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Bleeding complications are associated with substantial tissue morbidities and mortalities. Biomimetic composite materials that possess the ability to sufficiently stimulate and augment different physiological mechanisms of hemostasis are highly desirable to reduce bleeding-related casualties, which, however, are still largely under-explored. This study aims to develop a composite hemostatic system by combining collagen hydrogel with tissue factor (TF)-integrated liposome and silica nanoparticle, which could integrate the platelet plug-promoting capacity of collagen with the abilities of the latter two components to activate the extrinsic and intrinsic pathways of coagulation respectively. Several hydrogel compositions were synthesized and characterized. We show that lipidated TF and silica were evenly distributed in the collagen-based hydrogels, while exhibiting tunable release kinetics in simulated body fluid. Time-to-coagulation test revealed that each component in the TF-liposome/silica/collagen ternary hydrogels was hemostasis-active, and their combination showed enhanced and potent procoagulant performance, without detectable cytotoxicity against NIH/3T3 model cells. These results suggest that collagen hydrogels with embedded TF-liposome and silica nanoparticle may serve as a platform for an effective hemostatic composite that incorporates all the basic known pathways of coagulation.

Incorporation of tissue factor-integrated liposome and silica nanoparticle into collagen hydrogel as a promising hemostatic system