A comparative Study between Thiol-ene and Acrylate Photocrosslinkable Hyaluronic Acid Hydrogel inks for Digital Light Processing

Photopolymerizable formulations based on the thiol-ene crosslinking are considered better alternatives than methacrylated counterparts for light-based fabrication processes. The thiol-ene photoreaction requires lower light doses for polymerization and leads to networks with lower molecular heterogeneity. For hydrogels at low polymer concentrations as used in bioinks (<8 wt%), faster polymerization rates and higher conversion of the crosslinking reaction have been reported in thiol-ene systems. Here we quantify further differences between thiol-ene and methacrylated crosslinked hydrogels for HA functionalized with norbornene, allyl ether or methacrylate groups. We show storage stability of the thiol-ene hydrogel precursors over 15 months, 3.8 times higher than the methacrylated derivative. Photorheology experiments demonstrated up to 4.7-times faster photocrosslinking. Network formation in photoinitiated thiol-ene HA crosslinking allows higher temporal control than in methacrylated HA, which shows long post-illumination hardening. Using digital light processing, 4% w/v HA hydrogels polymerized with a dithiol crosslinker allowed printing of 13.5x4x1 mm3 layers with holes of 100 µm resolution within 2 s. Considering that ene-derivatized hydrogel precursors are less commercially available than methacrylated counterparts, our results are important to estimate the extent to which the synthetic effort of introducing –ene functions can pay off in the printing step.