromised injectability due to excessive rigidity. In this study, a physically crosslinked gel based on multiple hydrogen bonds was constructed using a polyhydroxy system—poly(hydroxyethyl acrylate/methyl acrylate) and bioactive glass. The compressive modulus of the gel reached 649 kPa, surpassing the typical limit of 420 kPa for purely physically crosslinked injectable hydrogels in bone repair. To ensure injectability, the unique cosolvent effect and lower critical solution temperature (LCST) transition of this copolymer system were leveraged, enabling simultaneous improvement in both injectability and mechanical strength through synergistic effects. Moreover, the hydrogel also exhibited electrical conductivity, a property that plays a crucial role in enhancing bone repair. Finally, experimental validation in a rat calvarial defect model demonstrated the great potential of this hydrogel for bone regeneration applications.