Fe-based alloy for stent application inhibits platelet activation

Abstract

Bioresorbable polymer stents have been used to provide a transient scaffold after coronary angioplasty. However, an increase in stent thrombosis has been observed. A current challenge is thus to develop new bioresorbable stents combining optimized mechanical and biodegradation properties together with limited thrombogenicity. In this context Fe-based alloys are amongst the good candidates for stent manufacture. We aimed to explore in vitro blood compatibility of a new Fe-based alloy. Human whole blood was incubated for 60 min with either the Fe-based alloy, pure iron, cobalt-chromium (CoCr) alloy (composing the bare metal stent used as a reference) or magnesium (Mg) alloy (composing a bioresorbable stent newly on the market). After centrifugation, haemolysis was calculated based on the optical density (540 nm) of the supernatant. For platelet activation assays, human washed platelets were incubated for 60 min with each metal before measuring their reactivity to a platelet agonist by flow cytometry, using CD62P and PAC-1 antibodies. In addition, phosphorylation of PKC substrates was evaluated by western blot. None of the alloys induced significant red cells haemolysis. In addition, Co-Cr did not affect CD62P exposure and PAC-1 presence at platelet surface upon thrombin (0.03 to 0.3 U/ml) stimulation. In contrast, Fe-based alloy and pure iron decreased significantly platelet response to agonist, as well as Mg but to a lesser extent. A drastic inhibition of the phosphorylation state of PKC substrates was also observed with the Fe-based alloy after activation with thrombin. Since similar inhibitory effects were obtained when using a conditioned-medium (incubated for 60 min with the alloy), we postulated that its bio-corrosion might release components counteracting platelet activation. The Fe-based alloy seems to be a promising platform for next-generation stent technologies.