TiO2 nanotubes as drug nanoreservoirs for the regulation of mobility and differentiation of mesenchymal stem cells

The extracellular microenvironment plays a key role in the regulation of cellular behavior. To mimic the natural extracellular microenvironment, TiO2 nanotube (TNT) arrays as drug nanoreservoirs for loading of bone morphogenetic protein 2 (BMP2) were constructed on titanium substrates and then covered with multilayered coatings of gelatin/chitosan (Gel/Chi) for controlled drug release. The multilayered coatings were constructed via a spin-assisted layer-by-layer assembly technique. The successful fabrication of this system was monitored by field emission scanning electron microscopy, atomic force microscopy, X-ray photoelectron spectroscopy and contact angle measurements. Multilayered coating with Gel/Chi retained the drug bioactivity and release properties, which were revealed by superoxide dismutase activity measurement. In addition, cytoskeleton observation and wound healing assay confirmed that BMP2-loaded and multilayer-coated TNT arrays were able to stimulate motogenic responses of mesenchymal stem cells (MSCs). More importantly, the system demonstrated that it was capable of promoting the osteoblastic differentiation of MSCs. This study may have potential impact on the development of bone implants for enhanced bone osseointegration.