(426c) Enhancing Clot Formation and Mechanical Strength with Graphene / Peg Hemostatic Nanoplates

For those under the age of 44, as well as those serving in the armed forces, trauma (blast or blunt) is the main cause of mortality. A number of methods have been proposed to effectively halt bleeding from external wounds. Nonetheless, dealing with internal bleeding is complicated. When an injury occurs, hemostasis (the natural clotting mechanism) begins to stop the bleeding and start the recovery process. However, many patients suffering from lethal internal injuries decease from severe blood loss while being transferred to the hospital and before even reaching the emergency room where they can be treated by surgeons. An effective approach would be the development of synthetic hemostatic formulations that could be administered by paramedics during a patient's transport to the hospital and reduce blood loss, by augmenting the natural clotting mechanism and leading to faster formation of clots.

In the natural clotting mechanism, fibrinogen binds to activated platelets and crosslinks those. Most studies have thus been focused on enhancing hemostasis by interacting activating platelets integrins (GPIIb/IIIa) withfibrinogen-derived peptides (either from the α- or the γ-chain) that are conjugated to either liposomes or polymer-based nanoparticles. A second major concern expressed by surgeons regards the stability of clots post formation, especially when are under mechanical stress and blood flow. Graphene oxide (GO) has been used in a variety of biomedical applications due to its large surface area and mechanical properties. Aiming to provide dual hemostatic ability upon interaction with activated platelets as well as to augment the fibrin clot strength and durability upon integration, we are developing a ~300-500 nm nanographene-based hemostat. The nanoGO/PEG material is functionalized with two peptides from both the α-chain and the γ-chain of fibrinogen, offering interaction with activated platelets at two binding sites. The material is evaluated in vitro with human blood platelets activated with ADP and collagen for platelet plug enhancement / reduction in bleeding time (clotting acceleration) over controls, and ex vivo for mechanical enhancement of blood clots (tensile stretching); next, it will be evaluated in vivo with a lethal injury animal model after intravenous administration.