Understanding and Preventing the Spontaneous Gelation of Thiol-Norbornene Hydrogels
Published: 2025
Publication Name: Biomacromolecules
Publication URL: https://doi.org/10.1021/acs.biomac.5c00142
Abstract:
Typically, externally triggered initiators are required for norbornene-modified polysaccharides to undergo thiol−enegelation into a hydrogel. However, anecdotal and reported evidence exists of these prehydrogel solutions undergoing spontaneousthiol−ene gelation without the trigger. Understanding the origin of this spontaneous process would improve the storage ofprehydrogel solutions. We found that polysaccharides with carboxylic acids (e.g., carboxymethyl cellulose) can overcome thebuffering capacity of phosphate-buffered saline (PBS), creating an acidic solution that is required for spontaneous gelation.Investigation using a small molecule model system revealed that acidic pH and trace metal ions increase the reaction rate and theconversion to the thiol−ene product. We concluded that the self-initiated thiol−ene reaction resulted from a Fenton-like reactioncatalyzed by trace metal impurities, such as iron(II), that generate reactive oxygen species (ROS) that initiate the reaction. Using thisknowledge, we developed strategies to inhibit spontaneous gelation and increase the working time of prehydrogel solutions.