Printing the Holy Grail

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A bioprinter that can grow human tissue and bone is on its way from Professor Saso Ivanovski A bioprinter that can grow human tissue and bone is on its way. The man researching it, Professor Saso Ivanovski, explains what this development really means for the future of dentistry. John Burfitt, reports.

Griffith University’s Professor Saso Ivanovski is, quite clearly, in two minds about the dental industry’s reaction to his research. The news in recent months about his ground-breaking work, using a 3D bioprinter to grow missing bone and tissue from a patient’s own cells, has caused ripples across the profession.

In one respect, Prof Ivanovski is delighted with the positive response he has received to his innovative research project, which he has dubbed the ‘Holy Grail’. It is what he has been working towards since he was a PhD student at the University of Queensland 20 years ago.

Yet, in spite of the attention, there is also a reluctance to use the term ‘revolution’—though the project’s promise undoubtedly suggests that in the long run.

Instead, the cool-headed Prof Ivanovski opts for something of an understatement, describing his pioneering process as, “very, very exciting technology.”

These are exciting days for Prof Ivanovski—and game changing for dentistry. The professor and his team at the Gold Coast’s Menzies Health Institute Queensland have achieved a breakthrough  in creating a process that will print individual bone and gum implants that can be placed into a patient’s jaw. The work is indeed both a personal goal and an industry revolution.

“It was conceptually always a Holy Grail that we’ve been aiming for, but the advances in this area have really been extraordinary and it’s been fantastic to see it actually happen,” Prof Ivanovski admits.

“What was essentially science fiction only 10–15 years ago is now becoming close to reality. We can now actually implant these structures into patients—it is just extraordinary.”

This work is a true labour of love for the professor. But it is the pay-off for the patient that is obviously paramount. “Certainly, the regeneration of lost structures is a little bit of a Holy Grail. The ability to do that will have a huge impact for a large number of patients—there is little doubt about that.”

A step into the future

This major step into a brave new world of dentistry is one that could well change the way, not only that periodontal procedures are conducted, but also that a clinic operates in the treatment of patients. Yet, the professor admits that he is not so comfortable with such dramatic descriptors as the term ‘revolutionary’.

While thrilled by the excitement, he has to keep reminding people that there is still a great deal of work to be done before the procedure manuals and clinic equipment can be rewritten and overhauled—even if that is only a matter of years away.

“As with any new technology, I think we need to temper our enthusiasm, although we do have a significant amount of preliminary data, and we’ll be moving into clinical trials for some of the more straightforward techniques and applications that we want to do with this technology, probably within the next 12 –24 months,” he says.

“It’s going to take time for this to be more widely integrated into practice and also for our surgical techniques and all the practical aspects to catch up with the technology. It’s the same with dental implants. They were invented 50 years ago, yet it’s probably only been in the past 10–15 years that they’ve become a regular part of general practice.”

The new technology will be a significant improvement on traditional methods where bone and tissue are taken from other parts of the body—like the hip or skull. Instead, the bioprinter will be able to produce bespoke gum and bone segments in one single process.

The procedure will operate initially with a CT scan of the damaged jaw area. The scan of this region will then be sent to the 3D bioprinter to design and manufacture a replacement part.

Set at the correct physiological temperature in order to avoid destroying cells and proteins, the bioprinter will be able—in one single process—to fabricate gum structures (bone, ligament and tooth cementum) that have been lost to disease.

The cells, the extracellular matrix and other components that make up bone and gum tissue can be manufactured to exactly fit the missing bone and gum for each particular individual.

The study has so far focused on utilising autogenous cells—a patient’s own cells—in the replication process.

“The 3D printer allows for a very good control of tissue in engineered constructs both at the macro level, in fitting the structure of a particular patient, and also at a nano and micro level as well, so the precise architecture of the tissue is replicated,” Prof Ivanovski explains.

“The unique thing about the bioprinter is that it allows us to print cells and other structures such as growth factors at physiological temperatures. The cells stay alive during the process so, when they’re delivered into the 3D printed structure, you have viable cells that can grow, replicate and contribute to the regenerated tissue, both before and after insertion into the body.”

Once implanted, the manufactured structure will be absorbed into the body and should eventually be indistinguishable from a person’s own native tissues.

The possibilities are limitless

Griffith University’s study, in collaboration with the Queensland University of Technology and University of Adelaide, has so far focused on two main areas where this new technology can best be put to use. One is in the treatment of gum disease; the other is preparing bones in the mouth for implants.

Prof Ivanovski explains that the new technology will make dealing with both conditions a much simpler process for dentist and patient.

“With gum disease, the current techniques are focused on stopping it from getting worse. We can’t regenerate the usually substantial amount of gum tissues, ligament and bone that’s been lost,” he says. “So there is a great advantage with the potential in this development to improve the outcomes of periodontal regeneration treatment. When people have lost teeth, there is often not enough bone for implants to be placed. The 3D printing of bone tissue will mean that it can integrate into the patient and provide the necessary foundations for implants.”

Other plans for the future involve trials with allogenic cells—from the same species but different individuals. Prof Ivanovski says that what they have achieved in trials so far has been encouraging—the new host seems not to reject the cells. This has taken him one step closer to his ultimate goal:

“Eventually, we would like to have an off-the-shelf product, where people can just grab a structure and then, using a bioprinter, create new material for that patient that can be inserted.”

He also looks forward to the day when a 3D printer is in every dental clinic, so that material can be produced while the patient is in the chair, and then directly inserted.

“That is probably the ultimate end point to our research, but the testing and trials with real patients are beginning now,” he explains.

“What was essentially science fiction only 10–15 years ago is now becoming close to reality. . .it is just extraordinary.” – Professor Saso Ivanovski

The question of how to safeguard patients, so the process avoids complications, is a guiding factor as the trial moves into its next phase. It is something that Prof Ivanovski admits plays a strong role in influencing their directions.

“We’re putting bioactive materials into a person and we have to show very clearly that we can control that process, and we do have strategies around managing that.

“We’re working on strategies where we can get the bioactivity without necessarily implanting the cellular structures and putting the patient at additional risk. So we continue thinking about, not just the science, but the ways in which it can be practically integrated.”

It was while Prof Ivanovski was still a student at UQ, studying dentistry, that the seeds for this innovation were born. After completing his initial studies, a young Ivanovski was about to embark on his PhD and was discussing with his supervisor and mentor, Professor Mark Bartold, what areas he wanted to explore.

“This work is exactly what we spoke about,” he recalls. “It was something we saw huge potential in and I hoped to be able to bring it to the clinic one day. Prior to that conversation, I didn’t really see it at all on the horizon, and now this is where it has all ended up.”

Though he knows he is facing many more months of study ahead, in both the lab and the clinic, Prof Ivanovski admits that, with the pace technology is moving, the integration of these new processes will only be a matter of time.

“These days, we’re far more used to the utilisation of new technologies being accelerated,” he suggests. ”So it may be very exciting to see where we are five years down the road. I think that, within five years, a lot of these will certainly be utilised reasonably widely—especially in specialist centres, if not yet in the everyday dental practice.

“Ultimately, of course, the end point is very clear—it is to the clinic, the clinical application and bringing it to as many patients and practitioners as possible. But it’s taken a long time to get to this point, and there is still a huge amount of work to be done.”

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