In situ-forming hyaluronic acid hydrogel through visible light-induced thiol-ene reaction

Here we present hyaluronic acid (HA) hydrogels crosslinked via thiol-ene reaction initiated by visible blue light exposure in the presence of riboflavin phosphate (RFP). The gelation procedure is rapid and proceeds as effectively with exposure to blue light as it does with UV light. We successfully initiated the thiol-ene reaction by RFP with blue light, which triggered gelation that proceeds over about 5 min at 36 °C after an initial small change in modulus upon light exposure. Gel transparency was also evaluated, and the HA gel exhibited over 80% transmittance in the visible spectrum. The degradation and protein release kinetics of the photo-crosslinked HA hydrogel are also presented. The capacity of blue light to initiate thiol-ene reaction was equal to or more effective than UV light of the same energy. The cytocompatibility of hydrogels was evaluated using corneal fibroblasts, and the light-induced fabrication procedure and resultant gel materials did not affect cell viability. The results indicate that an RFP-based, BL-initiated photo-reaction to gelate HA may be an effective and promising modality for applications where in situ gelation is desired.