Magnetic microwire rheometer reveals differences in hydrogel degradation via disulfide reducing agents

Mucus is composed of a complex network of mucin polymers connected by disulfide bonds. In muco-obstructive diseases, an increase in mucin disulfide crosslinks contributes to pathologic mucus formation, characterized by an increase in mucus viscosity and stiffness. Reducing agents that break down the disulfide bonds between mucins can be used to treat pathologic mucus and restore healthy mucus flow properties. Here, we compare three reducing agents via a rheological assay. A mucus-mimetic disulfide-crosslinked hyaluronic acid hydrogel was treated with thiolated dendritic polyglycerol sulfate (dPGS-SH), N-acetylcysteine (NAC), or dithiothreitol (DTT). A magnetic microwire rheometer was used to track the rheology of the hydrogel over time as the treatment degraded the sample. This nondestructive and minimally invasive technique reveals differences in the degradation mechanism between these reducing agents, with potential implications for drug delivery and the treatment of muco-obstructive diseases.