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

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.