Synthèse et caractérisation d'un hydrogel d'alginamide pour la régénération de voies nerveuses lésées au sein du Système Nerveux Central chez le rat

Abstract : The aim of this work was to synthesise alginate hydrogels, stable in time, and to evaluate their potential use as scaffolds for the damaged nerve regeneration in central nervous system. Various amphiphilic derivatives of sodium alginate were prepared by covalent attachment of alkyl chains (12 carbons) onto the polysaccharide at different substitution ratio, either via ester (alginate ester) or amide (alginamide) linkages, these last ones being more stable toward hydrolysis. The properties in solution of the alginamide derivatives were studied in terms of solubility, stability as function of time, rheological behaviour and swelling ratio. Results were compared to those obtained with the alginate ester family and highlighted a different behaviour for the alginamide series in semi-dilute regime. In particular, alginamide hydrogels exhibited a low critical strain which has been attributed to the presence of aggregates in the solution. The formation of these aggregates was due to the occurrence of a secondary cross-linking reaction during the synthesis of polymers. Nevertheless, it was possible, by appropriate tuning of the substitution yield and of the solution concentration, to obtain a three-dimensional network stabilized by intermolecular hydrophobic interactions, which has been evaluated as regenerative support for the considered application. In vivo studies demonstrated the absence of nerve regeneration for the tested injured animals after one year. However, these studies allowed us to evaluate both the strategy for the implantation of a physical gel exhibiting a shear-thinning and thixotrope behavior and the possibility to encapsulate a pharmacological treatment. An enlarged project specification has also been defined for this biomaterial (pH, stability, swelling ratio)
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Frédéric Vallée. Synthèse et caractérisation d'un hydrogel d'alginamide pour la régénération de voies nerveuses lésées au sein du Système Nerveux Central chez le rat. Autre. Institut National Polytechnique de Lorraine, 2007. Français. ⟨NNT : 2007INPL110N⟩. ⟨tel-01752836⟩

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