Résumé

In bypass graft surgery, surgeons have turned to synthetic materials such as polyethylene terephthalate (Dacron) and expanded polytetrafluoroethylene (ePTFE) when lacking sufficient and suitable arteries or veins for the procedure. However, due to their low patency in small-caliber bypass surgery (<6 mm), research has been focused to incorporate several anti-inflammatory and anti-coagulant agents in prosthetic grafts. Nitric oxide (NO) has been incorporated in blood-contacting medical devices because of its anti-platelet and anti smooth muscle cell proliferation properties. In the scope of this project, NO has been incorporated into a range of commercial polydimethylsiloxane-based polyurethanes (Elast-eon® 2, Aortech, Australia), using a technique not reported before, that consists of forming the NO donors in situ within polymer films. Elast-eon® polyurethanes (PU) with different mass percentages of polydimethylsiloxane (PDMS) in their soft segment were doped with secondary amines (linear polyethylenimine, LPEI), and films formed by solution casting and solvent evaporation. To determine the suitability of these novel NO released materials, potential leaching of secondary amines was assessed by LPEI quantification through ninhydrin assay. LPEI-doped PU films were subsequently reacted with NO in a reaction chamber to form diazeniumdiolates, NO releasing precursors. Also to assess if the incorporation of LPEI and NO gassing step alter the mechanical properties of the films, strain-stress characteristics were assessed by tensile testing after each modification step. Finally, initial attempts were made to incorporate LPEI into Elast-eon® porous grafts with welldefined porosity. LPEI leaching and NO elution from these porous grafts were also assessed. Elast-eon® films doped with LPEI50 (22,000 g/mole) and LPEI500 (220,000 g/mole) were successfully made by solution casting and solvent evaporation. LPEI50 and LPEI500 leached at a suitable rate that would reduce potential adverse effects to the host. NO gassing of polyurethane (PU) films with incorporated LPEI (PULPEI films) successfully formed the desired NO donors (NONOates), and the PU-LPEI films showed significant release of NO and in concordance with the hypothesis of the study, the NO release from PU-LPEI50 films demonstrated that polydimethylsiloxane (PDMS) soft segments increases the permeability of the polymer matrix. Thus the total NO release was higher for polymer films with high percentage of PDMS. Also, a stressstrain characterization demonstrated that the mechanical properties of the films were not unduly affected by either NO gassing or LPEI incorporation. Finally, LPEI50 was successfully incorporated into a porous Elast-eon® vascular graft scaffold using the swelling properties of the polymer. Because of the enhanced surface to volume ratio and diffusion due to the porosity, the NONOate groups in the porous grafts decomposed much faster than in the films, resulting in the release of most of the nitric oxide after 1 day. This pilot study does provide proof of concept. It was possible to form NONOates in situ because of a high PDMS content polymer matrix. However, to apply this concept on porous graft capable of sustained NO-release, further work will be required on this technology with amines that are i) better-retained in the matrix due to increased hydrophilicity or covalent binding, and ii) capable of forming more stable NONOates

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