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.