Activated Platelet-Derived Vesicles for Efficient Hemostatic Activity

Abstract

In this study, activated platelet-derived vesicles (Act-VEs) are developed as a novel hemostatic biomaterial. Spherical Act-VEs (114.40 ± 11.69 nm in size) with surface charges of -24.73 ± 1.32 mV are successfully prepared from thrombin-activated murine platelets with high surface expression of active glycoprotein IIb/IIIa (GP IIb/IIIa, also known as αIIbβ3) and P-selectin. Although nanosized vesicles from resting platelets (VEs) and Act-VEs showed similar sizes and surface charges, Act-VEs formed much larger aggregates in the presence of thrombin and CaCl₂ , compared to VEs. After incubation with fibrinogen, Act-VEs formed much denser fibrin networks compared to platelets or VEs, probably due to active αIIbβ3 on the surfaces of the Act-VEs. After intravenous injection of the Act-VEs, tail bleeding time and the blood loss are greatly reduced by Act-VEs in vivo. In addition, Act-VEs showed approximately sevenfold lower release of pro-inflammatory interleukin-1β (IL-1β) during incubation for 4 days, compared to platelets. Taken together, the formulated Act-VEs can serve as a promising hemostatic biomaterial for the efficient formation of fibrin clots without releasing pro-inflammatory cytokine.

Keywords: activated platelet-derived vesicles; fibrin clot; hemostasis; inflammatory cytokine; platelet activation; platelet-derived vesicles.