Fast-Forming Natural Polysaccharide-Based Hydrogel with Strong Adhesion and Stable Cohesion via Photopolymerization for Rapid Hemorrhage Control

Slow and insufficient sealing is a major problem for natural hydrogels to control incompressible hemorrhage. In this study, a natural macromer with both acrylamido and catechol groups was first designed and synthesized as a hydrogel adhesive precursor, and then the hydrogel was fabricated by photopolymerization. This design with multiple conjugated structures is observed to have the strong electron conjugation effect, i.e., n-π conjugation by UV-induced orbital coupling for electron delocalization and electronic orbital overlap between adjacent chains arising from UV photo-cross-linking as well as between uncosumed acrylamido groups. Owing to this synergistic effect, the natural polysaccharide-based hydrogel demonstrates a rapid gelation within 4.3 s and a significantly enhanced burst pressure with the value of 187.2 ± 21.4 mmHg, as well as strong tissue adhesion, thus providing a fast and stable physical barrier at the bleeding sites. Together with the accelerated clotting <i>in vitro</i> resulting from the promotion of erythrocyte adhesion by the hydrogel, they achieve rapid and efficient hemostasis of rat liver incision and perforation, and femoral artery perforation, which are far superior to the hydrogel with only acrylate groups, commercial gelatin sponge, and gauze. Besides, they are biocompatible and biodegradable via <i>in vitro</i> and <i>in vivo</i> evaluation. Such a molecular design and strategy are suitable for natural polymers with abundant hydroxyl groups, e.g., chitosan and hyaluronic acid, appearing to offer new ideas for the development of hemostatic materials in incompressible hemorrhage control.