A disulfide-Fe³⁺ crosslinking strategy for tough hydrogel networks with complete photo- and biochemical degradability

Conventional photodegradable hydrogels rely primarily on photocleavable moieties that respond only to light stimuli, often exhibiting weak mechanical strength and limited biodegradability and multifunctionality. In particular, achieving strong mechanical properties in photodegradable hydrogels while simultaneously incorporating additional degradation pathways, such as biodegradability, remains challenging. In this study, we present a disulfide-Fe³⁺ dual-crosslinking strategy that combines high mechanical robustness with complete dual-trigger degradability in double-network hydrogels. As a representative system, we implemented this strategy using a polyacrylamide/alginate double-network hydrogel architecture. This polyacrylamide/alginate/BAC/Fe³⁺ double-network hydrogel is hereafter referred to as the PABF hydrogel. In this system, N,N'-bis(acryloyl)cystamine (BAC) functions as a dynamic disulfide-based covalent crosslinker, while Fe³⁺ ions serve as ionic crosslinkers, forming a synergistic double-network structure in which either UV irradiation or L-cysteine treatment can disrupt both the covalent and ionic networks, thereby enabling complete degradation of a mechanically robust hydrogel. Owing to the reversible nature of the disulfide network, the hydrogel can reform after degradation, allowing light-guided self-adhesion and structural reconfiguration. In vitro cell studies further confirm biocompatibility before and after degradation. More broadly, the combined use of disulfide and Fe³⁺ crosslinking motifs provides a transferable strategy within the double-network framework for constructing mechanically robust yet dual-degradable hydrogel systems capable of incorporating diverse monomer functionalities while maintaining toughness and dual-trigger degradability.