Activated Platelet-Derived Vesicles for Efficient Hemostatic Activity.

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 alpha IIb beta 3) 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 alpha IIb beta 3 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-1 beta (IL-1 beta) 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.