Swift Covalent Gelation Coupled with Robust Wet Adhesive Powder: A Novel Approach for Acute Massive Hemorrhage Control in Dynamic and High-Pressure Wound Environments

The quest for efficient hemostatic agents in emergency medicine is critical, particularly for managing massive hemorrhages in dynamic and high-pressure wound environments. Traditional self-gelling powders, while beneficial due to their ease of application and rapid action, fall short in such challenging conditions. To bridge this gap, the research introduces a novel self-gelling powder that combines ultrafast covalent gelation and robust wet adhesion, presenting a significant advancement in acute hemorrhage control. This ternary system comprises epsilon-polylysine (epsilon-PLL) and 4-arm polyethylene glycol succinyl succinate (4-arm-PEG-NHS) forming the hydrogel framework. Na2HPO4 functions as the "H+ sucker" to expedite the amidation reaction, slashing gelation time to under 10 s, crucial for immediate blood loss restriction. Moreover, PEG chains' hydrophilicity facilitates efficient absorption of interfacial blood, increasing the generated hydrogel's cross-linking density and strengthens its tissue bonding, thereby resulting in excellent mechanical and wet adhesion properties. In vitro experiments reveal the optimized formulation's exceptional tissue compliance, procoagulant activity, biocompatibility and antibacterial efficacy. In porcine models of heart injuries and arterial punctures, it outperforms commercial hemostatic agent Celox, confirming its rapid and effective hemostasis. Conclusively, this study presents a transformative approach to hemostasis, offering a reliable and potent solution for the emergency management of massive hemorrhage. This study presents a self-gelling powder comprising Na2HPO4 as the "H+ sucker" with epsilon-PLL and 4-arm-PEG-NHS as the hydrogel skeleton. Na2HPO4/epsilon-PLL/PEG demonstrates ultrafast self-gelation and robust wet adhesion. Applied to the dynamic and high-pressure wounds, the powder rapidly absorbs interfacial blood and undergoes an ultrafast powder-hydrogel transition that creates robust physical sealing while aggregating blood cells to accelerate coagulation. image