Towards new therapies for endovascular revascularization procedures

Surgical revascularization by either natural or synthetic grafts, as well as less invasive percutaneous transluminal angioplasty (PTA), with or without stent implantation, is currently used in the treatment of vascular diseases. Despite its less invasive nature, stent implantation remains limited by in-stent restenosis within the stent struts. Although systemic administration of therapeutic drugs has shown disappointing results, the local delivery or presentation of therapeutic molecules/drugs/genetic material is a promising area for development.; The work that forms the basis of this thesis attempts to develop new devices or new strategies to achieve more efficient delivery of therapeutic biomacromolecules to the vascular walls during revascularization procedures. The work can be divided into three 3 Parts: (I) Modification of endovascular stents by hybrid coatings: two strategies involved the surface modification of the devices by plasma polymerization, followed by covalent immobilization of hyaluronan conjugated or able to be conjugated with a bioactive component (peptides/proteins or radionuclides). The last section of the Part I described the development of bioactive coating based on the Layer-by-Layer self-assembly of polysaccharide multilayers. (II) Development of a biodegradable membrane-covered stent: A chitosan-PEG blend has been used to engineer a biodegradable membrane-covered device for endovascular procedures. This membrane-covered device was able to sustain physiologic pressure, showed very small water permeability, displayed an appropriate haemocompatibility and could be used for drug delivery. (III) Development of nanocoatings to be self-assembled in situ onto the vascular wall: self-assembled multilayers have been investigated to protect damaged arteries and to control the healing processes by efficiently delivering therapeutic biomolecules to the vascular wall. These nanometric coatings have been deposited onto blood vessel by the Layer-by-Layer technique and have shown great potential for drug delivery of various macromolecules such as NO-donor or plasmid DNA.