Conception de biomatériaux hybrides poreux adaptés à l'encapsulation de cellules animales pour la thérapie cellulaire

Among the diseases induced by protein or hormone deficiencies, type 1 diabetes mellitus is becoming increasingly widespread and makes life very difficult for people who are affected. It is characterized by the destruction of the insulin secreting β-cells by the immune system. The most commonly used treatment is the insulinotherapy which implies a drastic diet and much attention from the patient who is all the time put at risk of hyper- or hypoglycemia. A first alternative is the transplantation of pancreas or islets of Langerhans but the low number of donor and the necessity to follow an immunosuppressive medication to prevent the graft rejection are serious drawbacks. A promising solution for the treatment of this type of disease is the encapsulation of xenogeneic cells within a biocompatible, robust and semi-permeable material which will protect them against immune system or mechanical stress This thesis highlights the possibility of using mineralized TiO2 microcapsules synthesized under mild conditions as “artificial organ”. This original material has been developed by overcoming constraints induced by the use of alkoxy precursors in the inorganic materials preparation by sol-gel process such as the toxicity of some additives and of the by-products of reaction or the matrix contraction over time. This artificial organ is obtained by using alginate capsules entrapping animal cells as a template for the deposition of a TiO2 layer. Various techniques underscored the biocompatibility, the high mechanical strength and the ideal porosity of the microcapsules while showing the prolongation of the viability and of the activity of the encapsulated HepG2 model cells. In vivo experiments realized on rats highlighted the biocompatibility of the microcapsules towards a living host organism and the efficient encapsulated cells immune-isolation. Finally, the encapsulation of insulin secreting rat insulinoma-derived INS-1E cells showed that these cells retained their in vitro responsive property to glucose for insulin secretion and that this hormone diffused well outside of the microcapsules. This work allowed designing and developing a robust, biocompatible and porous biomaterial as an artificial organ suitable for the cell therapy.