Injectable Hydrogels Exhibiting Real-Time In Situ Reinforcement under Dynamic Mechanical Conditions

Biocompatible injectable hydrogels hold significant promise for noninvasive and minimally invasive tissue defects filling and repair applications. However, many tissues are subjected to dynamic mechanical environments. The mechanical properties of hydrogels are significantly affected by long-term dynamic mechanical stimulation after injection. Therefore, when injectable systems are applied to tissue defects for its filling and repair, it is urgent to activate relevant mechanisms that compensate for this strength loss in situ. In this study, we designed and synthesized dibromocyclopropane force-responsive micelles, and combined with our previously proposed “microunit inheritance reformation” strategy, we synthesized injectable hydrogels capable of responding to dynamic force environments to achieve real-time in situ reinforcement for the first time. The system exhibits good injectability and biocompatibility with the reformed hydrogel after injection, effectively inheriting the mechanical properties of the parent hydrogel. The formed network can effectively transmit external dynamic mechanical signals to deform the micelles, which triggers the dibromocyclopropane group to break and open the ring and then cross-links with the hyaluronate preexisting in the hydrogel to strengthen the original network in situ. Taking a physically interacting hydrogel synthesized from NaSS and DMAEA-Q as a model, the strength of the reformed force-responsive hydrogel (as-reformed PA-E) enhanced to 1.7 times that of the original hydrogel after 7 days of prolonged high-frequency biomechanical stimulation at 100 Hz. Meanwhile, by replacing different parent hydrogels and inheriting their initial mechanical properties, the force-responsive injectable system could meet diverse mechanical demands, suggesting the universality of our present strategy. This study provides insights for the synthesis of injectable hydrogels used in noninvasive minimally invasive defect filling applications.