When Professor Hala Zreiqat asked for a patent to be filed on her work, the commercial arm of her university wavered.
Zreiqat issued an ultimatum. Either they filed by 5pm that Friday, or she would go to the bank, get the money, and do it herself.
The patent was filed two minutes before the deadline.
It was for a world-first synthetic bone substitute, which can be personalised for each patient and manufactured using a 3D-printer. Created by Zreiqat from the Faculty of Engineering at the University of Sydney, it’s launched a new era in orthopaedics. Within two decades or less, the need for plates, screws, endless surgeries, and frantic searches for bone donors, may be over.
A bone breakthrough
Born in Jordan, Zreiqat comes from a family with a passion for education. “I was supported financially and emotionally by the most beautiful, wise parents,” she told The Brilliant. She wanted to study interior design, but to do so, she would have had to move to the UK.
“I did not want to go, because we were not rich at all,” says Zreiqat. “So I thought, no, I’m not going to be greedy. I will stay in Jordan and do science.”
Within a few years of graduating, she was a Scientific Officer at the Queen Alia Center for Heart Diseases, part of the renowned King Hussein Medical Center, Jordan. It was a prestigious job, and when Zreiqat arrived in Sydney in 1991, she discovered it wasn’t as easy to find such an interesting job. So she went knocking on researchers’ doors at the universities and offered to do voluntary work. One professor finally offered her a paid position in biomedical engineering. Soon, she enrolled in further study. “My PhD was in looking at how bone cells behave to modified orthopaedic implants,” she explains.
By 2000, Zreiqat was Acting Head of the Bone Biomaterial Unit in the Department of Pathology at the University of NSW, wondering if it were possible to create a substitute for bone.
Right now, when something goes wrong with bones and joints, surgeons implant titanium – a metal that can’t be corroded by bodily fluids, while also being flexible and strong. But it stays in the body for the lifetime of the patient.
Not only that, but a layer of titanium oxide will form on the surface; over time, with repeated friction, this top layer may release particles into surrounding tissues, causing inflammation. The metal also wears out; as Zreiqat says, some patients face as many as 10 surgeries in 10 years to replace failing implants.
“It is not enough to simply stay with the same limited twentieth century technologies,” says Zreiqat. “We want to develop the material that mimics the structure and architecture of bone and to maximise its function for each individual.”
Her PhD involving looking at the biological responses to titanium that had been modified to be more compatible with the body. But a better solution would be to find a material that will help regenerate the bone itself, while offering mechanical support until the new bone has grown.
The challenge is that bone is a complex material with an unusual suite of properties. “It’s as strong as cast iron, while remaining as light as wood,” says Zreiqat. “It’s highly porous, highly connected, highly alive, and highly vascular.” It’s permeable enough that blood, cells and nutrients can pass through it, but durable enough that it can withstand falls, blows and knocks.
Zreiqat’s solution was to create a ceramic scaffold that would not only provide structural support, but which was also porous and interconnective. The material needed to be bioactive, or able to interact with living systems, to foster the regrowth of natural bone, so Zreiqat imbued it with trace elements and other compounds.
And it worked.
“We did a whole host of pre-clinical studies, starting from small to large animal studies,” she says. “So far, the results are highly promising. We did not see any inflammatory reaction. We did not see any toxic reaction.”
If the ceramic becomes clinically available, patients will have a scan to determine the nature of their bone defect, and the necessary part will be 3D-printed in the correct size and shape. Zreiqat is hoping that, one day in the not too distant future, it will be possible to print parts of the jaw; until now, it has been an almost impossible part of the body to rebuild. And all of this will be done within two days, says Zreiqat.
The team has recently demonstrated that the ceramic appears to have other extraordinary properties; it seems to be so good at encouraging bone regrowth that it’s actually an ‘anti-senescence’ – or anti-ageing – material, says Zreiqat. “As you grow older, there will be improved capacity for regeneration of bone in an older population.”
Patent to market
After the patent was filed, Zreiqat knew she needed a company to bring it to market. She called a colleague an Australian company called Allegra Orthopaedics. He said, “The Board is meeting tomorrow at eight o’clock in the morning. Do you think you could come and present?”
“Absolutely,” she said. She made the case, and Allegra agreed to begin the process of negotiating with the university, to commercialise the ceramic. The team have already done pre-clinical animal trials, with promising results. The next step is to go through the many steps required to take a product to market, a process delayed by the COVID pandemic.
Although the ceramic has a long way and many tests to get through before it will be released, the scientific world was quick to recognise the magnitude of the breakthrough, and Zreiqat has since received an avalanche of awards: an Order of Australia; the 2018 New South Wales Premier’s Woman of the Year; the King Abdullah II Order of Distinction of the Second Class; a Eureka Prize; and a University of Sydney Payne-Scott Professorial Distinction. And this year, she has been awarded a Fulbright Scholarship to MIT in Boston, to develop a deeper understanding of how to commercialise research.
She and her team are also working on the rest of the musculoskeletal system. “We have also developed the next generation of tendon and ligament material,” she says. “We’re working towards validating this material in a pre-clinical animal model.”
It’s hard to overstate the magnitude of the bioengineering breakthrough. There are 2.2 million bone graft surgeries performed around the globe each year; 71,000 Australians get hip and knee replacements each year; and 3.9 million Australians – or one in six – suffer from arthritis as the cartilage in their joints erodes. The prospect that, one day, these patients could have an effective, permanent and personalised treatment is a tantalising one.
It won’t happen quickly – there are years of research and work ahead. But the work has begun.
Opening the doors for others
In 2016, Zreiqat received a one year fellowship from the Harvard Radcliffe Fellowship Program. While at Harvard, she began to think more about discrimination, and decided to do something about it.
She founded the IDEAL Society (the acronym stands for Inclusion, Diversity, Equity, Action, Leadership); it aims to establish a global network of women, with the goal of transforming society. “We’re working towards having ambassadors in each country.”
She also wants to do more to foster early-career researchers by ensuring that they have secure contracts. “Otherwise, we risk the exodus of these talented people. And then what happens? We don’t have people who will innovate.”
Challenges aside, Zreiqat is brimming with optimism about the future of science.
“In Australia we’re getting more and more funding available for science,” she says. And she’s getting more and more opportunities to further her research. Today, companies are beating a path to her door, wanting to collaborate with her and her team, and there’s no question of paperwork being left to the last minute.
“It’s beautiful,” she says.
Article by Felicity Carter
Photo Credit: Photo supplied