Fe-based bioresorbable alloy 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 optimised mechanical and biodegradation properties together with limited thrombogenicity. Fe-based alloys are amongst the good candidates. Blood compatibility of a new Fe-based alloy was studied in vitro via assessment of haemolysis and platelet activation. Human whole blood was incubated for 60 min with either the Fe-based alloy or the cobalt-chromium (Co-Cr) alloy composing bare metal stents. After centrifugation, optical density of the supernatant was measured at 540 nm and the amount of haemolysis was calculated. For platelet activation assays, human or rat washed platelets were incubated for 60 min with both alloys before measuring their reactivity to platelet agonists by flow cytometry, using CD62P and activated α2bβ3 antibodies. In addition, phosphorylation of PKC substrates was evaluated by western blot. No significant red cells haemolysis was induced by both alloys (0.5 and 0.3% respectively). In addition, Co-Cr alloy did not affect CD62P exposure and α2bβ3 activation at platelet surface upon thrombin (0.03 to 0.3 U/ml) stimulation. In contrast, Fe alloy completely abolished their response to the agonist. A drastic inhibition of the phosphorylation state of PKC substrates was also observed after activation with thrombin, collagen (1.25 to 5 μg/ml) and ADP (0.1 to 10 μM). Since similar inhibitory effects were obtained when using a conditioned-reaction medium previously incubated with this Fe alloy, we postulate that its biocorrosion might release components counteracting platelet activation. The Fe-based resorbable scaffold displays anti-thrombogenic properties and is a promising platform for next-generation stent technologies.