Platelet-inspired nanomedicine in hemostasis thrombosis and thromboinflammation

Platelets are anucleate cell-fragments derived predominantly from megakaryocytes in the bone marrow and released in the blood circulation, with a normal count of 150 000-40 000 per microl and a lifespan of approximately 10 days in humans. A primary role of platelets is to aid in vascular injury site-specific clot formation to stanch bleeding, termed hemostasis. Platelets render hemostasis by a complex concert of mechanisms involving platelet adhesion, activation and aggregation, coagulation amplification, and clot retraction. Additionally, platelet secretome can influence coagulation kinetics and clot morphology. Therefore, platelet defects and dysfunctions result in bleeding complications. Current treatment for such complications involve prophylactic or emergency transfusion of platelets. However, platelet transfusion logistics constantly suffer from limited donor availability, challenges in portability and storage, high bacterial contamination risks, and very short shelf life (~5 days). To address these issues, an exciting area of research is focusing on the development of microparticle- and nanoparticle-based platelet surrogate technologies that can mimic various hemostatic mechanisms of platelets. On the other hand, aberrant occurrence of the platelet mechanisms lead to the pathological manifestation of thrombosis and thromboinflammation. The treatments for this are focused on inhibiting the mechanisms or resolving the formed clots. Here, platelet-inspired technologies can provide unique platforms for disease-targeted drug delivery to achieve high therapeutic efficacy while avoiding systemic side-effects. This review will provide brief mechanistic insight into the role of platelets in hemostasis, thrombosis and thromboinflammation, and present the current state-of-art in the design of platelet-inspired nanomedicine for applications in these areas.