Nanostructured bioactive surfaces to control cell behaviour

With the emergence of nanotechnologies, smart surfaces and biointerfaces are being developed increasingly fast. These could potentially allow a better control over cell processes with an improved manipulation of cell fate. Moreover, smart surfaces are promising for the development of innovative drug delivery systems. Several researches have already proven that nanopillars can provide a direct access to the cell, with the delivery of DNA and other compounds of interest inside the cell medium. On the other hand, it has been proven that a controlled release of drugs can be achieved by using redox-responsive surfaces. A particularly interesting type of redox-responsiveness is based on the reversible formation of a disulfide bond. Indeed, disulfide bondings are characterised by an excellent stability in extracellular medium whereas they are rapidly degraded if exposed to the intracellular medium. This is because it is a reductive environment maintained by the glutathione/glutathione disulfide couple. The project of which this thesis is a part, intends to investigate the combination of nanopillars with a redox-responsive coating for drug delivery applications. Therefore gold nanopillars need to be functionalised by grafting a thiol containing copolymer. But only a fraction of the thiol functions are grafted to the gold surface, the remaining part is used to attach thiolated compounds. When the nanopillars penetrate inside the cell, the copolymer is submitted to its reductive environment triggering the release of the attached thiolated compounds inside the cell. In this study, we developed and optimised a strategy to selectively functionalise the top of the gold nanopillars by copolymer grafting. This could open the way to the fabrication of chemically and topographically patterned surfaces. Our strategy is based on the deposition of a sacrificial, protecting layer onto the gold nanostructured surfaces. This layer is subsequently partially etched in order to only expose the top of the gold nanopillars. Thereafter the copolymer is grafted on the exposed gold surface (tops of the nanopillars only) and the remaining sacrificial layer is dissolved. Characterisation results of the obtained selectively functionalised gold surfaces proved the efficiency of our strategy. Copolymer grafting was effectively observed and only low gold surface coverage was established. Furthermore, we also investigated complete functionalisation (i.e. funtionalisation of the whole available gold surface) of nanostructured gold surfaces by copolymer grafting. Results indicate that grafting on nanostructured surfaces is less efficient than on flat controls. The reason behind this is not clearly understood. Nevertheless the surface topography and the geometry of the nanopillar seem to play an important role. Finally, we evaluated the redox-responsiveness of a completely functionalised nanostructured gold surface by copolymer grafting. We compared the obtained results with flat controls. Results show that the redox-responsive property is still present although less pronounced than on flat controls.