Existence of a typical threshold in the response of human mesenchymal stem cells to a peak and valley topography

Our objective in this study was to determine whether a threshold in sensitivity of human mesenchymal stem cells (hMSC) to isotropic roughness exists. Using electrical discharge machining a very wide range of roughnesses (1.2 μm < Ra < 21 μm) with a perfectly isotropic, fractal and self-affine topography can be produced on titanium, with a range of roughness overlapping the hMSC length dimensions. The curve of the number of adherent hMSC after 2 days culture as a function of roughness showed a U-shape with a minimum number of attached cells for a roughness amplitude Ra = 4.5 μm and a distance between surface features (width of peaks and valleys) Sm = 110 μm. The maximum cell number was observed at the lowest and highest roughnesses. Due to this very wide range of roughness it was possible to demonstrate that the response of hMSC to roughness varies with the dimensions of the surface features relative to the cell size. Above or below their own size hMSC essentially adhere to the nano and submicron features. When the surface displays features about the same size as hMSC the curvature of these surface features will decrease the number of attached cells by a factor of two. A modelling approach is proposed to help the interpretation of these results. It is hypothesized that this minimal adhesion is a consequence of an unfavourable stress imposed on the cell cytoskeleton.