Injectable Self-Expanding/Self-Propelling Hydrogel Adhesive with Procoagulant Activity and Rapid Gelation for Lethal Massive Hemorrhage Management.

ABSTRACT

Developing hydrogels that can quickly reach deep bleeding sites, adhere to wounds, and expand to stop lethal and/or noncompressible bleeding in civil and battlefield environments remains a challenge. Herein, an injectable, antibacterial, self-expanding, and self-propelling hydrogel bioadhesive with procoagulant activity and rapid gelation is reported. This hydrogel combines spontaneous gas foaming and rapid Schiff base crosslinking for lethal massive hemorrhage. Hydrogels have rapid gelation and expansion rate, high self-expanding ratio, excellent antibacterial activity, antioxidant efficiency, and tissue adhesion capacity. In addition, hydrogels have good cytocompatibility, procoagulant ability, and higher blood cell/platelet adhesion activity than commercial combat gauze and gelatin sponge. The optimized hydrogel (OD-C/QGQL-A30) exhibits better hemostatic ability than combat gauze and gelatin sponge in rat liver and femoral artery bleeding models, rabbit volumetric liver loss massive bleeding models with/without anticoagulant, and rabbit liver and kidney incision bleeding models with bleeding site not visible. Especially, OD-C/QGQL-A30 rapidly stops the bleedings from pelvic area of rabbit, and swine subclavian artery vein transection. Furthermore, OD-C/QGQL-A30 has biodegradability and biocompatibility, and accelerates Methicillin-resistant S. aureus (MRSA)-infected skin wound healing. This injectable, antibacterial, self-expanding, and self-propelling hydrogel opens up a new avenue to develop hemostats for lethal massive bleeding, abdominal organ bleeding, and bleeding from coagulation lesions.