Architectural Tuning of Redox-Responsive Copolymer Hydrogels: Fast Gelation, Self-Healing, and Superior Mechanics via Block vs Random Networks

Stimulus-responsive hydrogels have emerged as promising candidates for next-generation biomedical materials, yet the direct influence of copolymer architecture on their gelation kinetics, mechanical performance, and adaptive properties remains underexplored. Here, we systematically compare random (poly­(HEMA-co-NIPAM)) and block (poly­(HEMA-b-NIPAM)) copolymer architectures, synthesized via RAFT polymerization and cross-linked with disulfide-containing DTPA, to engineer redox-responsive hydrogels. Notably, random copolymer hydrogels achieve ultrafast gelation within 30 s and display superior elasticity, with a fracture strain of 295.9% at 40 wt % solid content-substantially higher than the 99.0% observed in block copolymer hydrogels. Thermal analysis reveals that random copolymer hydrogels exhibit a maximum degradation temperature of 380 °C, surpassing the 340 °C of block counterparts, while DSC shows a higher glass transition temperature (135 °C vs 125 °C). SEM imaging further demonstrates that random hydrogels possess uniform, interconnected pores (∼20–25 μm), whereas block architectures yield irregular and larger pores (∼35–40 μm). All hydrogels display robust self-healing and reversible gel–sol–gel transitions upon redox cycling, attributable to dynamic disulfide linkages. These results underscore the pivotal role of macromolecular architecture in tuning hydrogel performance, and establish random copolymer networks as promising platforms for smart wound dressings and responsive drug delivery.