Hyaluronic acid is widely used in the treatment of osteoarthritis and exerts significant chondroprotective effects. The exact mechanisms of its chondroprotective action are not yet fully elucidated. Human articular chondrocytes actively produce reactive oxygen and nitrogen species capable of causing cellular dysfunction and death. A growing body of evidence indicates that mitochondrial dysfunction and mitochondrial DNA damage play a causal role in disorders linked to excessive generation of oxygen free radicals. We hypothesized that the chondroprotective effects of hyaluronic acid on oxidatively stressed chondrocytes are due to preservation of mitochondrial function and amelioration of mitochondria-driven apoptosis. When primary human chondrocyte cultures were exposed to reactive oxygen or nitrogen species generators, mitochondrial DNA damage along with mitochondrial dysfunction and mitochondria-driven apoptosis accumulated as a consequence. In addition, cytokinetreated primary human chondrocytes showed increased levels of mitochondrial DNA damage. Pretreatment of chondrocytes with hyaluronic acid caused a decrease of mitochondrial DNA damage, enhanced mitochondrial DNA repair capacity and cell viability, preservation of ATP levels, and amelioration of apoptosis. The results of these studies demonstrate that enhanced chondrocyte survival and improved mitochondrial function under conditions of oxidative injury are probably important therapeutic mechanisms for the actions of hyaluronic acid in osteoarthritis.

The synthesis of one-dimensional metal nanostructures can be achieved through the use of DNA molecules as templates to control and direct metal deposition. Copper nanostructures have been fabricated using this strategy, through association of Cu(2+) ions to DNA templates and reduced with ascorbic acid. Due to the possibility that the reduction of the Cu(2+) can result in the preferential formation of Cu(2)O over metallic Cu(0), X-ray photoelectron spectroscopy and X-ray diffraction have been carried out to establish the chemical identity of the nanostructures. Conclusive evidence is found that reduction of the Cu(2+) ions does result in the formation of the desired metallic Cu(0) structures. The morphology of the nanostructured Cu(0) material has also been observed by atomic force microscopy, showing the structures to have a "beads-on-a-string" appearance and being 3.0-5.5 nm in height. The electrical properties of the structures have been investigated by scanned conductance microscopy, showing the Cu(0) structures exhibit much larger electrical resistance than expected for a metallic nanowire. This is thought to be a consequence of their "beads-on-a-string" morphology and small lateral dimensions (sub-10 nm); both these factors would be expected to increase the electron scattering rate, and, further, there are likely to be significant tunneling barriers at the Cu(0) particle-particle junctions.

Details of the mechanism of formation of supramolecular polymer nanowires by templating on DNA are revealed for the first time using AFM. Overall these data reveal that the smooth, regular, structures produced are rendered by highly dynamic supramolecular transformations occurring over the micrometre scale. In the initial stages of the process a low density of conducting polymer (CP) binds to the DNA as, essentially, spherical particles. Further reaction time produces DNA strands which are more densely packed with particles giving a beads-on-a-string appearance. The particles subsequently undergo dynamic reconfiguration so as to elongate along the template axis and merge to yield the highly regular, smooth morphology of the final nanowire. MD simulations illustrate the early stages of the process showing the binding of globular CP to duplex DNA, while the latter stages can be modeled effectively by a linear thermodynamic description based on the balance between the line energy, which accounts for adhesion of the material to the template, and its surface tension. This model accounts for the phenomena observed in the AFM studies: the relative success of DNA templating of polymers compared to metals; the slow approach to equilibrium; and the observed thinning and 'necking' phenomena as the structures transform from beads-on-a-string to smooth nanowire.

DNA-templating has been used to create nanowires from metals, compound semiconductors and conductive polymers. The mechanism of growth involves nucleation at binding sites on the DNA followed by growth of spherical particles and then, under favourable conditions, a slow transformation to a smooth nanowire. The final transformation is favoured by restricting the amount of templated material per unit length of template and occurs most readily for materials of low surface tension. Electrical measurements on DNA-templated nanowires can be facilitated using three techniques: (i) standard current-voltage measurements with contact electrodes embedded in a dielectric so that there is a minimal step height at the dielectric/electrode boundary across which nanowires may be aligned by molecular combing, (ii) the use of a dried droplet technique and conductive AFM to determine contact resistance by moving the tip along the length of an individual nanowire and (iii) non-contact assessment of conductivity by scanned conductance microscopy on Si/SiO2 substrates.