The brain and bone builders

The scaffolds used to support new buildings and buildings under repair are being recreated in miniature for use by the medical profession. These tiny scaffolds are being designed and created by Monash University researchers for implantation into the human body, where they would support and grow cells that could repair damaged brain or bone tissue. PENNY FANNIN reports.

Parkinson's disease affects up to 25,000 Australians, progressively making walking, talking and swallowing more difficult. The disease has no cure, although it has been suggested that if embryonic stem cells (cells that have the capacity to develop into any type of body cell) could be coaxed into becoming dopamine-producing nerve cells, then the effects of Parkinson's could be reduced or eradicated.

People with Parkinson's have low levels of dopamine -- a neurotransmitter that sends impulses from one nerve cell to another -- in their brains. This is because many of the nerve cells that produce dopamine have died. For the cells to be replaced, medical scientists need a suitable material on which to grow embryonic stem cells so they can be implanted into the body.

Designing ledges: Dr Karlis Gross and Ms Amanda Melville are among the only team in the world to have produced miniature ledges within a scaffold.

Researchers in Monash's School of Physics and Materials Engineering (SPME) have been creating scaffolds of synthetic and natural materials for this purpose and are focusing on whether stem cells that develop into dopamine-producing nerve cells will grow on them successfully.

Dr John Forsythe, a lecturer at SPME, says one of the most important characteristics for these scaffolds is an ability to direct stem cells along particular pathways and to degrade after they've been implanted.

With PhD researcher Ms Kylie Crompton, Dr Forsythe has been concentrating on developing a material that supports nerve cell growth and can be injected into the brain, eliminating the need for invasive surgery.

"As with keyhole surgery, only a small opening is needed to inject the scaffold and stem cells into the brain, a preferred minimally invasive surgery," Dr Forsythe says. "Once in the brain, it is hoped that the scaffold will act as a series of hitching posts that provide the right microenvironment for neurons to grow along and form connections. Once the new cells have made the right connections in the brain, the scaffold will degrade to prevent unfavourable immune responses."

Ms Crompton says that not only does the material need to be injectable and able to dissolve within a set time frame, it also needs to contain chemicals that help support and guide dopamine-producing nerve cells.

Building scaffolds: Dr John Forsythe and Ms Kylie Crompton are developing a material that supports nerve cell growth.

"The material we've designed, also known as a 'smart polymer', is quite neat. It's a liquid at room temperature, but as it heats up to body temperature it forms a gel. It's also biodegradable, so it can be broken down by the body within months," she says.

Ms Crompton's experiments have found that neural cells will survive on the material. She is now investigating whether the cells will move along a strip of the material, as they would need to when injected into a brain.

Two of their SPME colleagues, QEII research fellow Dr Karlis Gross and PhD researcher Ms Amanda Melville, are designing scaffolds for bone regeneration.

Natural bone contains hydroxyapatite, and Dr Gross and Ms Melville are working on designing hydroxyapatite-containing scaffolds that promote faster bone regeneration, can deliver anti-inflammatory drugs to the site of inflammation and can also be used to repair large segments of damaged bone.

"The need for bone replacement reaches tens of thousands of patients who have lost bone due to trauma, cancer or disease," Dr Gross says. "Currently, the best avenues for bone replacement involve bone from the patient or a donor; synthetic materials have also been used for small bone replacements. However, the limited supply of synthetic biomaterials has increased the waiting time for such operations, and larger synthetic porous scaffolds and stem cells offer great promise for regenerating bone in larger volumes."

The hydroxyapatite of natural bone is a calcium phosphate enriched with ions such as carbonate, fluoride, magnesium and zinc. Ms Melville is looking at how embryonic stem cells respond to hydroxyapatite containing these ions. Other studies have shown they have positive effects on bone growth and bone healing. She is also investigating at what rate an anti-inflammatory drug, ibuprofen, is released from material infused with these different ions.

Analyses at the Monash Institute of Reproduction and Development of mouse embryonic stem cells on hydroxyapatite doped with different fluoride levels have shown increased stem cell numbers and signs that they have begun to form tissue -- most likely bone.

Dr Gross says scaffolds for bone could be of two basic forms - the scaffold material could be 'seeded' with stem cells and implanted into the body by surgeons, or the surgeon could implant a scaffold with features that guide stem cells into the scaffold where they would lead to tissue formation.

Stem cell migration through the scaffold could be achieved with internal design features such as chemically enriched surfaces or tiny ledges that could attract and guide stem cells.

"When miniature ledges or grooves are incorporated into a scaffold, they offer promise for stem cell attachment and guidance along the walls of the scaffold," says Dr Gross.

His research team is the only group in the world to have produced miniature ledges within a scaffold.

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