Anodic titanium dioxide (TiO2) nanostructures, i.e., obtained by electrochemical anodization, have excellent control over the nanoscale morphology and have been extensively investigated in biomedical applications owing to their sub-100 nm nanoscale topography range and beneficial effects on biocompatibility and cell interactions. Herein, we obtain TiO2 nanopores (NPs) and nanotubes (NTs) with similar morphologies, namely, 15 nm diameter and 500 nm length, and investigate their characteristics and impact on stem cell adhesion. We show that the transition of TiO2 NPs to NTs occurs via a pore/wall splitting mechanism and the removal of the fluoride-rich layer. Furthermore, in contrast to the case of NPs, we observe increased cell adhesion and proliferation on nanotubes. The enhanced mesenchymal stem cell adhesion/proliferation seems to be related to a 3-fold increase in activated integrin clustering, as confirmed by immunogold labeling with β1 integrin antibody on the nanostructured layers. Moreover, computations of the electric field and surface charge density show increased values at the inner and outer sharp edges of the top surfaces of the NTs, which in turn can influence cell adhesion by increasing the bridging interactions mediated by proteins and molecules in the environment. Collectively, our results indicate that the nanoscale surface architecture of the lateral spacing topography can greatly influence stem cell adhesion on substrates for biomedical applications.

Department of Materials Science WW4 LKO Friedrich Alexander University of Erlangen Nürnberg 91054 Erlangen Germany

Division of Molecular Pediatrics Department of Pediatrics University Hospital Erlangen 91054 Erlangen Germany

Laboratory of Clinical Biophysics Faculty of Medicine University of Ljubljana Vrazov Trg 2 Ljubljana 1000 Slovenia

Laboratory of Physics Faculty of Electrical Engineering University of Ljubljana Tržaška 25 Ljubljana SI 1000 Slovenia

Regional Centre of Advanced Technologies and Materials Czech Advanced Technology and Research Institute Palacky University Olomouc 779 00 Czech Republic

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