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Mucus is a self‐healing gel that lubricates the moist epithelium and provides protection against viruses by binding to viruses smaller than the gel's mesh size and removing them from the mucosal surface by active mucus turnover. As the primary nonaqueous components of mucus (≈0.2%–5%, wt/v), mucins are critical to this function because the dense arrangement of mucin glycans allows multivalence of binding. Following nature's example, bovine submaxillary mucins (BSMs) are assembled into "mucus‐like" gels (5%, wt/v) by dynamic covalent crosslinking reactions. The gels exhibit transient liquefaction under high shear strain and immediate self‐healing behavior. This study shows that these material properties are essential to provide lubricity. The gels efficiently reduce human immunodeficiency virus type 1 (HIV‐1) and genital herpes virus type 2 (HSV‐2) infectivity for various types of cells. In contrast, simple mucin solutions, which lack the structural makeup, inhibit HIV‐1 significantly less and do not inhibit HSV‐2. Mechanistically, the prophylaxis of HIV‐1 infection by BSM gels is found to be that the gels trap HIV‐1 by binding to the envelope glycoprotein gp120 and suppress cytokine production during viral exposure. Therefore, the authors believe the gels are promising for further development as personal lubricants that can limit viral transmission. [ABSTRACT FROM AUTHOR]

Hydrogels made of crosslinked macromolecules used in regenerative medicine technologies can be designed to affect the fate of surrounding cells and tissues in defined ways. Their function typically depends on the type and number of bioactive moieties such as receptor ligands present in the hydrogel. However, the detail in how such moieties are presented to cells can also be instrumental. In this work, how the crosslinking architecture of a hydrogel can affect its bioactivity is explored. It is shown that bovine submaxillary mucins, a highly glycosylated and immune‐modulating protein, exhibit strikingly different bioactivities whether they are crosslinked through their glycans or their protein domains. Both the susceptibility to enzymatic degradation and macrophage response are affected, while rheological properties and barrier to diffusion are mostly unaffected. The results suggest that crosslinking architecture affects the accessibility of the substrate to proteases and the pattern of sialic acid residues exposed to the macrophages. Thus, modulating the accessibility of binding sites through the choice of the crosslinking strategy appears as a useful parameter to tune the bioactivity of hydrogel‐based systems. [ABSTRACT FROM AUTHOR]