Two important goals in stem cell research are to control the cell proliferation without differentiation and to direct the differentiation into a specific cell lineage when desired. Here, we demonstrate such paths by controlling only the nanotopography of culture substrates. Altering the dimensions of nanotubular-shaped titanium oxide surface structures independently allowed either augmented human mesenchymal stem cell (hMSC) adhesion or a specific differentiation of hMSCs into osteoblasts by using only the geometric cues, absent of osteogenic inducing media. hMSC behavior in response to defined nanotube sizes revealed a very dramatic change in hMSC behavior in a relatively narrow range of nanotube dimensions. Small (Ϸ30-nm diameter) nanotubes promoted adhesion without noticeable differentiation, whereas larger (Ϸ70-to 100-nm diameter) nanotubes elicited a dramatic stem cell elongation (Ϸ10-fold increased), which induced cytoskeletal stress and selective differentiation into osteoblast-like cells, offering a promising nanotechnology-based route for unique orthopedics-related hMSC treatments.differentiation ͉ mesenchymal ͉ nanotopography ͉ osteogenesis ͉ proliferation N anostructures are of particular interest because they have the advantageous feature of a high surface-to-volume ratio, and they elicit a higher degree of biological plasticity compared with conventional micro-or macrostructures. In the field of biomaterial development and in vivo implant technology, the nanoscale structure and morphologenic factor of the surface have played a critical role in accelerating the rate of cell proliferation and enhancing tissue acceptance with a reduced immune response (1, 2). In terms of in vitro cell biology, there has also been much attention placed on cellular responses to their structural surroundings (3). In fact, it has been observed that macro-, micro-and nano-sized topographical factors stimulate behavioral changes in both cells and tissues. Recent studies related to the effect of nanotopography on cellular behavior indicated that osteoblast adhesion and functionality was enhanced by 30% when cultured on a nanograined Al 2 O 3 and TiO 2 substrate (4-6) compared with those cultured on a micrograined surface, and nanostructures such as TiO 2 nanotubes with Ͻ100-nm spacing showed superior characteristics in bone mineral synthesis (5). However, most of the previous studies on nanostructures and cell responses have mainly used oriented, patterned, or semiordered polymer arrays (7-9) and alumina/ polymer hybrid patterned arrays (10).The material and mechanical characteristics of titanium (Ti) metal, which has a thin native oxide layer of TiO 2 , make it an ideal orthopedic material that bonds directly to the adjacent bone surface (11,12). Fabrication of the nanostructured titanium dioxide (TiO 2 ) nanotube arrays has been a primary subject of investigation lately because of the wide range of TiO 2 applications in the fields of solar cells (13-16), photocatalysis (17-19), photoelectrolysis (20), sensors (21,22), and b...
Implant topography is critical to the clinical success of bone-anchored implants, yet little is known how nano-modified implant topography affects osseointegration. We investigate the in vivo bone bonding of two titanium implant surfaces: titanium dioxide (TiO(2)) nanotubes and TiO(2) gritblasted surfaces. In previous in vitro studies, the topography of the TiO(2) nanotubes improved osteoblast proliferation and adhesion compared with gritblasted titanium surfaces. After four weeks of implantation in rabbit tibias, pull-out testing indicated that TiO(2) nanotubes significantly improved bone bonding strength by as much as nine-fold compared with TiO(2) gritblasted surfaces. Histological analysis confirmed greater bone-implant contact area, new bone formation, and calcium and phosphorus levels on the nanotube surfaces. It is anticipated that further studies will contribute to a better understanding of the effect of implant nanotopography on in vivo bone formation and bonding strength.
The in vitro endothelial response of primary bovine aortic endothelial cells (BAECs) was investigated on a flat Ti surface vs a nanostructured TiO2 nanotube surface. The nanotopography provided nanoscale cues that facilitated cellular probing, cell sensing, and especially cell migration, where more organized actin cytoskeletal filaments formed lamellipodia and locomotive morphologies. Motile cell protrusions were able to probe down into the nanotube pores for contact stimulation, and focal adhesions were formed and disassembled readily for enhanced advancement of cellular fronts, which was not observed on a flat substrate of titanium. NOx and endothelin-1 functional assays confirmed that the nanotubes also up-regulated an antithrombic cellular state for maintaining vascular tone. The enhanced endothelial response to TiO2 nanotubes is significant for a potential modification of vascular stent surfaces in order to increase the rate and reliability of endothelialization and endothelial cell migration onto the stent for repairing arterial injury after activation.
Nanocapsules containing intentionally trapped magnetic nanoparticles and defined anticancer drugs have been prepared to provide a powerful magnetic vector under moderate gradient magnetic fields. These nanocapsules can penetrate into the interior of tumors and allow a controlled on-off switchable release of the drug cargo via remote RF field. This smart drug delivery system is compact as all the components can be self-contained in 80-150 nm capsules. In vitro as well as in vivo results indicate that these nanocapsules can be enriched near the mouse breast tumor and are effective in reducing tumor cell growth.
Loading or filling nanostructures with antibiotics can be one of the relevant approaches for obtaining a controlled drug release rate. Vertically aligned silicon nanowire (SiNW) arrays with 10-40 nm diameter wires having 1-3 microm in length obtained by the electroless etching (EE) technique are used in this study as novel nanostructures for mediating drug delivery. Here we report controlled antibiotic activity and sustained bioavailability from SiNW arrays and also show microstructural manipulations for a tunable release rate. As well, we have demonstrated biodegradability of SiNWs in phosphate buffer saline (PBS) solution. Strikingly suppressed cell and protein adhesion was observed on our SiNW surface, which indicates a reduced probability for biofouling and drug release impediments. Such antibiotic release from the nanowire-structured surface can provide more reliable antibiotic protection at a targeted implantation or biosensor site.
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