A novel pullulan oxidation approach to preparing a shape memory sponge with rapid reaction capability for massive hemorrhage

Abstract

Traditional hemostatic materials on the market have considerable limitations for coping with massive bleeding. Herein, we developed an injectable hemostatic sponge via a pullulan oxidation approach. After an oxidation using NaIO4 at room temperature, the resulting oxidized pullulan provides aldehyde groups to cross-link with the residual hydroxyl groups via the acetal reaction, leading to a hydrogel for lyophilization, thereby producing a porous sponge having highly interconnected macro-pores 89.4–195.4 μm in size. Experimental results show that the oxidized pullulan (OP) sponge possesses good biocompatibility and hemocompatibility. The optimized sponge, OP@0.5 (prepared using 0.5:1 mass ratio of NaIO4 and pullulan), exhibited a high fluid absorption ratio, excellent shape memory property, and robust mechanical elasticity. In addition, the OP@0.5 sponge realized a remarkable hemostatic property, which can be reflected by a lower whole blood clotting index and better aggregation capacities of both blood cell and platelet when compared to commercial gelatin sponge and medical gauze. Furthermore, in vivo hemostatic results demonstrate that OP@0.5 sponge can accomplish rapid hemostasis times for a rat femoral artery injury model (mean value of 40 s) and liver volume defect injury model (mean value of 33.8 s). In contrast, the commercial gelatin sponges presented 230 s and 100 s under the same test condition, respectively. Our data also show that the OP@0.5 sponge provides a good antibacterial effect on both Escherichia coli and Staphylococcus aureus. This study demonstrated a great application potential using pullulan-based material for massive hemorrhage cases.