Unconventional Multi-Scale Patterning of Titanium Dioxide: A New Tool for the Investigation of Cell-Topography Interactions

Titanium dioxide (TiO2) is a biocompatible material with important applications in the field of regenerative medicine. Here we show that a multi‐scale hierarchical architecture of TiO2, realized with sub‐micrometer polystyrene beads as templating agent patterned by “micromolding in capillaries” (MIMICs), is a viable functional tool for the systematic investigation of cell behavior with respect to a complex topographic texture of the substrate. TiO2 stripes of different width and interconnected porosity whose size ranges from a few hundred to a few tens nanometer, are obtained after thermal treatment of the precursors with concurrent removal of the templating agent. The adhesion and proliferation of two human secondary neural cell lines, i.e., 1321N1 astrocytoma and SH‐SY5Y neuroblastoma, on the patterns is statistically assessed with respect to the TiO2 stripe width and porosity. Our results show that cells have a strong preference for TiO2 patterns with respect to glass, the proliferation rate is not affected by cell porosity whereas adhesion is although ligthly, whereas the response of cell density to stripe width is very different in astocytoma cells with respect to neuroblastoma cells. A multi‐scale architecture of titanium dioxide (TiO2) is realized through the “micromolding in capillaries” technique, employing sub‐micrometer polystyrene beads as templating agent. The viability of TiO2 pattern as a tool for the systematic investigation of cell behavior with respect to a complex topography of the substrate is evaluated, by analyzing the growth of two human neural cell lines with respect to the width and porosity of the patterned stripes.