Influence of nanopatterend titanium surfaces on the osteogenic differentiation of human mesenchymal stem cells in combination with chemical and biological surface modifications (NanoTune)

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The influence of anisotropic, ordered surface topographies at the low nanometer level on the behavior of human mesenchymal stem cells (hMSC) is thus far insufficiently investigated and poorly understood. Yet topographies with vertical dimensions in the sub-10 nm range and lateral dimensions of the order few 10 nm exhibit high potential to significantly influence cellular attachment and osteogenic commitment, especially in combination with tailored chemical and biochemical surface modifications. This study therefore aims at investigating the hypothesis that such nanostructures on titanium substrates can significantly influence protein adsorption as well as hMSC adhesion, migration, and osteogenic differentiation, both by themselves and amplified with chemical and biological surface modifications. Low-energy ion bombardment will be used to generate ordered wave-like ripple patterns with lateral periodicities of few ten nanometers and heights in the range from < 1 nm to 5 nm. Subsequently, tailored surface chemistry will be generated by silanization, and crosslinking will be used to specifically couple two proteins, vitronectin and fibronectin, which play major roles in cell adhesion, migration, and differentiation. The unmodified as well as the chemically diversified surfaces will furthermore be investigated for their ability to unspecifically adsorb proteins, using QCM-D, AFM, and PM-IRRAS among others, as well as immunocytochemistry assays. Established adhesion, migration and differentiation assays will subsequently be used to characterize the surface induced cellular responses of the seeded hMSC. The topographical, chemical, and biochemical parameters will then be systematically varied to reveal the respective influences of the individual surface modifications on the cells. For this, extensive in-vitro analyses of the morphology, cellular composition and reorganization, proliferation, and differentiation behavior of the hMSC will be conducted. The data gathered within this study, regarding stem cell response to substrate topographies at the low-nanometer level, will thus be helpful to improve future design and availability of e.g. orthopaedic and dental implants.