Dynamic bioactive surfaces for cells using cucurbiturils

Creating biomimetic materials with tailored cellular responses upon engaging with cells is a core challenge in biomaterials, medical devices and tissue regenerative medicine. The cell machinery is enormously complex with precisely regulated cues present in space and time. Fine tuning the spacing between artificial bioactive cues on surfaces has shown to be a crucial design criterium for cells that interact with materials. By adding dynamicity and control over temporal positioning of ligands, stimuli-responsive surfaces of biomaterials and devices open up new opportunities to steer cellular fate and study cellular mechanisms. Supramolecular host-guest interactions are in itself dynamic in nature due to non-covalent interactions between molecules while in addition they allow for the incorporation of guests, whose presence can be changed using external stimuli. This makes them highly attractive for the exploration of cell-interactive surfaces for biological applications. In this thesis strategies to anchor bioactive ligands employing supramolecular hostguest chemistry are presented and discussed in the context of engaging these surfaces with cells. To ensure specific interaction of the bioactive ligands with cells, different surfaces anchoring strategies have been explored in the first part of the thesis. Studying the specific interaction with cells and subsequent triggered cell detachment using electrochemistry is a central part of this thesis and special attention has been given to the development of a suitable platform for performing in vitro cell studies. In the final part of the thesis it becomes evident that when bioactive ligands are noncovalently anchored onto surface the observed cell adhesion temporal dynamics in terms of spreading, shape and cell polarization is distinctively different from surface bearing bioactive ligands covalently. More surprisingly, the cellular response more closely resembles that of cells that are cultured on surfaces with native extracellular matrix protein fibronectin and this finding encourages further research to elicit the underlying mechanisms of this response. In the epilogue a few examples are given to highlight future work on how supramolecular chemistry could be further applied in advancing biomedical devices.