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Validation pré-clinique d'un produit d'ingénierie vasculaire à base d'hydrogel de chitosane

Abstract : Aims. Vascular grafts made of synthetic polymers perform poorly in small-diameter applications. Consequently, there is strong clinical to produce small caliber vessels with better patency. The emergence of vascular engineering opens new possibilities. Chitosan, a natural polymer, can provide a scaffold for vascular engineering. The goal of this thesis was to produce chitosan-based hydrogels and to assess their biological and mechanical properties and their biointegration. Methods and Results. Hydrogels were mechanically characterized in vitro. By increasing chitosan concentration, suture retention value, average burst strength and elastic moduli increased significantly. A series of experiments ranging from in vitro biocompatibility tests to in vivo studies was performed. In vitro, chitosan supported human endothelial progenitor cells (EPCs) proliferation and was hemocompatible. In vivo, no resorption of chitosan was observed in a rat heterotopic implantation model. In addition biointegration of chitosan hydrogels were investigated. In vitro, chitosan endothelialized with EPCs behave as a native endothelium. In vivo, chitosan hydrogels were able of modulating the inflammatory response of injured host tissue by favouring polarization of macrophages towards the beneficial M2 phenotype in a rat ectopic implantation model. Finally, as a proof of concept, 2 chitosan tubes were implanted successfully as carotid interposition grafts for 3 days in sheep. Conclusion. By modulating chitosan concentration, we produced scaffolds with suitable properties to be implanted in vivo.
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https://tel.archives-ouvertes.fr/tel-01724107
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Submitted on : Tuesday, March 6, 2018 - 10:19:07 AM
Last modification on : Friday, October 23, 2020 - 5:03:25 PM
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Audrey Biscay-Aussel. Validation pré-clinique d'un produit d'ingénierie vasculaire à base d'hydrogel de chitosane. Médecine humaine et pathologie. Université de Bordeaux, 2017. Français. ⟨NNT : 2017BORD0819⟩. ⟨tel-01724107⟩

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