In vitro characterization of SynthoPlate™ (synthetic platelet) technology and its in vivo evaluation in severely thrombocytopenic mice.
Essentials Platelet transfusion suffers from availability, portability, contamination, and short shelf-life. SynthoPlate™ (synthetic platelet technology) can resolve platelet transfusion limitations. SynthoPlate™ does not activate resting platelets or stimulate coagulation systemically. SynthoPlate™ significantly improves hemostasis in thrombocytopenic mice dose-dependently.


SUMMARY
Background Platelet transfusion applications face severe challenges, owing to the limited availability and portability, high risk of contamination and short shelf-life of platelets. Therefore, there is significant interest in synthetic platelet substitutes that can provide hemostasis while avoiding these issues. Platelets promote hemostasis by injury site-selective adhesion and aggregation, and propagation of coagulation reactions on their membranes. On the basis of these mechanisms, we have developed a synthetic platelet technology (SynthoPlate™) that integrates platelet-mimetic site-selective 'adhesion' and 'aggregation' functionalities via heteromultivalent surface decoration of lipid vesicles with von Willebrand factor-binding, collagen-binding and active platelet integrin glycoprotein (GP) IIb-IIIa-binding peptides. Objective To evaluate SynthoPlate for its effects on platelets and plasma in vitro, and for systemic safety and hemostatic efficacy in severely thrombocytopenic mice in vivo. Methods In vitro, SynthoPlate was evaluated with aggregometry, fluorescence microscopy, microfluidics, and thrombin and fibrin generation assays. In vivo, SynthoPlate was evaluated for systemic safety with prothrombin and fibrin assays on plasma, and for hemostatic effects on tail-transection bleeding time in severely thrombocytopenic (TCP) mice. Results SynthoPlate did not aggregate resting platelets or spontaneously promote coagulation in plasma, but could amplify the recruitment and aggregation of active platelets at the bleeding site, and thereby site-selectively enhance fibrin generation. SynthoPlate dose-dependently reduced bleeding time in TCP mice, to levels comparable to those in normal mice. SynthoPlate has a reasonable circulation residence time, and is cleared mostly by the liver and spleen. Conclusion The results demonstrate the promise of SynthoPlate as a synthetic platelet substitute in transfusion treatment of platelet-related bleeding complications.
['Shukla|M|M|', 'Sekhon|U D S|UD|', 'Betapudi|V|V|', 'Li|W|W|', 'Hickman|D A|DA|', 'Pawlowski|C L|CL|', 'Dyer|M R|MR|', 'Neal|M D|MD|', 'McCrae|K R|KR|', 'Sen Gupta|A|A|']
D000818:Animals D001760:Bleeding Time D001777:Blood Coagulation D001792:Blood Platelets D001802:Blood Substitutes D006470:Hemorrhage D006487:Hemostasis D006801:Humans D008027:Light D051379:Mice D044085:Microfluidics D008855:Microscopy, Electron, Scanning D008856:Microscopy, Fluorescence D010973:Platelet Adhesiveness D017713:Platelet Transfusion D012542:Scattering, Radiation D013917:Thrombin D013921:Thrombocytopenia
platelets platelet transfusion hemostasis bleeding time thrombocytopenia