A topical platelet-independent multilevel clotting initiator for intraoperative hemostasis

Abstract

Quick and stable clotting is essential in topically controlling intraoperative hemorrhage for patients with chemotherapy-induced thrombocytopenia. Here, we proposed and validated a kind of vesicle originated from gene-engineering cell membrane to manage uncontrolled bleeding with double clotting-triggering strategy. The vesicle constitutively exhibited truncated tissue factor (tTF) protein and phosphatidylserine (PS), thus function as a fibrin growth stimulus and erythrocyte attractant initiator in vitro and in vivo. Erythrocytes assembled in blood clot protected formed fibrin from fibrinolysis while the grown fibrin network enhanced erythrocyte aggregation in situ. Notably, these double clotting-triggering processes worked synergistically to constitute a positive feedback effect to quickly and potently form fibrinolysis-resisted erythrocyte-modified fibrin structures and achieve more stable clotting than the commonly used thrombin and gelatin coagulant. Furthermore, FDA-approved biocompatible Pluronic F127 hydrogel was rationally introduced to assist vesicles depositing onto the wound, thereby maximizing the hemostatic activity and minimizing the postoperative adhesion in a hemorrhage model with cyclophosphamide-induced myelosuppression. This multi-level coagulant method reported here sheds new light on controlling bleeding when patients with myelosuppression undergo surgery.