A Visible Light-Curable Biosynthetic Hybrid Hydrogel for Artificial Mucus Consisting of Mucins and Boronic Acid-Containing Polymers

Animal mucus, serving as a barrier to protect the mucosal surface and as a habitat for symbiotic bacteria, can be regarded as a hydrogel consisting of mucin and proteins linked through reversible bonds. Therefore, biosynthetic integrated hydrogels designed based on a strategy to hybridize mucins with synthetic polymers may mimic the function of mucus. Employing the interaction of mucins and boronic acids, we report a method to form hydrogels consisting of mucin and boronic acid-containing polymers, which are stable under physiological conditions. The hydrogels were prepared by visible light-initiated copolymerization of 3-acrylamidophenylboronic acid and N,N-dimethylacrylamide in the presence of mucins from different animal sources. Rheological measurements revealed that boronate ester bonds served as dynamic cross-links to yield hydrogels. Swelling studies in phosphate-buffered saline demonstrated that the hydrogels exhibited improved stability without dissolution compared to that of the hydrogels formed by mixing mucin with boronic acid-containing polymers. The present method also enabled photopatterning of the hydrogel on a glass substrate, affording hydrogel constructs of predesigned geometries with a printing resolution of ca. 0.2 mm. The printed hydrogels were applied to scaffolds for intestinal bacteria; Lactobacillus rhamnosus GG and Bifidobacterium longum strains exhibited proliferation and distinct dissolution of the gels depending on the bacterial strain and the seeding density. Mechanistic studies suggested that acidic metabolites produced by bacteria interfered with boronic acid–mucin bonds, thereby accelerating dissolution of the gels. These observations allow us to use mucin–boronic acid hydrogels as artificial mucus with tunable viscoelasticity, printability, and compatibility with bacteria.