Trace-stimuli-triggered controlled degradation for hydrogel adhesives

Abstract Biodegradable hydrogels are promising for tissue adhesives and implantable coatings, but are often limited by harsh degradation triggers and uncontrolled breakdown. Here, we present a biodegradable hydrogel design strategy that leverages a redox-responsive crosslinker with a low activation threshold, enabling spatiotemporally controlled degradation in response to trace levels of reactive oxygen species (ROS). The hydrogel undergoes rapid and complete degradation even under low redox stress, disassembling entirely within 2 hours under 0.1% (w/w) ROS and 24 hours at concentrations as low as 0.0001% (w/w) (37°C). Functioning as a tissue adhesive, the hydrogel forms bonds within 5 seconds, maintains strong wet adhesion (200 J·m⁻²), and exhibits excellent sealing performance in both in vitro and in vivo models, with complete degradation under physiological ROS concentrations (∼0.0000001% (w/w)) occurring over 3 weeks—well aligned with the natural wound healing process. Notably, initial mild degradation triggers chain growth, which reinforces wet adhesion by actively compensating for swelling-induced interfacial weakening. The strategy demonstrates remarkable generality and biocompatibility, facilitating the clinical application of biodegradable materials and minimizing the risk of synthetic residue and contamination.