Christine J. Frandsen

TiO2 nanotubes for bone regeneration

Nanostructured materials are believed to play a fundamental role in orthopedic research because bone itself has a structural hierarchy at the first level in the nanometer regime. Here, we report on titanium oxide (TiO(2)) surface nanostructures utilized for orthopedic implant considerations. Specifically, the effects of TiO(2) nanotube surfaces for bone regeneration will be discussed. This unique 3D tube shaped nanostructure created by electrochemical anodization has profound effects on osteogenic cells and is stimulating new avenues for orthopedic material surface designs. There is a growing body of data elucidating the benefits of using TiO(2) nanotubes for enhanced orthopedic implant surfaces. The current trends discussed within foreshadow the great potential of TiO(2) nanotubes for clinical use.

Hydrophobic nanopillars initiate mesenchymal stem cell aggregation and osteo-differentiation

Surface engineering approaches that alter the physical topography of a substrate could be used as an effective tool and as an alternative to biochemical means of directing stem cell interactions and their subsequent differentiation. In this paper we compare hydrophobic micro- vs. nanopillar type fabrication techniques for probing mesenchymal stem cell (MSC) interaction with the surface physical environment. The roles played by the topography of the nanopillar in particular influenced MSC growth and allowed for regulatory control of the stem cell fate. The nanopillar induced large 3-D cell aggregates to form on the surface which had up-regulated osteogenic specific matrix components. The ability to control MSC differentiation, using only the topographical factors, has a profound effect on both MSC biology and tissue engineering. This study aims to highlight the importance of the physical material carrier in stem cell based tissue engineering schemes.

Dye-Sensitized Solar Cell Constructed with Titanium Mesh and 3-D Array of TiO2 Nanotubes†

We have designed and constructed dye sensitized solar cells based on new, 3-D configurations of TiO(2) nanotubes. The overall efficiency of our best cells is 5.0% under standard air mass 1.5 global (AM 1.5 G) solar conditions, and the incident photon-to-current efficiency exceeds 60% over a broad part of the visible spectrum. Unlike prior nanotube-based cells where tubes are grown vertically in a 2-D array, the anodes of the present cells consist of tubes that extend radially in a 3-D array from a grid of fine titanium wires. The nanotubes are tens of micrometers in length, and the radial nature of the anode allows the photon absorption path length to exceed the electron transport distance (nanotube length). The cells are front-illuminated and do not require a transparent conductive oxide substrate at either the anode or cathode. The use of 3-D configured nanotubes and low-resistance titanium metal substrates are expected to enhance the performance and simplify the construction of large area dye-sensitized solar cells.

Comparative cell behavior on carbon-coated TiO2 nanotube surfaces for osteoblasts vs. osteo-progenitor cells.

Surface engineering approaches that alter the topological chemistry of a substrate could be used as an effective tool for directing cell interactions and their subsequent function. It is well known that the physical environment of nanotopography has positive effects on cell behavior, yet direct comparisons of nanotopographic surface chemistry have not been fully explored. Here we compare TiO(2) nanotubes with carbon-coated TiO(2) nanotubes, probing osteogenic cell behavior, including osteoblast (bone cells) and mesenchymal stem cell (MSC) (osteo-progenitor cells) interactions with the different surface chemistries (TiO(2) vs. carbon). The roles played by the material surface chemistry of the nanotubes did not have an effect on the adhesion, growth or morphology, but had a major influence on the alkaline phosphatase (ALP) activity of osteoblast cells, with the original TiO(2) chemistry having higher ALP levels. In addition, the different chemistries caused different levels of osteogenic differentiation in MSCs; however, it was the carbon-coated TiO(2) nanotubes that had the greater advantage, with higher levels of osteo-differentiation. It was observed in this study that: (a) chemistry plays a role in cell functionality, such as ALP activity and osteogenic protein gene expression (PCR); (b) different cell types may have different chemical preferences for optimal function. The ability to optimize cell behavior using surface chemistry factors has a profound effect on both orthopedic and tissue engineering in general. This study aims to highlight the importance of the chemistry of the carrier material in osteogenic tissue engineering schemes.

Tantalum coating on TiO2 nanotubes induces superior rate of matrix mineralization and osteofunctionality in human osteoblasts

Nanostructured surface geometries have been the focus of a multitude of recent biomaterial research, and exciting findings have been published. However, only a few publications have directly compared nanostructures of various surface chemistries. The work herein directly compares the response of human osteoblast cells to surfaces of identical nanotube geometries with two well-known orthopedic biomaterials: titanium oxide (TiO2) and tantalum (Ta). The results reveal that the Ta surface chemistry on the nanotube architecture enhances alkaline phosphatase activity, and promotes a ~30% faster rate of matrix mineralization and bone-nodule formation when compared to results on bare TiO2 nanotubes. This study implies that unique combinations of surface chemistry and nanostructure may influence cell behavior due to distinctive physico-chemical properties. These findings are of paramount importance to the orthopedics field for understanding cell behavior in response to subtle alterations in nanostructure and surface chemistry, and will enable further insight into the complex manipulation of biomaterial surfaces. With increased focus in the field of orthopedic materials research on nanostructured surfaces, this study emphasizes the need for careful and systematic review of variations in surface chemistry in concurrence with nanotopographical changes.

Preparation of near micrometer-sized TiO2 nanotube arrays by high voltage anodization.

