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.

Platelet-Derived Extracellular Vesicles for Regenerative Medicine

“…Even more, pEVs have an effect on endothelial permeability, which mitigates blood loss too [34]. Further studies report that aggregates of thrombin activated pEVs decrease the bleeding time after in vivo injuries while decreasing the interleukin concentration too [35]. Interestingly, pEVs have been used after being stored at −20 • C, proving to maintain the positive effects for hemorrhagic shock treatment and easing their use [33], thus being an attractive alternative to liquid platelet-rich plasma preparations that need to be kept at temperatures of 20-24 • C and with a short half-life (approximately 5 days) [34,50].…”

“…These effects may be related to the pEVs cargo, which was positive in different growth factors, including platelet-derived growth factor (PDGF), basic fibroblasts growth Regenerative applications of platelet-derived extracellular vesicles (pEVs). Main regenerative effects reported for pEVs in regenerative fields, including injuries [30][31][32][33][34][35][36], biomaterials [30,31], neurogenesis [37,38], muscle regeneration [39], angiogenesis [37,38,[40][41][42], bone regeneration [25,26,[43][44][45] and osteoarthritis [46][47][48][49] and the major reported therapeutical effects. This figure was created using Freepik images.…”

“…Furthermore, in addition to the wound healing properties, two rat model studies suggest that pEVs prevent uncontrolled blood loss and hemorrhagic shock [33][34][35]. In fact, the pEVs dose-response performed in vitro suggests that pEV blood coagulation is dependent on EVs concentration [33], as the International Society for Extracellular Vesicles (ISEV) encourages to test [1].…”

Platelet-Derived Extracellular Vesicles for Regenerative Medicine

“…Furthermore, in addition to the wound healing properties, two rat model studies suggest that pEVs prevent uncontrolled blood loss and hemorrhagic shock [20][21][22]. In fact, the pEVs dose-response performed in vitro suggests that pEV blood coagulation is dependent on EVs concentration [20], as the International Society of Extracellular Vesicles (ISEV) encourages to test [1].…”

“…Even more, pEVs have an effect on endothelial permeability, which mitigates blood loss too [21]. Further studies report that aggregates of thrombin activated pEVs decrease the bleeding time after in vivo injuries while decreasing the interleukin concentration too [22]. Moreover, it is important to realize that pEVs are also involved in the inflammatory response.…”