Mucus-Inspired Self-Healing Hydrogels: A Protective Barrier for Cells Against Viral Infection

Mucus is a dynamic biological hydrogel, composed primarily of the glycoprotein mucin, exhibits unique biophysical properties and forms a barrier protecting cells against a broad spectrum of viruses. Here we developed a polyglycerol sulfate‐based dendronized mucin‐inspired copolymer (MICP‐1) with ∼10% repeating units of activated disulfide as cross‐linking sites. Cryo‐EM analysis of MICP‐1 reveals an elongated single‐chain fiber morphology. MICP‐1 shows potential inhibitory activity against many viruses such as HSV‐1 and SARS‐CoV‐2 (including variants such as Delta and Omicron). MICP‐1 produces hydrogels with viscoelastic properties similar to healthy human sputum and with tuneable microstructures using linear and branched PEG‐thiol as cross‐linkers. Single particle tracking microrheology, EPR and Cryo‐SEM were used to characterize the network structures. The synthesized hydrogels exhibit self‐healing properties, along with viscoelastic properties that are tuneable through reduction. A transwell assay was used to investigate the hydrogel's protective properties against viral infection against HSV‐1. Live‐cell microscopy confirmed that these hydrogels can protect underlying cells from infection by trapping the virus, due to both network morphology and anionic multivalent effects. Overall, our novel mucin‐inspired copolymer generates mucus‐mimetic hydrogels on a multi‐gram scale. These hydrogels can be used as a models for disulfide‐rich airway mucus research, and as biomaterials. This article is protected by copyright. All rights reserved