Monday, April 10, 2006

Nano-scaffolds could help rebuild sight

ANIMALS blinded following damage to their optic nerve have had their vision partially restored with the help of an implanted nanoscale scaffold that has encouraged nerve tissue to regrow. The technique, likened by its inventors to the way a garden trellis encourages the growth of ivy, holds out the hope that people with diseased or injured optic nerves might one day recover their sight.

The optic nerve, which connects the eye to the brain, can be severed by traumatic injuries such as those suffered in car crashes. It can also be damaged by glaucoma, when excessive pressure in the eyeball causes tissue at the back of the eye to collapse, pulling nerve fibres apart and so causing progressive loss of vision.

Repairing the optic nerve requires the long, spidery branches of nerve cells, called axons, to grow again and reconnect. Achieving this is a "formidable barrier", says Rutledge Ellis-Behnke, a biomedical engineer at the Massachusetts Institute of Technology. Axons can be encouraged to lengthen by exposing them to growth factors, but they rarely extend far enough to bridge the gaps typical of most optic nerve injuries, he says.

To overcome this, Ellis-Behnke and colleagues from Hong Kong University and the Institute for Neuroscience in Xi'an, China, created a nerve-bridging scaffold, made up of nanoparticle fibres. They made these fibres the same size as the sugar and protein complexes on the surface of the torn axon, in the hope that this would encourage cell growth and migration (Proceedings of the National Academy of Sciences, DOI: 10.1073/pnas.0600559103).

To make their scaffold, the team turned to a discovery from the early 1990s by Shuguang Zhang at MIT. He found that certain peptide sequences can be made to self-assemble into mesh-like sheets of nanofibres by immersing them in salt solutions at similar concentrations to those found in the body.

To test whether this would help nerves to regenerate, the team took hamsters whose optic nerves had been deliberately severed and injected a peptide mixture into each animal's brain close to the injury site. After six weeks, the animals had recovered some of their vision. "They could see well enough to find their food, to function well," says MIT team member Gerald Schneider.

Schneider estimates that 30,000 axons had reconnected, compared with only around 30 in previous experiments using other approaches such as nerve growth factors. The scaffold appears to eventually break down harmlessly.

Tissue engineer Kevin Shakesheff at the University of Nottingham, UK, says the work is exciting, but urges caution. The surgical cut made in the hamster's nerve is not representative of "more messy" injury or disease in people, he warns, and other central nervous system work has shown that species differences mean nerve regeneration in a rodent might not translate into humans.

Shakesheff also notes that it remains unknown how the scaffold regenerates tissue, and that it might ultimately be possible to use stem cells to further boost the regenerative response.

The MIT team now plans to extend the work in the hope of developing therapies for spinal cord injuries.
>From issue 2543 of New Scientist magazine, 18 March 2006, page 30
What vaccine design can take from bones

Another type of nanotechnology is exploiting the way the body removes bone fragments to deliver waterproof, timed-release payloads of vaccines that would break down if not kept dry prior to release. The vaccine, enclosed in mineral spheres, could be injected as a follow-up booster dose at the same time as the initial dose.

The spheres, developed by Cambridge Biostability (CBL) in the UK, are made of calcium phosphate, the main mineral constituent of bone. Cells called osteoclasts mistake them for stray pieces of bone and dissolve them, causing them to release their contents over a period of months.

To build the spheres, a mixture of vaccine and calcium phosphate crystals within an aqueous solution is sprayed out of a nozzle into a stream of gas at around 170 °C. The nanocrystals are surrounded by a cloud of water molecules, which evaporate in the gas. As the water molecules are removed, the nanocrystals draw closer together until they partially fuse to form solid glassy spheres 5 micrometres in diameter, with the vaccine embedded inside. The heat of the gas is absorbed by evaporative cooling before it destroys the vaccine, says Bruce Roser of CBL.

The microspheres protect the vaccine from water in the body, allowing them to be used even with delicate payloads such as meningitis vaccine, which is damaged by prolonged contact with water.

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