Abstract :
[en] Over the last decades, porous matrices, called scaffolds, have increasingly gained in importance for bone regeneration. These matrices have been tailored to support and control the spatial organization of stem cells. Even though various materials have been proposed for their conception, their in vivo assessments have highlighted their lack of bioactivity and integration. In this context, this thesis focused on the development of biodegradable scaffolds with surface properties specifically designed to promote bone regeneration by a sustained local delivery of growth factors.
The first part was devoted to the optimization of calcium phosphate ceramics in order to obtain inorganic matrices with well-defined composition and textural properties in contrast to commercially available materials. In this context, two methods of ceramic preparation were compared: wet precipitation method and sol-gel process. The resulting powders were processed into disks via a press-molding process and into tridimensional matrices via a sponge replication technique. Their resistance to post-treatments, i.e. calcination and sterilization, was also assessed.
The second, third, and fourth parts of this work focused on the functionalization and the texturing of silica, selected as material for the surface modification of calcium phosphate ceramics, to promote the local sustained delivery of growth factors. The textural and chemical properties of silica were tuned to control the encapsulation and the release of a model protein of these growth factors. More specifically, three different strategies were investigated to adjust the protein loading and its release kinetics: (i) the protein encapsulation method, (ii) the addition of functionalized organosilanes, and (iii) the structuration of the silica texture. In the second part, the influence of the encapsulation method on the release kinetics and activity of protein was examined via the impregnation of silica gels with a protein solution and the direct incorporation of the protein during the synthesis of the silica gel. The results showed that a continuous protein release over 80 days could be obtained.
The third part focused on the modification of the silica surface composition and textural properties via the use of different functionalized organosilanes (i.e. containing amine, ethylene diamine, or phenyl groups) and silica precursors (i.e. containing methoxy or ethoxy groups) in order to modulate the release rate of the protein. The results highlighted the preponderant role of the matrix hydrophilicity on the protein encapsulation and release compared to its surface charge.
The fourth part studied the influence of the structuration of mesoporous silica on the protein encapsulation and release. SBA-15 type silica with large mesopores were synthesized using different silica precursors (i.e. containing or not phenyl groups) to offer a greater control of the material composition and textural properties. The results demonstrated that the structuration of silica allowed a regulation of the protein release over a longer period than the absence of structure.
In the last part of this work, the surface modification of calcium phosphate scaffolds was investigated through the deposition of a composite made of silica particles dispersed in agarose. Specifically, this part consisted in an exploratory study focusing on the production and the characterization of the silica/agarose composite. The promising results of this part highlighted that agarose was not a barrier to the protein diffusion, suggesting that agarose could be adopted as a matrix to disperse silica for drug delivery applications.
