Amélioration des qualités fonctionnelles des implants à destinée vasculaire
|Advisor:||Laroche, Gaétan; Petitclerc, Éric|
|Abstract:||The overall objective of this Ph.D. thesis is to improve the patency of PTFE vascular prostheses. To achieve this goal, two strategies were developed: one aiming to decrease thromboses risks and the other to inhibit intimal hyperplasia. Thromboses happen in synthetic prostheses because they are made of non-haemocompatible materials. Since the only known haemocompatible tissue is the endothelium (monolayer of endothelial cells covering the inner wall of all blood vessels and heart), the PTFE was modified in order to promote adhesion and survival of endothelial cells. PTFE was first functionalized by low pressure ammonia plasma to introduce amino groups and linking arms were grafted onto these functional groups. Two different linkers were used, glutaric anhydride (GA) and sulfo-SMPB (SMPB). The free end of linking arms was used to graft fibronectin (FN), an adhesion protein found in most extracellular matrix. The success of each step of modification was ascertained by XPS analyses. FN quantity, activity and conformation on each linking arm was studied by radiolabeling assays, cellular adhesion assays, ELISA, AFM and contact angle. FN greatly promotes endothelial cell adhesion on PTFE, especially when it is grafted onto GA. It was demonstrated that FN grafted on GA had a better biological activity and a more unfolded conformation than FN grafted on SMPB. Intimal hyperplasia is a thickening of the innermost layer of artery wall due to migration and proliferation of smooth muscle cells and their matrix production. This thickening leads to a decrease in lumen size and blood flow which ultimately cause the prosthesis failure. To counter this phenomenon, the inhibition potential of imatinib mesylate over smooth muscle cells and its harmlessness to endothelial cells were evaluated in vitro. Proliferation assays of muscular and endothelial cells were performed in mono and co-culture with different imatinib mesylate concentrations. It was demonstrated that imatinib mesylate inhibits smooth muscle cells and promotes endothelial cell proliferation in a concentration range of 1.2 to 3.7µM. Furthermore, PARP and cleaved caspase 3 expression analyses by western blotting showed that in this concentration range, imatinib mesylate did not cause cell apoptosis.|
|Document Type:||Thèse de doctorat|
|Open Access Date:||16 April 2018|
|Collection:||Thèses et mémoires|
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