Significantly accelerated osteoblast cell growth on aligned TiO<sub>2</sub> nanotubes

Oh, Seunghan; Daraio, Chiara; Chen, Li Han; Pisanic, Thomas R.; Fiñones, Rita; Jin, Sung‐Ho

doi:10.1002/jbm.a.30722

Cited by 451 publications

(392 citation statements)

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“…We also demonstrate that a guided osteogenic differentiation of hMSCs can be controllably manipulated by selective sizing of the nanotube dimensions. Because the TiO 2 nanotubes are excellent osseointegration biomaterials as evidenced by in vitro data (24), and our preliminary in vivo animal data indicating a strong new bone integration on the nanotube surface with reduced soft tissue trapping (data not shown), the nanotube surface can perform dual therapeutic functions of specifically guided differentiation and strong osseointegration for new bone formation. We forecast that these results can be a milestone for the further study of stem cell control and implant development, in terms of its application as a therapeutic platform as well.…”

Section: Discussionmentioning

confidence: 86%

“…We have described in previous studies (24) that the long-range structure of TiO 2 nanotubes is neither patterned nor highly ordered, but they do have a robust and discrete nanotube shape. Dalby et al (7) reported that MSC cultured on highly ordered poly(methylmethacrylate) (PMMA) nanopatterns showed negligible osteogenic differentiation, but randomized PMMA nanotopography demonstrated MSC osteoblastic morphologies after 21 days of incubation with cell growth media.…”

Section: Discussionmentioning

confidence: 93%

“…The protocol for preparation of TiO2 nanotubes by anodization process for cell culture is similar to what we used (5,24,25) and is described as follows. The nanotubes were formed on a Ti sheet (Alfa-Aesar; 0.25 mm thick, 99.5%) by using a mixture of 0.5 wt % hydrofluoric acid (EM Science; 48%) and acetic acid (Fisher; 98%, volumetric ratio ϭ 7:1) at 5, 10, 15, and 20 V for 30 min to obtain different diameter nanotubes.…”

Section: Methodsmentioning

confidence: 99%

“…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)(14)(15)(16), photocatalysis (17)(18)(19), photoelectrolysis (20), sensors (21,22), and biomaterials (23)(24)(25). The presence of a vertically aligned TiO 2 nanotube surface on Ti foils had a critical effect that improved the proliferation and mineralization of osteoblasts (24) and enhanced the mobility, vasodilation, and monolayer formation of endothelial cells (25) because of the unique nanotopographical features and high biocompatibility of the TiO 2 nanotube surface.…”

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confidence: 99%

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Stem cell fate dictated solely by altered nanotube dimension

Oh¹,

Brammer²,

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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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...

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Section: Discussionmentioning

confidence: 86%

Section: Discussionmentioning

confidence: 93%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Stem cell fate dictated solely by altered nanotube dimension

Oh¹,

Brammer²,

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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“…Third, there are differences in the nature of the TiO 2 nanotubes used. The nanotubes used by Park et al were as-anodized amorphous phase, whereas those used in our study were heat treated and crystallized, anatase phase; we have previously demonstrated that crystallized TiO 2 nanotubes are superior in osteoblast cell adhesion and growth (5,6) and that the anatase phase plays an important role in proliferation and cell morphology. Furthermore, Park et al's (2, 3) amorphous nanotube samples can exhibit 5% fluorine at the sample surface (3), whereas our sample (4) surface was high-temperature annealed at 500°C to thermally decompose and remove most of the fluorine (XPS showing only 0.4%).…”

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confidence: 87%

Reply to von der Mark et al.: Looking further into the effects of nanotube dimension on stem cell fate

Oh¹,

Brammer²,

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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In their Letter to the Editor, von der Mark et al.(1) stated that they found adhesion, proliferation, migration, and osteogenic differentiation of rat bone marrow mesenchymal stem cells (MSCs) to be highest on 15-nm TiO 2 nanotubes and to be dramatically decreased on 70-and 100-nm nanotubes (2, 3). These findings are contrary to our results with human mesenchymal stem cells on a range of nanotubes with 30-to 100-nm diameter, where cell stretching and expression of osteogenic differentiation markers was highest on 100 nm nanotubes (4). Park et al. (2,3) illustrated that the optimum length scale for cell vitality and differentiation was shown to be the small-diameter nanotubes (Ϸ15 nm), in contrast to the large diameter of 100nm in our study (4). The opposite results found in the refs. 2 and 3 are interesting, and we agree that further discussion and experimentation are needed for their resolution.First, we would like to point out that the Park et al. (2, 3) studies and our study (4) used MSCs from different species and origins: rat bone marrow stem cells (2, 3) vs. human mesenchymal stem cells (4). Second, Park et al. (2, 3) used osteogenic induction media, whereas we only used regular cell growth media without any osteogenic inducing media, osteogenic supplements, or growth factors. Third, there are differences in the nature of the TiO 2 nanotubes used. The nanotubes used by Park et al. were as-anodized amorphous phase, whereas those used in our study were heat treated and crystallized, anatase phase; we have previously demonstrated that crystallized TiO 2 nanotubes are superior in osteoblast cell adhesion and growth (5, 6) and that the anatase phase plays an important role in proliferation and cell morphology. Furthermore, Park et al.'s (2, 3) amorphous nanotube samples can exhibit 5% fluorine at the sample surface (3), whereas our sample (4) surface was high-temperature annealed at 500°C to thermally decompose and remove most of the fluorine (XPS showing only 0.4%). It has been demonstrated that fluorine has various degrees of effects on implant surfaces (7-9), and different nanotube pore openings may lead to different degrees of phosphoric or hydrofluoric acid residues which may be beneficial or induce toxicity to cells.The discussion above points to several key differences in the experimental conditions used in the Park studies (2, 3) and our study (4). Although these differences make it difficult to directly compare the results of these studies, the findings of opposite effects of nanotube diameter on osteogenesis of MSCs showed the striking variabilities and opportunities to choose different substrate topography for the purpose of influencing and controlling stem cell fate and motivate more systematic studies on the effects of TiO 2 nanotube geometry, materials, processing parameters, surface chemistry, crystal structure, and other differentiation approaches on behaviors of different types of stem cells. This will help us achieve the ultimate goal of establishing the optimum microenvironment, including tha...

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