An injectable biomaterial developed by University of Sydney engineers could provide an alternative to the painful treatments currently available for serious burns.
More than 10,000 people are hospitalised each year with severe burn injuries. What makes this situation more challenging is that burn wounds are not easy to treat.
Clinicians have to debride or remove the burned tissue and insert scaffolds, over which they place skin grafts.
On average, this painful surgical treatment has to be repeated almost four times, because the grafts can open up and don’t heal right away.
When Dr Ali Fathi was studying chemical engineering at the University of Sydney, he was among those who realised the constraints of the traditional approach towards tissue engineering. Many clinicians also concluded that making tissue outside and implanting it in the body had significant clinical and commercial limitations.
“I didn’t like the concept because I could see the challenges with open surgery, moving engineered tissue into the body, and the costs associated with it,” Fathi explains. “Instead, we need to use the innate ability of our bodies to regenerate and repair different tissues.”
The missing piece in this puzzle was an injectable and regenerative biomaterial.
Fathi brought his engineering mindset to this problem and set up Tetratherix, where he is Chief Technology Officer. At the outset, he identified four key attributes to engineer an optimal biomaterial: it must be injectable, it must form a hydrogel in the patient’s body, it should stay in place, and it should then degrade over time.
“I combined four monomers or building blocks with these properties and made a polymer,” he explains. “I did that during my PhD and patented the technology.”
Tetratherix holds patents in the US, Australia, Japan and several European countries. The company has filed additional patents for specific chemical compositions of the polymer and their applications.
Towards the end of his PhD, Fathi met Terence Abrams, who was also finishing his chemical engineering degree at the University of Sydney. Abrams, who is now Tetratherix’s Chief Operating Officer, was impressed with the technology and, together, the two formed the biotech company, converting an empty warehouse in the Sydney suburb of Alexandria into a clean-room production facility.
The next level
Moving from traditional research to commercial activity threw up some challenges, particularly concerning regulatory compliance and manufacturing at scale.
“Because the product is an injectable medical device, there are very specific standards which are quite nuanced,” explains Abrams. “Ali and I had to write the first version of our quality management system from scratch — hundreds of pages of documentation, including standard operating procedures, protocols, logs and records.”
Scaling up production for volume was another hurdle for the team.
“When Ali was producing the polymer at the university lab, he was making a gram at a time,” recalls Abrams.
To become a viable commercial venture, they needed to transition — operations and yield — by orders of magnitude and produce hundreds of grams per batch.
The duo drew on its chemical engineering training, newly acquired ISO knowledge and an understanding of the validation requirements to overcome the problem.
“We’ve now got our own production facility, which I believe is something quite rare in a biotech company like ours,” says Abrams.
The four monomers are the key components. “We synthesise one of the macro-monomers ourselves while the other three are purchased off the shelf,” explains Abrams.
Once the synthesis of the first macro-monomer is complete, the team synthesises the final product, TetraMatrix, which is a smart thermoresponsive polymer.
“That involves free radical polymerisation, whereby we add the four monomers plus the initiator in a solvent, and we leave it under nitrogen at moderate temperature for 18 to 24 hours,” says Abrams.
“Out of that, we get the crude polymer solution, which needs to be purified.”
The original purification process used diethyl ether, which presented problems in terms of biocompatibility and safety. Diethyl ether is highly explosive.
So the team moved to water purification. In this process, the polymer is precipitated in water, resulting in purified polymer gel. It is then lyophilised, or freeze dried, to remove water and allow bulk storage.
“When we require devices to be made, the dried polymer is reconstituted in water, packed into syringes and sent for gamma radiation to ensure sterility,” adds Abrams.
The name, Tetratherix, nods to the TetraMatrix’s four properties; with “tetra” commonly used as a prefix in chemistry.
“The second half of the name comes from ‘therapeutics’ and ‘matrix’, as that’s the way we operate,” explains Ali.
The end product is synthetic and does not contain animal or human-derived components.
“That makes our processing and our production very cost effective,” says Fathi.
“We are providing a cost-effective solution as we are preventing the need for multiple surgical interventions.”
No surgery required
Fathi explains that after removing damaged tissue or foreign objects from a wound, the product can be poured. The liquid polymer turns into hydrogel when it makes contact with the body and forms a moldable scaffold within the wound area.
This scaffold provides a matrix for the wound bed to grow within and achieve wound closure without the need for surgical intervention.
The technology has been rigorously tested in multiple preclinical studies, and the company has also successfully completed a pilot clinical trial.
The development program is now centred on the use of TetraMatrix for wound healing in burns patients.
The company has completed a large animal study to treat challenging wounds that reflect real life clinical conditions.
“Our next step is to run clinical trials at a major burn centre in Sydney, and following that, registration in the US, followed by Europe and Australia,” says Abrams.
The regulatory process in the US is well defined and the team aims to get its first product for wound management into that market by the end of 2024, with Australia and other regions to follow.
Fathi and Abrams are dreaming big and are confident they have a revolutionary product in their hands. “We will treat 10 million people in the next 10 years,” says Fathi.
Regeneration site
At room temperature, TetraMatrix is a liquid polymer. A synthetic material, it can be dissolved in a saline solution, loaded into sterile syringes and sent out to clinicians for use. Upon injection to the body, it forms a hydrogel — a structure with chewing gum consistency.
This allows cells to grow within it, regenerating the tissue into which the product is injected. TetraMatrix is reabsorbed into the body over time, breaking down into non-toxic components and leaving healthy tissue behind at the site.