A topical platelet-independent multilevel clotting initiator for intraoperative hemostasis

Two processes of erythrocyte aggregation and fibrin forming proceed simultaneously to form a stable blood clot and achieve hemostasis. [Display omitted] •Multilevel initiator-tTFV achieving stable clotting for intraoperative hemostasis.•F127 hydrogel assisting tTFV in depositing onto wound and maximizing hemostasis.•tTFV/F127 mixed hydrogel minimizing the postoperative adhesion. 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.