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Supramolecular gels: synthesis, self-assembly, biocompatibility and application as scaffold for neuronal cell culture

Abstract : Nowadays, repairing brain lesions is still one of the main challenges of tissue engineering. Meanwhile, work still has to be done for the creation of representative in vitro brain tissue models, especially when it comes to the biomaterials used to support cell growth. This present work consists in the development of a hydrogel as a biomaterial for the survival and growth of human neural stem cells. These (supra)molecular gels, the property of which is to form by self-assembly, may present many advantages for this kind of application. Indeed, their mechanical properties, their bioavailability and their microstructure – among others – make them interesting candidates for neuron culture. One family of supramolecular gelators have thus been synthesized, characterized and tested as cell culture scaffolds. Those gelators are alkylgalactonamides, which means they are derived from a sugar – the galactose – and an alkyl fatty chain. They form hydrogels by cooling down to room temperature after a first dissolution at high temperature. The cooling provokes the self-assembly of the molecules resulting in the formation of the fibers. During their preparation, it has been found that a controlled cooling rate enabled the formation of more homogeneous and more stable hydrogels that are compatible with cell culture conditions and with longer fibers. These hydrogels have shown a good biocompatibility as well as a good cell survival and a three-dimensional growth of human neural stem cells. The latter grew long neurites and expressed markers of neuronal (β3-tubulin) and glial differentiation (GFAP), especially on one of the hydrogels. The last part of this work was to use new 3D material structuring techniques in order to further construct well-defined centimetric scaffolds with these hydrogels. A technique of wet spinning based on solvent exchange was developed and enabled the direct and controlled extrusion of the hydrogel at room temperature. Thin and regular hydrogel filaments composed of monodisperse nanometric fibers can thus be obtained. Trials have also been done to apply this method to 3D printing. In the end, this project shows that some molecular gels can display properties particularly adapted for tissue engineering, especially with neural stem cells, and it also opens perspectives for the shaping of these delicate materials.
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Submitted on : Monday, April 15, 2019 - 9:52:09 AM
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Anaïs Chalard. Supramolecular gels: synthesis, self-assembly, biocompatibility and application as scaffold for neuronal cell culture. Micro and nanotechnologies/Microelectronics. Université Toulouse 3 Paul Sabatier (UT3 Paul Sabatier), 2019. English. ⟨tel-02901461v2⟩



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