ÁñÁ«ÊÓƵapp

When Professor Gordon Wallace started in the materials science field 30 years ago, he thought somebody else would work out how to make the new materials. When nobody came forward, he realised he was going to have to do it himself.

That was the start of a new way of thinking - revolution is not too strong a word - that is quickly leading us into the world of miraculous science fiction, where organs can be produced via 3D printing, where quadriplegics can walk again, where schizophrenia or Parkinson's become diseases as distant as the plague.

While some of these things are not yet possible, the trajectory of the last five years at the  (ACES) is so steep that possibility quickly becomes probability.

"I wouldn't be game to say there's something that's just not possible," Professor Wallace says. "It may take some time and some genius but we've got that genius in the next generation of researchers that are coming through." 

Revolution in the making

As director of a centre that employs 120 researchers in ÁñÁ«ÊÓƵapp, and 120 more spread out across Australia, Professor Wallace has an infectious enthusiasm, coupled with an engaging humility, spoken in a Northern Irish brogue that has resisted decades of calling Australia home.

It's easy to see why people want to work with him. He sees himself as an old-timer, someone who came to the field 30 years ago, when materials science was all about big buildings, big manufacturing plants, big and capital-intensive projects.

More than that, the field was run by economists and accountants, where things had to be made the same so economies of scale made them cheap, where it was about "subtractive manufacturing", where you get a material, chisel out a shape, and join different materials together to form an object.

The arrival of 3D printing changed all of that.

"For tens of thousands of dollars, you could create a fabrication facility wherever you wanted it, even in your own laboratory, which is exactly what we did" - Professor Gordon Wallace

Although the technique has been around for three decades, the explosion in applications only started around five years ago, and there's a sense at ACES that we're still very much in that explosive, early period of The Big Bang.

"Three-D printing really changed that because it meant that not only could we build with a wider range of materials, but we could build with very low investment of capital," Professor Wallace says.

"For tens of thousands of dollars, you could create a fabrication facility wherever you wanted it, even in your own laboratory, which is exactly what we did."

The technique involves printing a structure in layers with a custom-made printer using a wide range of materials from titanium and stainless steel right through to polymers and very soft gels that are 90 per cent liquid. There's no other manufacturing process that in a single run could accommodate materials with such different properties. 

From car parts to diabetes

The technique is already being used for car parts, car engines, airplane parts, but it's in the bio-medical space that some of the most exciting developments are taking place. The centre is working with clinicians across Australia to develop a range of applications.

So opthamologist Dr Michael Coote had dreamed up - and designed - implants for his glaucoma patients to regulate pressure in the eye through controlling fluid movement.

The team at ACES were able to make his vision a reality literally overnight, bio-printing a number of different prototypes in one run.

Or Professor Toby Coates is working with the centre with the challenge to bio-print cells for implantation, but within a polymer structure that protects and nourishes those cells. These can then grow to produce insulin, and help treat diabetes.

^{The ACES-developed Biopen is a handheld 3D printer that can be used in surgery to repair damaged cartilage. Photo: Paul Jones}

The need for a better solution

Ear nose and throat surgeon Dr Payal Mukherjee is already using 3D printing for demonstration and modelling purposes, but is confident that research will progress to printing stem cells. The current treatment for children born without ears is to take cartilage from the rib area and then implant that under the skin, where the ear should be.

The procedure is problematic for a number of reasons - taking the cartilage can cause medical complications, and implanting does not always work. "There is a need for a better solution," Dr Mukherjee says.

She teamed up with Dr Wallace's team last year and currently uses 3D printing for four main areas - pre-planning operations, demonstrating the result of operations to patients, developing prosthetic ears, and for education.

Her current research is looking at optimising the scaffold for a replacement ear, using PCL (a bio-compatible material) and hydrogel, which carries, protects and nourishes the cells.

But what really excites her is the next stage of the research, where she hopes to start experimenting with the stem cells from patients, using them in a hospital setting to create a living, growing organ for patients.

She sees the current stage of her research as - in part - giving clinicians the experience necessary in the technology of 3D printing so they are able to take the next step. "The fact that we are doing that now enables us to translate the bio-printer quicker in a clinical setting," she says.

