The remarkable defensive ability of native mucus against pathogens has encouraged scientists to map its structure–-property correlation and its influence on immune defense mechanisms. However, its poorly defined structure, source-dependent composition, and low availability limit the usefulness of native mucus in the laboratory. This gap creates a strong demand for the development of synthetic mucus-mimetic materials. Here, we report a straightforward strategy for constructing mucus-mimetic hydrogels through photo-regulated disulfide crosslinking. Light-responsive 1,2-dithiolane attached to a linear polyglycerol sulfate (lPGS) backbone allows the macromolecular building blocks to crosslink and form the hydrogel, which mirrors the chemistry of native mucus hydrogel formation with its disulfide-linked mucin chains. The viscoelastic properties of the hydrogel can be easily tuned by controlling both the light exposure time and the number of 1,2-dithiolane units within the polymer backbone. Furthermore, localized UV irradiation allows for spatially resolved hydrogel formation. Importantly, this synthetic polymer can directly crosslink with native mucin, bovine submaxillary mucin (BSM), to convert it into a hydrogel at physiological pH. The versatility of this approach – hydrogel formation via photo-regulated disulfide crosslinking – can be used to develop a synthetic mucus model.
