Files

Abstract

Coronary artery disease is one of the main causes of death in western countries. The standard of care has become the implantation of a coronary stent, i.e. a small metal-mesh tube reopening the lumen of the artery and maintaining the blood flow to the heart muscle. Drug eluting stents (DES) consist of a metal substrate coated by a polymer matrix containing the drug. These immunosuppressive or antiproliferative agents diffuse through the coating into the artery tissue to prevent restenosis – the renarrowing of the artery. The aim of this project is the development of the next generation of coating for DES implants. Composed of a ceramic, the new coating will offer several advantages over polymers in terms of biocompatibility, safety and efficacy of the drug delivery. A multi-step process is used to produce the ceramic coating. First, polymeric templates are deposited on the metallic substrate. Secondly, they are covered with a ceramic layer. Then, during a sintering step, the coating is consolidated and templates are removed, resulting in the creation of reservoirs. Finally, the coating is loaded with a drug by dipping the sample into a solution containing the active molecule. This structured coating combines two types of porosity: a macro-sized porosity used as drug reservoirs and a mesoporosity controling the drug diffusion. This work was mainly focused on the coating structuration and its mechanical stability. A Titanium ceramic coating was successfully structured with 1-micrometer templates and deposited on a 316L substrate. A thermal treatment was applied to densify the coating and to enhance its mechanical stability during stent proceeding. A test was selected and applied on the coating in order to quantify the cohesion and adhesion properties of the coating. To enhance the statistical representativity a phenomenological model has been used to analyse the results. Different sintering processes of the coated samples and their mechanical characterization have followed these steps. Finally, different synthesis routes were tested in order to enhance the technology. Inkjet technique was used to create a structured ceramic coating on stents. Also, sol-gel chemistry was used to synthesis the ceramic coating. An alternative ceramic coating was obtained with an important mesoporosity. Additionally, in order to increase the drug loading ability, templates of 5 micrometers were successfully used to structure the coating. Very promising results were obtained. First, it was observed that coating was highly cracked, with the strain. Moreover, it was shown that no delamination could be observed if the atmosphere was not oxidative. Otherwise, coatings were delaminated due to tangential compressive stress in the coating. In general it was observed that the porosity was important to avoid an important increase of the compressive stress in the coating, due to particles facing, which could lead to an important shear stress at the interface and thus to a delamination of the coating. In addition, it was observed that the fragmentation method, and its improvement, is working only for dense coating. Finally, different proof of concepts were done on stent coated by inkjet, alternative coating synthesis by sol-gel and on the increase of the drug loading capacity thanks to different structuration methods.

Details

Actions