Injectable hydrogels based on mussel-inspired nanocomposite microspheres for non-compressible intra-abdominal hemorrhage control.

Abstract

Background: The development of hemostatic materials for non-compressible intra-abdominal hemorrhage in complex pre-hospital emergency settings remains a formidable challenge. Methods: A novel injectable hydrogel based on mussel-inspired nanocomposite microspheres was designed. The biocompatible hydrogel was formed by hydrating gelatin methacryloyl (GelMA) cryogel microspheres-reinforced with polydopamine (PDA)-intercalated nanoclay-with sterile saline, offering the dual benefits of convenient storage of microspheres and precise delivery to deep bleeding points via injection. Results: The cryogel microspheres, featuring rapid water and blood absorption within 1 second, exhibited outstanding procoagulant capabilities in both in vitro and in vivo experiments, showing potential as hemostatic agents for open wounds. Notably, the on-demand formulated hydrogel effectively controlled severe bleeding within 2 minutes post-injection in rat liver volumetric defect and partial resection models, demonstrating ​significantly enhanced applicability compared to ​bulk hemostatic agents for irregular wounds. Additionally, ultrasound-guided application in a porcine liver ​rupture model confirmed that the hydrogel rapidly filled and sealed deep wounds, interacted with blood components to form stable, large clots adhering to the wound surface, and thus established durable hemostasis. Conclusion: This study presents a promising injectable hemostatic material for pre-hospital emergency hemorrhage control.