Armoring a liposome-integrated tissue factor with sacrificial CaCO3 to form potent self-propelled hemostats.

Abstract

The development of hemostatic materials suitable for diverse emergency scenarios is of paramount significance, and there is growing interest in wound-site delivery of hemostasis-enhancing agents that can leverage the body's inherent mechanisms. Herein we report the design and performance of a biomimetic nanoparticle system enclosing tissue factor (TF), the most potent known blood coagulation trigger, which was reconstituted into liposomes and shielded by the liposome-templated CaCO3 mineralization. The mineral coatings, which mainly comprised water-soluble amorphous and vateritic phases, synergized with the lipidated TF to improve blood coagulation in vitro. These coatings served as sacrificial masks capable of releasing Ca2+ coagulation factors or propelling the TF-liposomes via acid-aided generation of CO2 bubbles while endowing them with high thermostability under dry conditions. In comparison to commercially available hemostatic particles, CaCO3 mineralized TF-liposomes yielded significantly shorter hemostasis times and less blood loss in vivo. When mixed with organic acids, the CO2-generating formulation further improved hemostasis by delivering TF-liposomes deep into actively bleeding wounds with good biocompatibility, as observed in a rat hepatic injury model. Therefore, the designed composite mimicry of coagulatory components exhibited strong hemostatic efficacy, which in combination with the propulsion mechanism would serve as a versatile approach to treating a variety of severe hemorrhages.