Towards nanostructured bioactive surfaces to control cell behavior

Controlling cell fate on artificial surfaces is of great interest in fundamental research but also more concrete fields as tissue engineering or cancer research. Nowadays, features up to the nanoscale are designed directly on the surface to allow manipulation of cell behavior. An example could be the modification of surface topography by decorating the surface with nanopillars. Such structures are interesting since, for specific aspect-ratios, they do not affect cell viability and can influence cell behavior. Moreover, such structures can also give access to the cell cytosol meaning drug delivery of desired compounds directly inside the cell can be obtained. Since cytosol can be regarded as a reducing environment, redox responsive layers grafted on the nanopillars could be an option for drug delivery applications. Indeed, if a drug is anchored through disulfide bonds to the nanopillars, it could be released thanks to the glutathione/glutathione couple present in the cytosol. Moreover, disulfide bonds also show an excellent stability in extracellular medium meaning the sample could safely be exposed to the cell external environment without undesired drug release. The purpose of this work is to develop a bifunctionalized nanostructured surface. First, a flat surface is decorated with nanopillars. The top of the nanopillars is then coated with a polythiolactone copolymer on which a test component is grafted. The remaining surface is finally functionalized with a bioadhesive layer to promote cell adhesion on the surface and nanopillar endocytosis. The exposition of the top of the nanopillars to the reducing environment of the cytosol would result in the drug release inside the cell. In order to perform this bifunctionalization, a sacrificial layer is used. This layer would cover the whole surface except for the top of the nanopillars that can be functionalized with the polythiolactone copolymer. Dissolution of the sacrificial layer is then performed and the remaining surface is available for the second functionalization. Promising results were obtained for the different steps yielding to bifunctionalization of gold surfaces. Indeed, gold nanopillars of desired heigh and diameter were obtained on gold surfaces. Afterwards, the functionalization and bifunctionalization processes were studied and characterized. Polythiolactone copolymer grafting on flat and nanostructured gold surfaces was demonstrated. The spin-coating and etching of the sacrificial layer to reveal only the top of the nanopillars was also assessed and bifunctionalization could consecutively be performed. Finally, redox responsiveness of the copolymer layer when exposed to a reducing environment was assessed. Platinum was studied as an alternative to gold but was not retained because of the poor copolymer anchoring on the metal.Master [120] : ingénieur civil biomédical, Université catholique de Louvain, 201