Graphene oxide reinforced hemostasis of gelatin sponge in noncompressible hemorrhage via synergistic effects

Abstract

Effective hemostasis for noncompressible bleeding has been a key challenge because of the deep, narrow, and irregular wounds. Swellable gelatin is an available hemostatic material but is limited by weak mechanical strength and slow liquid absorption. Herein, the design of a gelatin and graphene oxide (GO) composite sponge (GP-GO) that possesses stable cross-linked networks and excellent absorbability, is reported. The GP-GOs are constructed via the thermal radical polymerization technique, using methacrylate gelatin (Gel-MA) and poly(ethylene glycol) diacrylate (PEGDA) as the crosslinker, while GO is uniformly fixed in the network via the curing reaction to further strengthen the stability. The optimized GP-GO₅ with GO addition (5 wt%) exhibits high porosity (> 90%), distinguished liquid absorption rate (106 ms), rapidly responsive swelling (422% expansion within 10 s), and stable mechanical properties. The addition of GO effectively reinforces coagulation stimulation of GP-GOs though the stimulation of platelets and the enrichment effect at the interface, significantly reducing the blood coagulation index (BCI) (< 17.5%). Hemostatic mechanism study indicated the liquid absorbability of GP-GOs is the critical foundation to trigger the subsequent physical expansion, blood cells enrichment, and coagulation stimulations. Besides, GP-GO₅ exhibits excellent biosafety assessed by hemolysis and cytotoxicity. Under the synergistic effects, the biocompatible GP-GO₅ showed excellent hemostatic properties in the hemostasis of severe bleeding and noncompressible wounds compared with a pure gelatin sponge (GP) and the commercial hemostatic agent Celox™. This study demonstrated a promising candidate for practical application of noncompressible wound hemostasis.

Keywords: Coagulation mechanism; Gelatin; Graphene oxide; Hemostasis sponge; Noncompressible wound.