Aurelia POERIO : Élaboration par bio-impression 3D et caractérisation de biomatériaux naturels pour l'ingénierie tissulaire

Abstract :
3D bioprinting is a tissue engineering technology based on the combination of biomaterials, cells and bioactive molecules for the fabrication of tissue substitutes able to restore, replace and/or repair the damaged ones. Biomaterials act as a temporary extracellular matrix and promote the migration, proliferation and differentiation of cells. This ability is either due to biomaterial's intrinsic properties or to their modification through the inclusion of biochemical cues, such as growth factors. The objective of this thesis is to develop new biomaterials allowing 3D printing and new strategies allowing for their application in tissue engineering, using, in particular, the technology of 3D bioprinting. In order to do that, we firstly extracted chitin from an unusual source, cicadas sloughs, and transformed it into its derivative chitosan. These two polysaccharides were characterized from a physicochemical point of view. Furthermore, for the first time to our knowledge, we also characterized the raw material (i.e., cicada sloughs) and the intermediary products of the extraction process, which proved important to evaluate the stability of cicada sloughs as a source of chitin. Chitosan, a derivative of chitin, was then used to develop new biomaterial inks for extrusion 3D printing through its combination with two natural gums: guar gum and tamarind gum. These are polysaccharides derived from seed plants and widely used as thickening and gelling agents by the food industries. Their addition to chitosan improved its printability and, through a dual gelation mechanism, led to the fabrication of stable 3D constructs with improved mechanical properties. Subsequently, after reviewing the 3D bioprinting strategies used to control the release of growth factors from 3D printed and bioprinted constructs, PLGA microspheres were included into a 3D bioprinted skeletal muscle construct as neurotrophic factors delivery system in order to improve and accelerate the innervation of the developed scaffold.