Synergistic Control of Mesenchymal Stem Cell Differentiation by Nanoscale Surface Geometry and Immobilized Growth Factors on TiO₂ Nanotubes

Abstract

The aim of this study is to elucidate whether combined environmental signals provided by nanoscale topography and by growth factors control cell behavior of mesenchymal stem cells (MSCs) in a synergistic or simply additive manner. Chondrogenic and osteogenic differentiation of MSCs is studied on vertically aligned TiO(2) nanotubes of size 15 and 100 nm with and without immobilized bone morphogenetic protein-2 (BMP-2). Although BMP-2 coating stimulates both chondrogenic and osteogenic differentiation of MSCs, the response strongly depends on the surface nanoscale geometry of the BMP-2-coated nanotubes. Chondrogenic differentiation is strongly supported on 100 nm BMP-2-coated nanotubes, but not on 15 nm nanotubes, which induce spreading and de-differentiation of chondrocytes. A similar response is observed with primary chondrocytes, which maintain their chondrogenic phenotype on BMP-2-coated 100 nm nanotubes, but de-differentiate on 15 nm nanotubes. In contrast, osteogenic differentiation is greatly enhanced on 15 nm but not on 100 nm BMP-2-coated nanotubes as shown previously. Furthermore, covalent immobilization of BMP-2 rescues MSCs from apoptosis occurring on uncoated 100 nm TiO(2) nanotube surfaces. Thus, combined signals provided by BMP-2 immobilized to a defined lateral nanoscale spacing geometry seem to contain environmental cues that are able to modulate a lineage-specific decision of MSC differentiation and cell survival in a synergistic manner.

One-Dimensional Titanium Dioxide Nanomaterials: Nanotubes

“…Immobilization of BMP-2 can be performed by polydopamine, 949 by an amino-functional organisilane (APTES), 956 or by carbonyldiimidazol 948,950 . BMP-2 functionalized nanotubes via polydopamine proved beneficial for cell proliferation and differentiation (higher osteocalcin and osteopontin levels), 949 while the uncoated nanotubes showed the clear size effects of small diameter nanotubes.…”

Optimizing stem cell functions and antibacterial properties of TiO2 nanotubes incorporated with ZnO nanoparticles: experiments and modeling

“…5 To further improve the osteogenic properties of TiO 2 bone growth factors and bone morphogenetic proteins) can be embedded into TNTs. [6][7][8] However, growth factors and proteins are easily degraded at high temperatures used during the sterilization processes. 9 Similarly, the release of bioactive proteins from TNTs may not be stable enough in vivo and may result in large initial release profiles unhealthy for new bone formation.…”

Nanoscale TiO2 nanotubes govern the biological behavior of human glioma and osteosarcoma cells

“…4,5 Simultaneously, the transfer of internal activities relies greatly on external materials. 6 This complicated process is commonly referred to as bidirectional signal transduction, in which cellular adhesion and material surface properties correlate intimately. In tissue engineering, the surface properties of biological materials usually impose crucial impacts on cell culture, 7 healing of wounds, 8 and tissue restoration and reconstruction.…”