Versatile Nano-Crosslinker Enhanced Injectable Hydrogel Toward Rapid Hemostasis and Efficient Trauma Repair.

Abstract

Uncontrolled traumatic hemorrhage, often complicated by infection and poor healing, accounts for over 30% of trauma-related deaths worldwide. Injectable hydrogels with robust multi-bond crosslinked networks, integrating fluidity and in situ stability, are promising for efficient hemostasis, but their crosslinkers' relatively single structures limit the multifunctionality required for effective trauma management in resource-scarce environments. Herein, a new class of versatile ε-polylysine grafted manganese dioxide (EPL-g-MnO₂) nano-crosslinkers is synthesized to construct an injectable hydrogel (i.e., OSEG hydrogel). Driven by EPL-g-MnO₂, OSEG hydrogel rapidly achieves stable wet adhesion and efficient hemostasis in critical injuries (e.g., 24.9 s in a rabbit model of cardiac hemorrhage) via imine, hydrogen, and ionic bonds, which form a robust and multifunctional crosslinked network upon full gelation. In the microenvironment of traumatic wounds, OSEG hydrogel undergoes accelerated degradation to further expose EPL-g-MnO₂ and spermidine, thereby providing sufficient antibacterial and pro-healing effects. As a result, OSEG hydrogel achieves a bone volume/total volume 3.3 times that of commercial hemostat SURGIFLO in a rat model of infected cranial defect. This work may inspire the design of advanced injectable hydrogels for synergistic trauma management.