Where the rubber meets the road

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implant failure
Dr Karan Gulati has found that modifying dental implants with ‘nanopores’ can help protect against one of the leading cuaues of implant failure. Photo: Glenn Hunt

New research by Dr Karan Gulati may lead to a solution to the problem of implant failure. By Rob Johnson

While we’re aware of the risk factors for implant failure, a lot of work has focused on optimising conditions for success in each patient’s mouth. Which, when you think about it, is like solving a problem with a car by fixing the road. Surely it would make more sense to develop a cost-effective way of fixing each individual implant. Dr Karan Gulati, NHMRC Early Career Fellow from the UQ School of Dentistry, may have done just that.

The success rate of implants in healthy patients is between 90 and 95 per cent. “But when we are talking about compromised conditions such as diabetes, osteoporosis, aged patients, or smokers, the success rate drops—for instance with smoking, the success rate can be as low as around 80 per cent,” says Dr Gulati.

The problem is the race to invade. “There is a race to invade between the different cells at the site of implant when we implant anything that is foreign to the human body,” he explains. “The type of cells which adhere and colonise the site of implantation first dictates the success/failure of the implant and the extent of integration.”

The variables that impact on that race include the individual structure of the soft and hard tissue in each mouth. For an implant to work it needs to integrate with that tissue before bacteria attaches and colonises. “The way I put it is, we are looking at the three ‘I’s,” says Dr Gulati. “First one is the integration, both soft and hard tissue. Then comes the immunomodulation, where we modulate the activity of macrophages (the inflammation). Then the third one is controlling the microbes to prevent infection.”

Dr Gulati has just published a proof-of-concept paper that demonstrates a cheap and easy way of modifying the surface of an implant—by adding nanopores and nanotubes—that addresses the three ‘I’s. By ‘cheap’, he means something that can be set up in an average dental surgery and cost <$10 per implant. By ‘easy’, he means a process that takes only 10 minutes. 

Working with the best

If you spend your career studying teeth and the mouth, that’s where you’ll look to address implant failure. It just makes sense. You adjust the mouth to have the best chance of accepting the implant. So it would have probably taken a non-dentist like Dr Gulati to recognise you can adjust the implant to suit the mouth. To concentrate on where the rubber meets the road.

He started his research back in 2010 when doing a master’s thesis at The University of South Australia. “That is the time when I started working with titanium-based implants,” he says. “During my master’s project and my PhD at the University of Adelaide, I was working more towards the orthopaedic implants. Later, after my PhD, I moved to the Queensland to work with Professor Sašo Ivanovski on dental implants, initially at Griffith University and now at the University of Queensland.”

The appeal of working with Professor Ivanovski wasn’t just that he’s a world leader in dental implantology and dental research. “He’s a clinician, so his expertise takes the research to another level, considering he is always after clinical translation of technologies. That is what interested me back in 2015 when I contacted him for the first time, for a job as a postdoctoral researcher.”

The type of cells which come and adhere and colonise the site of implantation first, to some extent governs the success rate of the implant and the extent of integration.

Dr Karan Gulati, NHMRC Early Career Fellow, UQ School of Dentistry

When he joined Professor Ivanovski’s group, they were focusing on creating a surface on an implant that enabled soft tissue integration. “Most research to date and most developments have been in the part of the implant that is inserted in bone, and the lack of osseointegration,” says Dr Gulati. “The one abutment, one-time concept that promotes soft tissue integration is still new and not widely utilised by dental clinicians.”

There has been a fair amount of work aimed at modifying the abutment surface, and there appears to be general acceptance that electrochemical anodization is a superior method to laser-patterning or photolithography. Dr Gulati’s work has looked at what you can do with that anodization process—which involves creating nanotubes and nanopores on the abutment surface. “Electrochemical anodization has been used for decades to make surfaces corrosion-resistant,” he explains. “You immerse the implant and a counter electrode in a suitable electrolyte, and complete the circuit. Under controlled conditions, when you supply voltage, nanostructures will form on the surface of the implant.

“The technology of anodization by which we fabricate nanotubes and nanopores has not been properly extended on to dental implants. It has been shown that the cellular activity increases with nanoscale modification. The nanoscale surfaces enhance cellular activity because the protein adhesion is enhanced on these surfaces. Our technology follows the one abutment, one-time concept. That is, you fit an abutment once, achieve soft tissue integration and avoid disturbing this seal that protects the integrated implant from the microbial rich oral environment. That is why we title our implant as ‘Fit and Forget’.”

Good things in small packages

Clinicians have tried to enhance integration using microrough implant surfaces, which can be combined with different biological enhancements such as hydrophilicity. “Microroughness is still regarded as a gold standard,” he says. “But the conventional nanoengineering approach is to remove any roughness underneath, so the surface is easy to manage and modify. In our approach, we preserve the underlying micro-roughness and superimpose nanotopography, thus getting the ideal combination of micro- and nano-scale features.”

Our fabrication process ensures the underlying surface features are preserved, and further enhanced by coating it with nanopores and nanotubes. “Our nanotubes or nanopores are mechanically robust. And, because they are hollow, they can be loaded with drugs, proteins, or growth factors. In theory, any chemical or biological molecule can be incorporated. We have also developed different ways in which we can control how much of the drug is released. For instance, we can have a very thin coating of a polymer on top of the open tubes. This polymer will be degrading slowly in a physiological environment which will allow the release of the drug from the deep parts of the nanotubes. We can delay the release from a few hours or days, to a few weeks and months. The idea here is that our therapy can be tailored to match individual patient needs.”

Success of the cell

One of the unexpected highlights of his research has been finding that, using this method, cells align and are mechanically stimulated on the nanopores—greatly enhancing integration. “While the nanotopography enhances the bone and soft-tissue functions, it also modulates macrophages such that we receive a tailored immunomodulatory effect as well, because we don’t want too much inflammatory activity, but we also don’t even want too little.”

The alignment of cells on nanopores is the highlight of the study, because he wasn’t expecting any kind of alignment of the cells. So it was a pleasant surprise to discover that this simple technique can stimulate and control the cellular activity. “We started viewing cells from one hour onwards, but the cellular alignment started at 24 hours on these surfaces,” he says. “Therefore, our surface modification will take care of the three ‘I’s: integration of hard and soft-tissue, immunomodulation and infection control via local release of antibiotics.”

If someone wants to start modifying the surfaces using this technique, all they need is around $1000 to complete the entire set-up, including the cost of chemicals and the power supply. The overall procedure is highly optimised such that multiple implants can be modified in a single step. “As compared to other nanoengineering techniques, this one is very cost-effective. The best thing is, because it is already used in other industries, it is very scalable. You can have different set-ups where you can do 100 implants at the same time, and it can also be a very small and localised set-up, say in a dental clinic, where the dentists can do it themselves.”

Dr Gulati believes human trials are close. “We have done the osseointegration analysis in large animal models with osteoporosis, and the results are encouraging. We are now seeking funding to go into the next stage, which is the human trials. Our technologies are converging at a point where a single surface can take care of the three ‘I’s, but further optimisations are still needed. For instance, how much of a particular drug is needed inside different bone microenvironments, and how do we tune that? There are different models we are working on at this stage, but everything is slowly converging at a point where we will be ready for human trials next year.” 

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