Although the reasons for enhanced osteoblast functions on nanostructured materials are under intense investigation, the evidence that osteoblasts perform better on nanostructured surfaces is overwhelming. As one example, osteoblast responses to carbon nanotubes (CNTs) have been studied. Due to their excellent electrical conductivity, great mechanical strength, and unique chemical-biological properties (Iijima 1991; Lin et al. 2004; Webster et al. 2004; Smart et al. 2006; Zanello 2006), many studies have shown that CNTs are promising for bone sensor applications.
CNTs are macromolecules of carbon, classified as single walled carbon nanotubes (SWCNTs), diameter 0.4-2 nm, and multiwalled carbon nanotubes (MWCNTs), diameter 2-100 nm. In theoretical and experimental results, CNTs have an electric-current-carrying capacity 1,000 times higher than copper wires (Avouris et al. 2003). Thus, CNTs have been considered to improve the electrical properties of such sensors as well. For instance, CNT-TiN nanocomposites, composed of 12% CNTs by volume, exhibited a 45% increased electrical conductivity over TiN materials (Jiang and Gao 2005). Since bone regenerates under electrical conduction, many researchers have used CNTs to promote bone growth. For example, nano-composites of polylactic acid and MWCNTs have been shown to increase osteo-blast proliferation by 46% and calcium production by greater than 300% when an alternating current was applied to the substrate in vitro (Supronowicz et al. 2002).
Also, CNTs have been used to increase the mechanical strength of nanocompos-ite scaffolds for bone tissue engineering. SWCNTs, functionalized with phosphates and poly(aminobenzene sulfonic acid), can substitute as collagen to direct the anisotropic crystallization of hydroxyapatite (HA) reaching a thickness of 3 mm after 14 days of mineralization, resulting in composites that can be used as supporting scaffolds for orthopedic applications (Zhao et al. 2005). MWCNTs improve the mechanical properties of the as-aligned HA composite coatings (Chen et al. 2007). Balani et al. (2007) showed that a MWCNT reinforced HA coating promoted human osteoblast proliferation in vitro compared to a normal HA coating, and osteoblasts were observed near MWCNTs regions.
CNTs exhibit a large surface area to volume ratio, which may support and promote cell attachment. It has been investigated that a large number of human osteoblasts adhered more on carbon nanofiber (CNF) micro-patterns than polycarbonate urethane (Khang et al. 2006). The morphology of osteoblasts extended in all directions within CNT scaffolds formed on polycarbonate membranes (Aoki et al. 2005). Nanophase poly(lactic-co-glycolic) acid (PLGA) casts of CNF (average diameter=60 nm) compacts possessed a higher degree of nanometer surface roughness by approximately 50%, which increased osteoblast adhesion after 1 h compared with PLGA casts of conventional CNFs (average diameter=200 nm) (Price et al. 2004).
Moreover, osteoblast-like cells also significantly enhanced their adhesion on vertically aligned MWCNTs arrays on substrates (another great sensor), which were prepared by lithography. It was observed that the periodicity and alignment of vertically aligned MWCNTs considerably influenced the growth, shape, and orientation of the osteoblasts (Giannona et al. 2007). Zanello also showed that single/ multi-walled CNTs scaffolds with/without surface modifications are suitable for osteosarcoma ROS 17/2.8 cell proliferation. Lastly, the cell densities and transforming growth factor-b1 secreted by human osteoblast-like (Saos2) cells were higher on MWCNT scaffolds compared with polystryrene and polycarbonate scaffolds.
Importantly, in the studies mentioned above, CNTs were synthesized by a number of different techniques, yet all showed greater osteoblast functions. CNTs can be produced by a laser furnace, the arc, and chemical vapor deposition (CVD). However, CVD is a scalable and controllable method to obtain high purity CNTs. Sato et al. (2005) revealed that cobalt (Co) particles could extend their catalytic ability by combining with Ti particles when growing MWCNTs by CVD and forming a strong contact between Ti and MWCNTs. All of these techniques speak well for creating a sensor composed of electrically active CNTs that can also positively interact with bone cells.
Importantly, for such sensor design, cell responses transduce and transmit a variety of chemical and physical signals to produce specific substances and proteins within specific tissues and organs. The in situ sensing of proteins from specific cell induction processes can be employed as a signal of specific cellular responses or bone regeneration. For example, in a previous study, MWCNTs grown by the CVD technique out of anodized Ti nanotubes (Fig. 4) exhibited excellent electrochemical properties and stability. An in vitro study showed the redox of proteins could be enhanced on MWCNTs grown from an anodized nanotubular Ti (MWCNT-Ti) electrode in order to sense bone growth (Sirivisoot et al. 2007; Sirivisoot and Webster 2008), and such a sensor can promote osteoblast proliferation and differentiation after 21 days on MWCNT-Ti. MWCNT-Ti can thus be used as a bio-sensing material to generate electrical signals, which can be interpreted later as information.
Moreover, coupling drug delivery to implantable wireless sensors enables on-command diffusion-controlled drug delivery systems by using radio-frequency, which is a new approach in the orthopedic field. There is a need for new technology for the delivery of soluble/insoluble or stable/unstable therapeutic compounds locally to improve the bioavailability of drugs. Polypyrrole is a conductive electro-active polymer, which has been shown to be biocompatible and has been proposed
Fig. 4 SEM micrographs of multiwalled carbon nanotubes (MWCNTs) grown out of an anodized nanotubular surface: (a) currently implanted conventional titanium (Ti) which has no sensing capabilities; (b) anodized nanotubular Ti which has no sensing abilities; and (c) side and (d) top views of MWCNT grown out of anodized nanotubular Ti which has bone growth sensing abilities
Fig. 4 SEM micrographs of multiwalled carbon nanotubes (MWCNTs) grown out of an anodized nanotubular surface: (a) currently implanted conventional titanium (Ti) which has no sensing capabilities; (b) anodized nanotubular Ti which has no sensing abilities; and (c) side and (d) top views of MWCNT grown out of anodized nanotubular Ti which has bone growth sensing abilities for several in vivo applications, such as a conductor for the electrical stimulation of cells. PPy can be synthesized on Ti for local drug delivery, promoting bone regeneration, and carrying therapeutic drugs. Typical doses of antibiotic/anti-inflammatory drugs need to be large for hip/knee implants. Improvement in the delivery efficiency and localization may also result by controlling the thickness and the area of the polypyrrole membrane. Thus, sensors are being developed that can sense new bone formation, and if that is not happening, release drugs to promote new bone growth. Similar attempts are being attempted for decreasing orthopedic implant infection and inflammation.
In summary, this exciting new nanomaterial, or CNTs, may become a powerful tool in bone sensor applications in terms of their nanofeatures, superior mechanical properties, and higher electrical conductivity to sense and control cellular behavior. Continuing the careful studies on CNTs may discover additional potentials for this novel biomaterial for engineering biocompatible nanomaterials and nanodevices for various sensor applications.
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