Thrombogenicity Reduction by Means of Surface Structures – A combined In-silico and In-vitro study – ThromboSurf

Several treatments of cardiovascular diseases involve artificial heart valves, ventricular assist devices, grafts, or stents, which are all blood-contacting medical devices. The haemocompatibility of medical devices remains the major challenge in their development. An insufficient haemocompatibility may lead to thrombus (blood clot) formation, failure of the device and in the worst case to the patient’s death. When a foreign material comes in contact with blood, a foreign body reaction is initiated: proteins adsorb on the surfaces and in consequence, the coagulation cascade is triggered, circulating platelets are activated and recruited, possibly leading to clotting and thrombus formation at the foreign material. Although an anticoagulation therapy can counteract these adverse events, it bears the risk of severe bleeding complications. Hence, improving the haemocompatibility of blood-contacting artificial materials is the key for better and safer medical devices. The strategy often put forward to increase haemocompatibility, with limited success, is to reduce the protein adsorption to prevent the triggering of the coagulation cascade, a series of enzymatic reactions leading to the formation of fibrin from the fibrinogen present in plasma. Since surface-related thrombi are most often rich in platelets, the main working assumption of ThromboSurf is that another strategy is worth investigating to reduce the artificial surface thrombogenicity: controlling the capability of the platelets to adhere to the surface by adjusting the flow above the surface. To manipulate thrombotic adverse reaction and increase haemocompatibility, surface topographies in the nano/micrometre range have gained attention as a promising biomimetic approach. However, only incomplete, and inconsistent results regarding effective structure geometries and dimension were published so far, leaving the full potential and impact of surface structures unclear. The aim of the project is thus to investigate the relationship between platelet adhesion and microstructured surfaces, specifically designed to alter the near-wall flow, through in silico and in vitro approaches. We will use intensive computational fluid dynamics and particle-based platelets models, high-throughput real-time cell imaging and in vitro blood tests to derive a correlation between alterations in haemodynamics by surface structure and the resulting platelet activation and adhesion. The in silico model will first be improved and tuned iteratively, until the prediction of platelet-surface interactions is precise. Then, the model will be applied to many different surface structures to create a database including surface properties and platelet responses. This broad physical cross-analysis will be unique and provide a base for distinct surface topography research in the light of thrombogenicity reduction. A subset of promising topographies will be selected and investigated experimentally in vitro to confirm the thrombogenicity outcome. Additionally, the impact of complex flow conditions such as pulsatility and turbulence effects, which occur in blood-contacting medical devices regularly, will be considered, paving the way for future breakthroughs in the use of haemocompatible artificial surfaces.