Smiles Better

The search continues for new and improved materials and treatments in dentistry, reports Katrina Megget

They might not seem it, but teeth are really complex organs, even though we only use them for eating and smiling,’ says Paul Sharpe, Head of the centre for craniofacial and regenerative biology at King’s College London.

The enamel coating our teeth is the hardest substance in nature. Yet, not with-standing the introduction of fluoride in the middle of last century, teeth are subject to fractures or disease. An estimated 3.5bn people around the world suffer from caries and gum disease (periodontitis), while the average number of fillings per person is estimated at seven. With no cure for these diseases, dentistry focuses primarily on restoration – essentially using materials such as silica, composite resins, polymers, metals and porcelain to restore the function, integrity and morphology, explains David Watts, Professor of biomaterials science at the University of Manchester, UK.

Introduced more than 150 years ago, dental amalgam was widely used until a few decades ago when concerns arose over possible environmental and health effects related to mercury. Since then, Norway and Sweden have both introduced legislation banning amalgam, while the World Health Organization (WHO) has recommended a global phase-out.

‘The retreat from using amalgam has motivated the emergence of dental composite restoratives as the most common standard of care,’ says Watts. These composite resins, also known as white fillings, are generally a mixture of powdered glass and plastic resin, which are cured with light and resemble the appearance of natural teeth, making them the preferred cosmetic choice by consumers. These fillings also have robust mechanical properties and bond strongly to enamel, Watts says.

That said, these fillings aren’t perfect. As Watts explains, toxins can potentially leach from the filling, shrinkage can occur during photocuring, which can lead to restoration failure and vulnerability to recurrent tooth decay, and they only have a short shelf life before needing to be replaced. This has spurred incremental improvements and alternative approaches with varying degrees of success, Watts notes. For instance, photocuring of composites has become more rapid, reduced from 60 seconds down to as little as three in some cases, and there have been attempts, largely unsuccessful, to develop self-adhesive composite resins to reduce the need for bonding agents.

But what is really needed are materials comparable to natural teeth in strength and appearance, and which can bond with the different dental tissues, are biocompatible and can easily be manipulated, he says. ‘The key factor in clinical success remains operator skill, but this is facilitated by materials with greater user-friendliness and abuse tolerance. Promising ideas demand first, a clear understanding of dental tissues, the oral environment, and the real-world constraints upon materials – [specifically] mechanical properties, chemical stability and biological safety.’

Aided by scientific, technological and digital advances that have converged with dentistry, research in the search for better materials has boomed. ‘Global materials innovation for dentistry is a thriving, ongoing reality,’ says Watts.

This is evidenced by the hive of activity at the Oregon Health and Science University (OHSU) dentistry school in the US. For one team, the goal is to increase the longevity of fillings so they don’t ever have to be replaced. ‘Today’s dental restorations typically only last seven to ten years before they fail. They crack under the pressure of chewing, or have gaps form between the filling and the tooth, which allow bacteria to seep in and a new cavity to form,’ says Carmem Pfeifer, Associate Professor of restorative dentistry at OHSU. ‘Stronger dental materials mean patients won’t have to get fillings repaired or replaced nearly as often. This not only saves them money and hassle but also prevents more serious problems and more extensive treatment.’

The team created a methacrylate-based resin filling material mixing in the additive thiourethane, which is found in the protective coating of car bumpers and wooden decks. The study, which evaluated the impact on mechanical properties, showed that composites filled with thiourethane-silanised inorganic fillers showed up to 35% lower stress, compared with the unsilanised filler and methacrylate-silanised controls while doubling mechanical properties values.

‘When thiourethanes are added into the methacrylate matrix, the improvement of the mechanical properties is attributed to the flexible nature of the covalent bonds formed between the thiol on the thiourethane with the methacrylate via chain-transfer reactions, leading to a more uniform and tougher network,’ Pfeifer explains. ‘In the present study, those flexible bonds were formed around filler particles, a region where stress concentration occurs.’

The team believes the new material might also reduce the formation of gaps between the material and tooth, which would reduce bacterial colonisation and restoration failure due to secondary decay. Further studies are testing this hypothesis.

Composite resin fillings that display bacterial inhibitory activity have the potential to substantially hinder the development of this widespread oral disease.
Lihi Adler-Abramovich laboratory of bioinspired materials and nanotechnology, Tel Aviv University, Israel

Antibacterial fillings

Secondary tooth decay and dental restoration failure affects an estimated 100m patients/year. New antibacterial dental materials could cut that figure by disrupting the adherence of bacteria to the tooth and reducing biofilm formation. ‘When bacteria accumulate on the tooth surface [and reside in the restoration-tooth interface], they ultimately dissolve the hard tissues of the teeth [causing cavities],’ says Lihi Adler-Abramovich, Head of the laboratory of bioinspired materials and nanotechnology at Israel’s Tel Aviv University. ‘Composite resin fillings that display bacterial inhibitory activity have the potential to substantially hinder the development of this widespread oral disease.’

To develop such a material, Adler-Abramovich’s team discovered potent antibacterial activity of the fluorinated fluorene amino acid compound fluorenylmethyloxycarbonyl (Fmoc)-pentafluoro-L-phenylalanine, which is a self-assembling peptide. The team then incorporated nano-assemblies of the antibacterial within dental composite restoratives and evaluated the antibacterial capabilities, finding that the upgraded material hindered bacterial growth and viability on the dental material and were not toxic. Nor did the new modification affect the mechanical or optical properties of the material.

