Nanosize and Vitality:  TiO₂ Nanotube Diameter Directs Cell Fate

Abstract

We generated, on titanium surfaces, self-assembled layers of vertically oriented TiO2 nanotubes with defined diameters between 15 and 100 nm and show that adhesion, spreading, growth, and differentiation of mesenchymal stem cells are critically dependent on the tube diameter. A spacing less than 30 nm with a maximum at 15 nm provided an effective length scale for accelerated integrin clustering/focal contact formation and strongly enhances cellular activities compared to smooth TiO2 surfaces. Cell adhesion and spreading were severely impaired on nanotube layers with a tube diameter larger than 50 nm, resulting in dramatically reduced cellular activity and a high extent of programmed cell death. Thus, on a TiO2 nanotube surface, a lateral spacing geometry with openings of 30-50 nm represents a critical borderline for cell fate.

Flexible electrical recording from cells using nanowire transistor arrays

“…In addition, the typical calibrated voltages recorded in our measurements are similar to or greater than the largest values reported previously. The improvement in peak amplitude is consistent with the fact that the nanodevices protrude from the plane of substrate and hence can increase NW/cell interfacial coupling (17,(24)(25)(26)(27)(28) and with our previous studies of cultured neurons (14) and embryonic hearts (15). Recent studies using top-down fabricated NWs also reported millivolt-scale signals, although the cardiomyocytes in this case appeared morphologically undeveloped (e.g., Ϸ10-mdiameter spherical structures), and thus it is difficult to compare these results directly with our work and previous planar FET studies.…”

“…A unique feature of these studies compared with conventional planar devices measurements is that the nanodevices protrude from the plane of substrate, and hence can increase NW/cell interfacial coupling. Indeed, studies have shown that nanostructured interfaces can enhance cellular adhesion and activity (17,(24)(25)(26)(27)(28), and thus it is likely that NW and CNT devices have an intrinsic advantage for building interfaces to cells and tissue.…”

Another look at “Stem cell fate dictated solely by altered nanotube dimension”

“…Culturing human mesenchymal stem cells (MSCs) on a range of nanotubes with diameters between 30 and 100 nm, cell stretching and expression of osteogenic differentiation markers was highest on 100-nm nanotubes, whereas cell-adhesion rates increased with decreasing tube diameter, with a maximum at 30 nm. This finding is particularly striking in light of previous contrary reports showing that nanoscale-dependent differentiation of MSCs to osteoblasts followed in the opposite direction (2,3). In these studies, data were presented showing that not only adhesion, proliferation, and migration, but also osteogenic differentiation of rat bone marrow MSCs were highest on 15-nm nanotubes and decreased dramatically on 70-and 100-nm nanotubes.…”

The influence of surface roughness and high pressure torsion on the growth of anodic titania nanotubes on pure titanium

“…In addition, modifying the natural oxide layer of titanium, which provides remarkable surface properties, can address issues related to insufficient osseointegration [6] and undesired cell growth [7][8][9]. Titanium dioxide nanotubes (TNT) made by electrochemical anodization can modify the oxide layer, which can be utilized to positively affect cellular behaviours, such as migration [9], adhesion [10], proliferation [7,10,11] and differentiation [12,13]. By modifying the surfaces of SPD processed titanium with TNT layers, there is a possibility to simultaneously increase the bulk and surface properties, therefore further increasing the success rate of titanium implants.…”