Highly ordered TiO2 nanotube arrays with large diameter of 680-750 nm have been prepared by high voltage anodization in an electrolyte containing ethylene glycol at room temperature. To effectively suppress dielectric breakdown due to high voltage, pre-anodized TiO2 film was formed prior to the main anodizing process. Vertically aligned, large sized TiO2 nanotubes with double-wall structure have been demonstrated by SEM in detail under various anodizing voltages up to 225 V. The interface between the inner and outer walls in the double-wall configuration is porous. Surface topography of the large diameter TiO2 nanotube array is substantially improved and effective control of the growth of large diameter TiO2 nanotube array is achieved. Interestingly, the hemispherical barrier layer located at the bottom of TiO2 nanotubes formed in this work has crinkles analogous to the morphology of the brain cortex. These structures are potentially useful for orthopedic implants, storage of biological agents for controlled release, and solar cell applications.

Hybrid micro/nano-topography of a TiO2 nanotube-coated commercial zirconia femoral knee implant promotes bone cell adhesion in vitro.

Various approaches have been studied to engineer the implant surface to enhance bone in-growth properties, particularly using micro- and nano-topography. In this study, the behavior of osteoblast (bone) cells was analyzed in response to a titanium oxide (TiO2) nanotube-coated commercial zirconia femoral knee implant consisting of a combined surface structure of a micro-roughened surface with the nanotube coating. The osteoblast cells demonstrated high degrees of adhesion and integration into the surface of the nanotube-coated implant material, indicating preferential cell behavior on this surface when compared to the bare implant. The results of this brief study provide sufficient evidence to encourage future studies. The development of such hierarchical micro- and nano-topographical features, as demonstrated in this work, can provide insightful designs for advanced bone-inducing material coatings on ceramic orthopedic implant surfaces.

Biomaterials and Biotechnology Schemes Utilizing TiO2 Nanotube Arrays

Ti and Ti alloys are corrosion resistant, light, yet sufficiently strong for utilization as loadbearing and machinable orthopaedic implant materials. They are one of the few biocompatible metals which osseo-integrate, provides direct chemical or physical bonding with the adjacent bone surface without forming a fibrous tissue interface layer. For these reasons, they have been used successfully as orthopaedic and dental implants (Ratner 2004). To impart even greater bioactivity to the Ti surface and enhance integration properties, surface treatments such as surface roughening by sand blasting, formation of anatase phase TiO2 (Uchida et al. 2003), hydroxyapatite (HAp) coating, or chemical treatments (Ducheyne et al. 1986; Cooley et al. 1992) have been employed. However, these treatments are generally on the micron scale. Webster et al. (Webster et al. 2001; Webster, Siegel, and Bizios 1999) reported that it is even more advantageous to create nanostructured, in particular in the less than 100nm regime, surface designs for significantly improved bioactivity at the Ti implant interface and for enhanced cell adhesion. Since then, advances in biomaterial surface structure and design, specifically on the nanoscale, have improved tissue engineering in general. This chapter is a report on titanium dioxide (TiO2, or Titania) nanotube surface structuring for optimization of titanium (Ti) implants utilizing nanotechnology. The main focus will be on the unique 3-D tube-shaped nanostructure of TiO2 and its effects on creating profound impacts on cell behavior. We will also shed light on the effects of changing the nanotube diameter size and optimizing the geometry for enhanced cell behavior. This work focuses on the tissue specific areas of cartilage and bone. Specifically, we will discuss how the desired cell behavior and functionality are enhanced on surfaces with TiO2 nanotube surface structuring. Here we reveal how the TiO2 surface nanoconfigurations are advantageous in various tissue engineering and regenerative medicine applications, for osteo-chondral, orthopedic, and osteo-progenitor implant applications discussed here and beyond. This chapter will also shed light on future applications and the direction of nanotube surface structuring.

Nanocomposites of TiO2 and double-walled carbon nanotubes for improved dye-sensitized solar cells

It is demonstrated that an incorporation of double-walled carbon nanotubes (DWCNTs) into a TiO2 photo-anode layer results in a significant improvement in the overall energy conversion performance in the dye-sensitized solar cell (DSSC). Comparing to the standard TiO2 anode, the carbon nanotube-containing TiO2 anode with 0.2 wt. % DWCNTs has boosted up the photocurrent density (Jsc) by 43%. The DSSC power conversion efficiency was also improved from ∼3.9% in the case of carbon nanotube-free TiO2 anode to as high as 6.4% with the addition of DWCNTs upon optimized anode annealing. The observed enhancement in the solar cell performance in the presence of the carbon nanotubes is attributed primarily to the noticeable reduction in microcracking and associated robust electrical conduction. Some contribution of the electrical conducting nature of the filler material (DWCNTs) to the improved DSSC properties may be possible; however, it is viewed as a minor effect, considering the small amount of the nanotubes used.

Fabrication of thin film TiO2 nanotube arrays on Co-28Cr-6Mo alloy by anodization.

Titanium oxide (TiO2) nanotube arrays were prepared by anodization of Ti/Au/Ti trilayer thin film DC sputtered onto forged and cast Co-28Cr-6Mo alloy substrate at 400 °C. Two different types of deposited film structures (Ti/Au/Ti trilayer and Ti monolayer), and two deposition temperatures (room temperature and 400 °C) were compared in this work. The concentrations of ammonium fluoride (NH4F) and H2O in glycerol electrolyte were varied to study their effect on the formation of TiO2 nanotube arrays on a forged and cast Co-28Cr-6Mo alloy. The results show that Ti/Au/Ti trilayer thin film and elevated temperature sputtered films are favorable for the formation of well-ordered nanotube arrays. The optimized electrolyte concentration for the growth of TiO2 nanotube arrays on forged and cast Co-28Cr-6Mo alloy was obtained. This work contains meaningful results for the application of a TiO2 nanotube coating to a CoCr alloy implant for potential next-generation orthopedic implant surface coatings with improved osseointegrative capabilities.