Physicist Awared $600,000 NHMRC Grant

25 October 2011

Despite steady improvement over the last three decades, cardiovascular disease remains one of the biggest causes of death in Australia and continues to generate a considerable burden on the population in terms of illness and disability.

In recent years approximately 3.5 million of Australians have reported having a long-term cardiovascular condition (source ABS) and this figure is likely to increase given the prevalence of ageing baby-boomers.

Yet to date there is a lack of cardiovascular devices that are clinically effective and fundamentally biocompatible. Currently implantation of vascular stents can cause inflammation leading to complications such as thrombosis and neointimal hyperplasia that can be fatal.

A team of University of Sydney researchers have been awarded a NHMRC Grant of $606,325 over three years to develop a stent technology that can simultaneously address the problems of restenosis and thrombogenicity and provide fundamental biocompatibillity.

The researchers plan to utilise a platform technology developed by Professor Marcela Bilek and Professor David McKenize in the School of Physics, to revoluntionise implantable stents. Their research findings were published in the August issue of Proceedings of the National Academy of Sciences*.

CAPTION: The schematic (top, left) shows a protein molecule in its native conformation (black hydrophilic residues concentrated on the inside) immobilized on the coating by a covalent bond. Theoretical curves plotted (top, right) along with experimental data show that the covalent immobilization occurs in two steps: the first is physical adsorption (blue curve) and the second is the formation of a covalent bond with a unpaired electron that has migrated to the surface (red curve). The process is illustrated schematically in the inset. Stainless steel coated with the protein-binding surface shows a dramatic reduction in its propensity to induce blood clots when exposed to flowing blood (insets at bottom). The uncoated stainless steel adheres platelets and fibrinogen fibrils, the precursors to blood clots (bottom, left) while the coated steel sheet adheres a layer of covalently attached protein molecules (bottom, right). Scale bars are 20 micrometers.

"We have developed a coating that covalently immobilizes protein molecules that come into contact with it. Our strategy is to use it to provide a fundamentally biocompatible cloak of strongly attached native biological molecules for the stent," says Professor Bilek.

Professor Bilek says a major problem with coatings on stents is delamination. The group has worked hard to develop a nanostructured interface that provides excellent adhesion even at locations that experience major deformation upon stent expansion.

"The cloaking layer of protein could come from the patient's own body upon implantation or alternatively be attached prior to implantation," says Professor Bilek.

"Our preliminary studies indicate that tropoelastin, the extra cellular matrix protein making up the elastic component of tissues, is a good candidate. It encourages natural healing whilst inhibiting resentosis and thrombosis. The NHRMC grant will allow us to further develop this breakthrough research."

Professor Bilek says that further research will potentially lead to the development of truly biocompatible materials for a wide range of vascular applications.

The NHMRC grant was awarded to the research team comprising of Professor Marcela Bilek, School of Physics, Professor Martin Ng, Royal Prince Alfred Hospital and Professor Anthony Weiss, School of Molecular Biosciences.

*The paper: Free radical functionalization of surfaces to prevent adverse responses to biomedical devices by Marcela M. M. Bilek (School of Physics, SoP), Daniel V. Bax (SoP), Alexey Kondyurin (SoP), Yongbai Yin (SoP), Neil J. Nosworthy (SoP), Keith Fisher (School of Chemistry), Anna Waterhouse (School of Molecular Bioscience, SMB), Anthony S. Weiss (SMB), Cristobal G. dos Remedios, and David R. McKenzie (SoP). All authors are from the University of Sydney, is published in the prestigious journal Proceedings of the National Academy of Sciences, USA.

Contact: Alison Muir

Phone: 02 9036 5194

Email: 1b1405001d2f17591d230677070827140a341b09311d792218