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...

Engineered magnetic nanoparticles (MNPs) represent a cutting-edge tool in medicine because they can be simultaneously functionalized and guided by a magnetic field. Use of MNPs has advanced magnetic resonance imaging (MRI), guided drug and gene delivery, magnetic hyperthermia cancer therapy, tissue engineering, cell tracking and bioseparation. Integrative therapeutic and diagnostic (i.e., theragnostic) applications have emerged with MNP use, such as MRI-guided cell replacement therapy or MRI-based imaging of cancer-specific gene delivery. However, mounting evidence suggests that certain properties of nanoparticles (e.g., enhanced reactive area, ability to cross cell and tissue barriers, resistance to biodegradation) amplify their cytotoxic potential relative to molecular or bulk counterparts. Oxidative stress, a 3-tier paradigm of nanotoxicity, manifests in activation of reactive oxygen species (ROS) (tier I), followed by a pro-inflammatory response (tier II) and DNA damage leading to cellular apoptosis and mutagenesis (tier III). In vivo administered MNPs are quickly challenged by macrophages of the reticuloendothelial system (RES), resulting in not only neutralization of potential MNP toxicity but also reduced circulation time necessary for MNP efficacy. We discuss the role of MNP size, composition and surface chemistry in their intracellular uptake, biodistribution, macrophage recognition and cytotoxicity, and review current studies on MNP toxicity, caveats of nanotoxicity assessments and engineering strategies to optimize MNPs for biomedical use.

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Vertically aligned yet laterally spaced nanoscale TiO2 nanotubes have been grown on Ti by anodization, and the growth of MC3T3-E1 osteoblast cells on such nanotubes has been investigated. The adhesion/propagation of the osteoblast is substantially improved by the topography of the TiO2 nanotubes with the filopodia of growing cells actually going into the nanotube pores, producing an interlocked cell structure. The presence of the nanotube structure induced a significant acceleration in the growth rate of osteoblast cells by as much as approximately 300-400%.