Therapeutic‐Gas‐Responsive Hydrogel

Nitric oxide (NO) is a crucial signaling molecule with various functions in physiological systems. Due to its potent biological effect, the preparation of responsive biomaterials upon NO having temporally transient properties is a challenging task. This study represents the first therapeutic-gas (i.e., NO)-responsive hydrogel by incorporating a NO-cleavable crosslinker. The hydrogel is rapidly swollen in response to NO, and not to other gases. Furthermore, the NO-responsive gel is converted to enzyme-responsive gels by cascade reactions from an enzyme to NO production for which the NO precursor is a substrate of the enzyme. The application of the hydrogel as a NO-responsive drug-delivery system is proved here by revealing effective protein drug release by NO infusion, and the hydrogel is also shown to be swollen by the NO secreted from the cultured cells. The NO-responsive hydrogel may prove useful in many applications, for example drug-delivery vehicles, inflammation modulators, and as a tissue scaffold.