Blue Light-Cured Thiol-Ene Fish Gelatin: A Tunable Hydrogel Platform for Periodontitis Therapy

Abstract Periodontitis (PD) remains a leading cause of tooth loss in humans and horses. In this study, a visible-light crosslinkable, norbornene-functionalized fish gelatin (GelNB) platform is developed for in situ periodontal tissue engineering. We evaluated the effect of thiolated crosslinkers (DTT vs. GelSH) on GelNB hydrogels crosslinked using a dental lamp in the presence of a Ruthenium/SPS photo-initiator system. Dental pulp mesenchymal stromal cells (DP-MSCs) were encapsulated to assess cytocompatibility, proliferation, and osteogenic potential over 21 days. GelNB-GelSH hydrogels exhibited a superior storage modulus (G'), gel fraction (> 85%), and dexamethasone-loading potential compared to GelNB-DTT. When compared to UV-initiated systems (7.8 kPa), Ru/SPS-initiated hydrogels (0.2 mM Ru/4 mM SPS) surpassed the maximum storage modulus (8.7 kPa). This suggests Ru/SPS facilitates efficient thiol-ene polymerization while leveraging endogenous tyrosine for dityrosine bridge formation. Biologically, after a 7-day recovery phase viability remained stable (> 80%) and a 4-fold metabolic increase was observed by day 14. Osteogenic analysis confirmed a transition from ALP activity (day 7) to robust calcium mineralization (day 14). The GelNB-GelSH platform supports DP-MSC progression to mineralized matrix deposition. Utilizing a standard dental light source for rapid hydrogel formation, this system offers a clinically translatable strategy for periodontal implants.