Cooperative Poly(ethylene glycol) Dehydration and Ion-Dependent Electrostatic Interactions Drive Thermally...

Thermoresponsive hydrogels based on flower-micelle assemblies that undergo gelation upon heating are attractive as injectable soft materials. We previously reported that Redox Injectable Gels (RIGs), formed from polyion complex (PIC) flower micelles, exhibit unusually high stiffness together with thermally irreversible gelation. Here, we investigate the physicochemical basis of this distinctive behavior by systematically examining the effects of phosphate buffer concentration and salt species on gelation dynamics, micellar structure, and segmental mobility. Rheological analyses showed that gelation accelerated with increasing buffer concentration, whereas the maximum storage modulus exhibited a nonmonotonic dependence, reaching a minimum at intermediate ionic conditions. Salt addition further modulated gel stiffness in an ion- and concentration-dependent manner, consistent with an ionic window in which moderate electrostatic screening alters electrostatic complexation within PIC cores and may facilitate micellar reorganization, whereas excessive screening at higher ionic strengths suppresses network reinforcement. Complementary dynamic light scattering (DLS), proton nuclear magnetic resonance (¹H NMR), fluorescence quenching, and pyrene solvatochromism collectively indicate that poly(ethylene glycol) (PEG) dehydration-consistent with cloud-point depression under high ionic strength-together with ion-dependent modulation of electrostatic interactions contributes to micelle reorganization and network formation. Collectively, these findings support a cooperative mechanistic framework in which PEG dehydration and ion-dependent modulation of electrostatic interactions jointly contribute to the robust and thermally irreversible gelation of RIGs. This framework provides design principles for tuning ionic environments to engineer mechanically robust thermoresponsive injectable hydrogels for biomedical applications under physiologically relevant ionic conditions. STATEMENT OF SIGNIFICANCE: Thermoresponsive injectable hydrogels are attractive biomaterials, but conventional flower-micelle systems typically exhibit weak mechanical properties and thermoreversible gelation. This study clarifies why redox injectable gels (RIGs), formed from polyion complex flower micelles, exhibit unusually high stiffness together with thermally irreversible gelation. By systematically varying buffer concentration and salt species, we show that gelation is strongly influenced by poly(ethylene glycol) (PEG) dehydration and ion-dependent modulation of electrostatic interactions within PIC micelles. These findings support a cooperative mechanistic framework for understanding salt- and buffer-dependent gelation and provide design principles for developing mechanically robust injectable biomaterials under physiologically relevant ionic environments.