Contrôle de la dégradation de stents biorésorbables via une stratégie de surface innovante

Ischemic heart disease is the leading cause of death worldwide. Bioresorbable stents offer a promising treatment to provide temporary vascular support before completely degrading, which can widen the narrowed artery and avoid late period thrombosis. Iron-based stents were explored as attractive candidates for their superior mechanical properties and good biocompatibility. However, their clinical application has been hindered by the extremely low degradation rate of iron-based materials. Moreover, recent studies have demonstrated that toxic reactive oxygen species (ROS) are generated during iron degradation under physiological conditions, and their production increases with the degradation rate. These ROS can lead to oxidative stress, damage the cellular components and cause toxicity. Although various chemical strategies have been reported to enhance the corrosion rate of Fe, no studies have yet investigated approaches that simultaneously promote increased corrosion rate and reduced ROS production. In this work, we address these intertwined challenges by developing an innovative surface strategy that enhances Fe corrosion while mitigating ROS production. The resulting modified surface was fully characterized by scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS), immersion tests, electrochemical analysis and in vitro studies. Moreover, the modified surface was successfully post-functionalized with an antioxidant drug. The main content of this PhD work can be divided into several parts, as follows: (1) The first part is dedicated to a survey of the literature on the development of cardiovascular stents and particularly on the main strategies developed so far to design Fe-based stents with accelerated degradation, highlighting the fundamental mechanisms of corrosion. (2) The second part is devoted to the design of a novel surface modification strategy based on the in-situ co-reduction of chloroauric acid and aryl diazonium salt (4-cyanobenzene diazonium tetrafluoroborate, DCN), acting as a coupling agent to attach gold nanoparticles on the surface of Fe materials. The results emphasize the key role of the Au-based nanocoating to initiate microgalvanic corrosion and enhance the corrosion rate of Fe. Interestingly, the Au NPs serve as catalysts for oxygen reduction reaction, changing the 2e- transfer pathway to 4e- transfer pathway, thereby decreasing the ROS production. (3) The third part investigates the possibility to extend this breakthrough strategy to laser-cut prototype stents. The fabrication procedure, including annealing, pickling and electropolishing, was explored to optimize the stent mechanical properties and obtain an optimal surface for post-modification. The results showed that the modified prototypes exhibit an enhanced corrosion rate and degradation lifespan of approximatively 12 months. In addition, an improved biocompatibility was observed through cell culture tests. (4) The last part of this PhD work aimed to enhance the performance of Au NPs-coated Fe stents for clinical applications through post-functionalization. N-Acetylcysteine (NAC) was utilized as a model compound due to its antioxidative effect for ROS scavenging in clinical studies. As a preliminary study, NAC was grafted on colloidal Au NPs, rather than directly on the Au-coated stent surface, via a thiol-yne click chemistry method, using an appropriate diazonium salt (4-ethynylbenzenediazonium tetrafluoroborate, DCC). The results showed that the NAC-functionalized Au NPs preserved the NAC antioxidant properties, offering promising features for clinical applications of Au-coated Fe stents.