Recouvrements à base de dextrane pour applications médicales

Authors: Michel, Eléonore
Advisor: Mantovani, D.; Letourneur, François
Abstract: The last decades have witnessed the remarkable growth of biomaterial science and engineering field, especially for cardiovascular applications, for which devices have evolved from simple material to complex structures. This development has stemmed from the necessity for biomaterials to exhibit different properties, related to their function, which are not always inherently compatible. Historically, the first materials selected for medical devices conception were the ones exhibiting the best compromise between all the physicochemical, mechanical and biological requirements. Nevertheless, while physicochemical and mechanical properties are often handily combined, the development of materials which also possess suitable biological properties have proved to be much more challenging, leading to clinical complications. Surface modification represents a valid solution to improve the biological performances of medical devices while maintaining the bulk properties of the material. Biomaterial coatings may modulate the biological response at the biomaterial-host interface and decreases the undesirable effects. Coatings have been optimized in regards to two main aspects: the biological response and the mechanical response. For the biological response, the two main approaches consist in 1) inducing cell adhesion, proliferation or migration with pro-active coatings and 2) using inert material, mostly, and avoiding the adhesion of any biological components with passive coatings. In certain cases, it is interesting to be able to favor particular cells and to limit others, for example to avoid restenosis, which is mostly due to the uncontrolled proliferation of smooth muscle cells leading to the re-obstruction of the artery, after stent implantation. So, researchers’ aim are stent coatings capable of limiting this cell proliferation along with facilitating the re-endothelialization, which means allowing the adhesion and the proliferation of endothelial cells. In other cases, it is interesting to obtain surfaces limiting any cell adhesion, as for catheter use. Depending on their function, catheters should be able to avoid cell adhesion, in particular bacteria adhesion that leads to infections, and to be hemocompatible, particularly in the vascular field. Previous studies showed that a copolymer made of dextran and poly(butyl methacrylate) (PBMA) demonstrated such biological properties and a good resistance to deformation, which is an important parameter related to the deformation implied in a stent implantation. In this project, the approach was to use this copolymer as a stent coating and to increase its adhesion to surface by providing covalent bonds with the surface. To do so, the dextran part of the copolymer firstly needed to be activated in order to be grafted to the surface. Thus, it was important to ascertain the influence of the multiple modifications on the biological and mechanical properties of the resulting materials at each step, but also towards a chemical point of view, the influence that these modifications may have on the subsequent copolymerization. Firstly, only dextran has been considered and was modified by oxidation and carboxymethylation reactions and grafted to fluorocarbon surfaces. Physicochemical analyses were used to validate a way of dextran modification which allowed the grafting without hindering the subsequent copolymerization. The modification by carboxymethylation led to a better surface coverage and kept the polysaccharide’s structure. Then, the grafting of carboxymethyl dextran (CMD) was optimized according to different degrees of modification, also considering the influence these modifications could have on biological properties. Finally, the previous studied CMD, with defined biological properties, were copolymerized with butyl methacrylate monomers (BMA). The resulting copolymers were then characterized by physicochemical, biological and mechanical analyses. Preliminary results showed that copolymers films were anti-adhesive to cells, which allowed to find new applications to the project. Elastic and anti-adhesive properties of the CMD-co-PBMA copolymers films, make them particularly interesting for catheter coatings application.
Document Type: Thèse de doctorat
Issue Date: 2016
Open Access Date: 24 April 2018
Grantor: Université Laval
Collection:Thèses et mémoires

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