Breaking down the barriers

Key to the rapid expansion of 3D printing into the bio-medical area is the breaking down of silos among disciplines. At the ACES headquarters at the ÁñÁ«ÊÓƵapp of ÁñÁ«ÊÓƵapp's Innovation Campus, there are material scientists talking to clinicians, and biologists talking to mechatronic engineers.

This is what brought human stem cell specialist and ACES Chief Investigator Associate Professor Jeremy Crook from Melbourne to ÁñÁ«ÊÓƵapp. "This is such a dynamic environment and has meant that my work has been able to move into all sorts of areas that it wouldn't have been able to otherwise," Professor Crook says.

"Being able to apply the stem cell biology to the materials engineering means I can do so much more with those cells both in terms of research and in terms of therapeutic interests."

"By building a tissue that is much more similar to 3D brain tissue, we can better understand the development of the tissue and interaction of drugs with the tissue" - Professor Jeremy Crook

With a background in neuro-chemistry, Professor Crook moved between the private sector in Singapore - developing stem cells for therapeutic application and drug research - and then back into academic research.

His latest work involves neural tissue engineering, where he takes an adult cell from a donor - it could be a skin cell - and reprogramming it back into a stem cell by overexpressing various proteins.

That cell can then be differentiated into any of the 200 types of cell in a human body.

Seaweed and crab shell

By taking these cells and mixing them with a material made from extractions of seaweed and crab shell, he can form a "bioink" able to be 3D-printed and converted into a tissue with a very low level of immune rejection.

Also, the materials used in the bioink are already approved by regulators for clinical use, thus streamlining costly approvals processes.

By combining the materials in certain concentrations, the fragile cells are protected during what Professor Crook calls "the rough and tumble" of the printing process. While directly printing cells into a human patient is still in the future, he has no doubt that it will become possible.

"It is certainly an aspiration that we have," he says. "In the interim, we are using the tissues for research, to investigate the development of the tissues, and using them for drug screening.

"By , rather than more conventional 2D cell cultures, we can better understand the development of the tissue and interaction of the drugs with the tissue."

^{The ACES team are 3D-printing artificial brain tissue to investigate the effect of drugs and explore brain disorders. Photo: Paul Jones} 

Bio-printing neural tissues

So if Professor Crook obtains cells from a patient with schizophrenia, he can test the efficacy of new drugs on real human tissue without the ethical barriers, or the complications of using non-human tissues.

He already receives inquiries from patients who could one day benefit from the research. Although not yet, he tells them, there's little doubt that the technology will eventually be applied for therapy.

"Working at the cutting edge of science is the most satisfying aspect of the job," Professor Crook says. "It's a dynamic area and it doesn't come without its challenges, one of which is funding. We're always looking for funding.

"We are making a difference, we are engaged in research that provides new knowledge of who and what we are, and potentially generate new treatments for currently intractable health problems. It’s an exciting space to be in" - Professor Jeremy Crook

"We are making a difference, we are engaged in research that provides new knowledge of who and what we are, and potentially generate new treatments for currently intractable health problems. It's an exciting space to be in."

The work is already coming to global attention, with customised printers being developed for a big orthopaedic research clinic in Italy and another for one of the largest medical research institutes in South Korea.

In developing such printers, each party has to understand enough about the other to be able to co-operate on a design of printer, material, and ultimately, on purpose.

^{Katharina Schirmer Using hydrogel material with cells and growth factors, ACES researcher Katharina Schirmer is developing a method to fabricate 3D conduits that help damaged nerves to reconnect. Photo: Paul Jones}

Nothing is impossible

"We've transformed a whole new generation of researchers who are thinking differently," Professor Wallace says. "I keep saying to my group of young researchers who are coming through now, that they will achieve more in the next five years than we did in the last 25. I really believe that.

"They are much better equipped in terms of their training, in terms of the environment and facilities that we have, particularly here in ÁñÁ«ÊÓƵapp. These are world-class and unique facilities.

"I wouldn't be putting my house on saying that anything is not going to be possible in five years' time, because I'm stunned at what we've been able to do in the last five years."