‘The minimal nature of the antibacterial building block, along with its high purity, low cost, ease of embedment within resin-based materials and biocompatibility, allows for the easy scale-up of this approach toward the development of clinically available enhanced antibacterial resin composite restoratives,’ says Adler-Abramovich.

The Tel Aviv University research is an example of the rapid advancement of peptide and amino-acid-based nanotechnology applied to biomedical materials, but is also an example of a wider nanotechnology trend specifically in dental materials. The approach aims to use nanotechnology to improve the properties of existing materials. Besides composite resins, the technology has also been applied to resin modified glass ionomers, which act as a dental sealant.

Another trend, notes Watts, is the shift towards developing a material with potential bioactivity; that is, a material that has a biological effect on the surrounding tissue. The interest goes beyond current treatments of simply patching the damaged tooth, and instead, a bioactive material, for instance, could stimulate the production of dentin, so it can repair itself, or strengthen the tooth by releasing fluoride or other ions. Bioactive glass was developed in the late 1960s and has been found to promote remineralisation and bonding between dental tissue and restorative material, as well as antibacterial and desensitising properties. It already features as an active ingredient in Sensodyne Repair and Protect toothpaste but there is much potential for its use in restorative material and in coating implants, where further research is needed.

Regenerative dentistry

Bioactive materials are just a step away from regenerative dentistry, which is an attractive alternative to restorative material because the diseased tissue is replaced with natural tissue, forming an integral part of the tooth. ‘Regeneration is addressed with increasing success in the context of periodontal cavities to promote bone re-growth,’ says Watts. ‘This often involves scaffold materials wherein bone cells may grow and proliferate.’

This concept was applied, for instance, by a team at Katholieke Universiteit (KU) Leuven in Belgium. They used 3D printing technology to print scaffolds made of chitosan, a sugar found in the exoskeleton of crabs, fungi and insects. Using chitosan from an animal and fungal source, the scaffolds were investigated for their application in the regeneration of immature teeth to control infections and induce dentine and root formation. The researchers found there was enhanced bioactivity through the formation of an apatite layer – the foundation for enamel and dentine formation – and improved human dental pulp stem cell attachment and viability. The researchers believe there is now scope to modify the scaffolds with the addition of bioactive glass to help promote bone regeneration.

Various research has looked at the regenerative capacities of synthetic materials, growth factors, cytokines, biological extracellular matrices and combinations of these. But a cell-based approach is becoming more favoured in line with advances in cellular and molecular biology. ‘Few if any current dental treatments are based on tissue biology or directed towards tissue regeneration,’ says Sharpe. Yet teeth and their support tissues are an ‘easily accessible treasure chest of stem cell populations’, such as dental pulp-derived cells, that could be exploited to enable a new era of dental treatments, he says. ‘I see no reason why dentistry should not embrace these advances and begin a major drive to move beyond the continuing introduction of yet more non-biological materials-based incremental “improvements” in treatments.’

The holy grail, of course, would be the formation of a replacement biological tooth, Sharpe says. ‘Current implants are metal implants screwed into the jawbone then capped with ceramic or plastic to look like a tooth. The biotooth concept is to have a cell-based implant, not a metal-based implant, that will grow into a tooth in situ in the mouth.’

Sharpe’s team has already established a proof-of-concept using two cell populations: an embryonic stem cell population and an adult stem cell population. In the lab, they manipulated the cells and grew them into the early beginnings of a tooth. These they transplanted into the mouth of an adult animal, where the teeth continued to grow. ‘This clearly works. The cells did exactly what they would have done if they were sitting in an embryo,’ Sharpe says.

This initial research was published in 2004 but has since stalled because of the need to use embryonic cells, where ethical concerns have imposed limitations on their use in human clinical trials. ‘What remains is to generate bioteeth entirely from adult cells, something that has not yet been shown to be possible. The biggest hurdle then is to identify ways of imparting tooth embryonic-like properties to adult cells that could be easily isolated from patients.’ Sharpe is already looking at molecules and genes with the potential to be manipulated.

‘The science is actually the simple part. The bigger challenge is securing enough money to fund these researchers for the next few years so we can advance the field and get us closer to human applications,’ says Peter Cheung, President of US non-profit organisation Further Health, which focuses on advancing biomedical research and is supporting Sharpe’s biotooth. Over the next few years, Further Health aims to spread awareness and galvanise support so the research is at the point where it can enter human trials. ‘The impact of this technology would be immense,’ Cheung says.

While a biotooth might still be some way off, the scene is set for new discoveries and innovative dental solutions. The application of new technologies such as 3D printing, software-based manufacturing, nanotechnology, molecular biology and biomimetic science has the potential to improve the performance of future materials and treatments, tapping into chemistry, engineering and biology.

Already we can envisage a future that features graphene, tissue engineering, gene-mediated therapeutics that prevent decay, oral biosensors, and even personalised dentistry that could identify optimum filling materials based on interactions with the patient’s teeth and oral microbiome. Now that’s something to smile about.