This proposal addresses the topic area of congenital heart disease. Congenital heart disease often requires extensive corrective cardiac surgery. During these surgeries, patients are placed on cardiopulmonary bypass (CPB), which can cause extensive bleeding complications. The underlying causes of these bleeding problems are multifaceted but involve dilution of clotting proteins and platelets. Platelets are blood cells that play a large role in cessation of bleeding following injury. Platelets are activated at injury sites, which allows them to bind clotting proteins, thereby stabilizing the developing clot. Over time, platelets contract clots, which further stabilizes the network. Our group has recently developed synthetic platelet-like particles (PLPs), which are capable of recapitulating a number of features of natural platelets, including binding specifically to fibrin, the major protein constituent of clots, augmentation of clotting, and clot contraction over time following clot formation. We aim to further develop these PLPs for treatment of bleeding following cardiac surgery to facilitate their translation into a clinically viable product. This proposal will specifically address optimization of PLP formulation and subsequently will characterize the ability of PLPs to decrease bleeding times in animal models that mimic the bleeding problems associated with CPB. Specific emphasis will be placed on characterizing the safety of PLPs. If successful, these PLPs could greatly improve treatment options for post-surgical bleeding as well as other bleeding disorders.