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Biocompatibility improvement conferred by the immobilization of a CD31 peptide on endovascular stents

Abstract : Over the last decades, coronary stents and intracranial flow diverting stents have revolutionized the endovascular treatment of two different arterial pathologies: coronary artery disease and intracranial aneurysms. The working mechanisms of these metallic endoprostheses are different but both are associated with complications stemming from biocompatibility issues. In particular, the rapid covering by endothelial cells presenting an anti-inflammatory and anti-thrombotic phenotype is key to the integration of the endoprosthesis at the blood/vessel interface. Thus, the development of solutions to improve the endothelialization and the integration of these two types of stents in the vessel wall would represent a major progress in their respective field.In this context, this thesis work deals with the immobilization of a bioactive molecule on coronary stents and flow diverting stents in order to solve their biocompatibility issues. The bioactive molecule that we used is a synthetic peptide, named P8RI, which promotes the regulatory functions of the transmembrane glycoprotein CD31 : the inhibition of platelets and leukocytes activation, as well as the enhancement of endothelial cell survival, migration and barrier function.The first part of this thesis work consisted in the development of a process for the immobilization of P8RI on metallic stents. We adopted three successive approaches: the direct immobilization of the peptide on plasma-functionalized alloy surfaces; the plasma-enhanced chemical vapor deposition of an intermediate polymeric layer; and the deposition of a polydopamine coating by self-polymerization, followed with the immobilization of a linker and the binding of P8RI by copper-free click chemistry.We then carried out an in vitro evaluation of the biocompatibility of the resulting coated alloy surfaces, in terms of anti-thrombotic, anti-inflammatory, and pro-endothelialization properties. The surfaces on which P8RI had been immobilized were shown to exhibit a tendency to decrease platelet adhesion, increase endothelial cell adhesion and barrier function, and promote an anti-inflammatory and anti-thrombotic phenotype in human vascular endothelial cells.Finally, coronary stents and flow diverting stents were evaluated in vivo. Coronary stents were implanted in the coronary arteries of farm pigs, and preliminary results showed a more complete endothelialization and a lesser density of adherent leukocytes on ‘P8RI-coated’ stents than on the controls. ‘P8RI-coated’ flow diverting stents were implanted in a rabbit elastase-induced carotid aneurysm model. Compared with the controls, they were associated with the formation of a thicker and better organized neointima, in particular on the stent struts in front of the aneurysm neck, which implies lesser risks of persistence of blood flow and aneurysm rupture.
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Submitted on : Monday, December 2, 2019 - 3:49:06 PM
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  • HAL Id : tel-02385280, version 1

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Charlotte Rasser. Biocompatibility improvement conferred by the immobilization of a CD31 peptide on endovascular stents. Biochemistry, Molecular Biology. Université Sorbonne Paris Cité, 2017. English. ⟨NNT : 2017USPCC317⟩. ⟨tel-02385280⟩

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