Nanostructuration of silica particles and design of composite biomaterials

This work describes the design of tunable biomaterials for tissue engineering. The composite approach provides numerous advantages to enhance cell adhesion and control bioactivity by complying both with structural and functional requirements. The host matrix, made from a natural macromolecule (collagen), or from synthetic supramolecular polymers (peptide amphiphiles), provides a suitable structural environment to the cells and can also display intrinsic biochemical cues to influence cell behavior. Functionalized silica nanoparticles can be added to be used as platforms either to further tune the architecture of the scaffold or display additional bioactive ligands. The combination of peptide amphiphiles with such nanoparticles led to composite biomaterials with high modularity allowing to compare different displays of one bioactive epitope and the simultaneous grafting of two epitopes known to work in a distance-dependent manner. The next step was to achieve the control of the spatial organization of several functions on the surface of a single nanoparticle. We have developed an original and challenging strategy based on the synthesis of self-assembling alkoxysilane precursors that could form pre-organized domains to be transferred at the silica nanoparticle surface to create patches. A large library of mono- and bifunctional particles were prepared that were incorporated in collagen-based threads evaluated in a model of peripheral nerve regeneration. Finally, we have elaborated thin porous scaffolds by electrospinning collagen in non-denaturing conditions that should allow to improve the cells access to the functional nanoparticles.