Injectable, in-situ forming, tunable, biocompatible gelatin hydrogels for biomedical applications

Gelatin hydrogels have drawn attention for their diverse biomedical applications due to their flexible physiochemical properties. However, such gelatin hydrogels are made of toxic crosslinkers and photoinitiators, restricting their non-invasive deep tissue application. The in-situ forming chemical crosslinked without such toxic crosslinker and UV light has not been explored under physiological conditions. This study establishes a simple method to fabricate an injectable click-chemistry-based in-situ forming gelatin hydrogel in a physiological environment (without toxic UV or photoinitiator) with tunable physiochemical properties to modulate cellular response. Using Divinyl Sulfone (DVS) modification, gelatin hydrogel (GelVS) is optimized with tunable degradation properties, moduli (100 Pa -1000 Pa), gelation time, swelling, degradation, and viscoelastic behaviour. The in-vitro results using fibroblast and stem cells show that the hydrogel and its precursors were cytocompatible with diverging feedback of cells as the modulus varies. The in-vivo analysis for injectability, degradation, and biocompatibility of the GelVS hydrogel displays their biocompatible nature and lasts up to 30 days at the injecting site. Overall results indicate that DVS-modified GelVS hydrogel will be a great system with tunable physicochemical properties to modulate favorable cellular response for tissue regeneration and non-invasive deep tissue application.