Sprayable, crosslinker-free, and in situ-forming Schiff-based hydrogels based on oxidized sodium alginate and carbohydrazide-modified gelatin for rapid hemostasis.

Natural polymer hydrogels are used for hemostasis in tissue engineering and regenerative medicine because they retain moisture and adhere to tissues. For effective application, they must be easy to handle, provide pressure, and conform to various wound shapes. To address these challenges, we developed a sprayable, self-crosslinking hydrogel composed of oxidized sodium alginate (OSAlg) and carbohydrazide-modified gelatin (Cm-Gel), which rapidly forms via a Schiff-base reaction without external triggers. We introduce an air-assisted spraying (AAS) system to uniformly cover bleeding sites with high-concentration OSAlg/Cm-Gel hydrogel. Chemical characterization confirmed successful synthesis of both components. When 11 wt% OSAlg and 8 wt% Cm-Gel were sprayed at a 0.9:3 ratio using the AAS system, the hydrogel formed a finely dispersed, uniform coating superior to manual syringe mixing. In a liver bleeding model, the sprayed hydrogel demonstrated significantly enhanced hemostasis compared to OSAlg/Cm-Gel hydrogel sponges and commercially available products. These results highlight the novelty of combining high-concentration natural polymers with an easily deployable AAS platform, enabling rapid gelation and superior adaptability to bleeding. Thus, sprayable, self-crosslinkable OSAlg/Cm-Gel hydrogels prepared via an AAS system offer a promising strategy for rapid and effective bleeding control in clinical applications.