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Don Schwass, Faculty of Dentistry: Creating technology to treat tooth decay

This is Case Study Seven for the Research Impacts study.

Dr Don Schwass and Dr Gemma Cotton image
Dr Don Schwass and Dr Gemma Cotton.

Participants interviewed for the case study

Principal investigator

Dr Don Schwass
Senior Lecturer, Dean’s Office (Dentistry), Faculty of Dentistry

Researcher

Dr Gemma Cotton
Postdoctoral Fellow, Sir John Walsh Research Institute, Faculty of Dentistry

Stakeholders

Dr Kevin Sheehy
Commercialisation Manager, MacDiarmid Institute
Former Health Technology Commercialisation Consultant

Dr Alex Tickle
Commercialisation Manager, Otago Innovation Limited, The University of Otago

Dr Gavin Clark
Dean of Enterprise at Massey University Former CEO of Silventum
Former Director of Research & Enterprise at the University of Otago

Summary of the impact

The research of Dr Don Schwass, a dentist, Senior Lecturer and researcher at the University of Otago, focusses on the incorporation of silver nanoparticles into dental materials to confer antimicrobial properties, and the development of novel dental materials for restorative dentistry. These products are to combat the bacterial dental infections of caries (tooth decay), periodontitis (gum disease) and peri-implantitis (infections around dental implants).

In partnership with Dr Carla Meledandri from the Department of Chemistry and Dr Gemma Cotton from the Faculty of Dentistry, this research resulted in the filing of three patent families, one of which was licensed to a multinational dental manufacturing company.

A spinout company (Silventum) has been formed in order to commercialise the research. Through the research process, Dr Gemma Cotton has gained her PhD and became an employee of Silventum, whilst continuing her research career. This has resulted in improved capability of the research team.

Underpinning research

Periodontitis is a bacterial infection of the bone and supporting tissues surrounding the teeth1. It is associated with an inflammatory response to dental plaque at the gum margin, and can ultimately cause a loss of teeth. Increasingly, tooth loss is treated using titanium dental implant screws to which crowns are attached. These implants are expensive and vulnerable to further gum disease such as peri-implant mucositis – an inflammatory reaction in the gum tissue around the implant, or peri-implantitis which affects the supporting bone, causing the loosening of the implant and its eventual failure2. Current treatment strategies for periodontitis and peri-implantitis involve mechanical debridement and antibiotics, which have limited success as they slow the progression of disease, but do not cure it2. Treatment with antibiotics also carries the risk of inducing bacterial antibiotic resistance, making it harder to treat the infection2.

Don’s research interest is in devising novel treatments for dental caries that are less invasive and less destructive of the tooth than traditional methods. Dental caries can occur when bacteria generating acid demineralises tooth enamel and causes cavities. Don’s first interest was to develop a product that would disinfect dentine, the tooth layer beneath enamel, that had been infected by bacteria from caries. Current treatment of caries is to ‘fill’ the cavity with a restoration, but often the decay is not completely eliminated. If the seal around the restoration breaks down the remaining bacteria can cause further caries. Don’s objective was to develop a substance that would completely inactivate any bacteria remaining in the dentine. Ideally, the substance would remain in the dentine and protect it from further bacterial invasion.

In 2010 Don went to a three-day induction course as a new academic staff member at the University of Otago. This course included a ‘speed-collaborating’ exercise, where staff members paired off and had to introduce themselves and discuss their research interests. In this exercise he met Dr Carla Meledandri, a chemist with expertise in nanoparticle research. They realised that Carla’s expertise combined with Don’s interest in solving clinical problems had significant collaboration potential. Don explained to Carla what he wanted from his novel material – an antimicrobial silver formulation that would not stain dental enamel. Carla saw how she could manipulate the silver nanoparticle size to prevent it from staining. They applied for an Otago Innovation Limited Proof-of-Concept grant, and won, which provided the initial funding for this research.

The first product patented was an antimicrobial solution of colloidal silver nanoparticles that look like water. The product did not discolour teeth, which was important for aesthetic reasons. Silver nanoparticles naturally aggregate, so ligands were used to create micellar structures that held the silver nanoparticles apart. There was a lot of in vitro testing and antimicrobial studies, with approximately 200 iterations before the first product was formulated. Don and Carla developed the product further so that it could be forced into tooth dentinal tubules by iontophoresis – by applying a charge to the tooth. A similar approach had been successfully used in the past when applying fluoride to teeth. Through this advance they produced an antimicrobial compound that binds to the tooth and could be forced deep into exposed dentine.

Following the development of the colloidal product they collaborated with Professor Warwick Duncan (Head of the Discipline of Periodontology, at the University of Otago) to make an antimicrobial for use in periodontal treatments. They generated a gel that could be used in the mouth around teeth and gums that would degrade at a rate that is optimal for tissue repair following dental procedures or dental surgery. Professor Duncan used his established model of
periodontitis in sheep, and developed a novel model for peri-implantitis in sheep to test the gel.

The third product made by the researchers was a silver nanoparticle-containing glass ionomer cement with antimicrobial properties for use as a dental filling restorative material.

Funding

  • Proof of Concept grant, Otago Innovation Limited
  • Partners for Innovation grant
  • Otago Innovation research contracts and commercialisation resources (including patent filing, legal, regulatory consultants, and marketing)
  • Otago Innovation Limited’s devolved MBIE PreSeed Accelerator Fund
  • Powerhouse investment leveraging matching Callaghan Innovation repayable loans (MBIE startup funding)
  • University of Otago Research Grants
  • MacDiarmid Institute

Research snapshot

  • Dr Don Schwass and Dr Carla Meledandri have four publications from this work3–6.
  • Three patented technologies have patents filed7–9, two have been filed nationally in multiple jurisdictions (including Europe, the US, Australia and New Zealand). There is one granted US patent for the first technology.
  • The work has been featured in the media, including the Otago Daily Times10, and in an interview with The Science Show on ABC Radio National (Australia)11.

Recognition

  • Dr Carla Meledandri won the 2017 Prime Minister’s MacDiarmid emerging scientist award, based partly on this work.
  • Dr Gemma Cotton is a graduate of the Kiwinet Emerging Innovator Programme and a commercialisation consultant for Momentum (Return on Science).

Details of the impact

Spin-out company

  • In 2014, the spin-out company Silventum was formed, which will commercialise novel nano-chemistry technology developed from this research. It is currently owned by Otago Innovation (58.82 per cent shares) and Powerhouse Ventures (41.18 per cent shares).
  • The creation of Silventum led to the exclusive licensing of the third (restorative material) technology, and a non-exclusive license for the second (gel) technology.
  • Don, Carla and Gemma are founding staff members of Silventum. At its peak, it employed four people (2.0 FTE).

Building capability

  • Dr Gemma Cotton conducted her PhD with the research team exploring the development of silver nanoparticle-based oral materials. Gemma continued working in the team for a year as a Research Fellow, and as Chief Technology Officer at Silventum. She is now a Research Fellow working with Professor Warwick Duncan and Associate Professor Dawn Coates.

Potential impact

  • The ultimate goal of this research was to take the patented restorative product to market. This has been pursued with great effort (see ‘commericalisation’ under ‘pathway to impact’). It is hoped current research on a fourth product – looking at a new dental filling material that is closer to a tooth’s composition – will support this goal.
  • Silventum hopes to gain further investment via Powerhouse Ventures and additional external investors.
  • One of the goals of Silventum is to manufacture their products in Dunedin, which will bring benefit to the local economy, resulting in job creation.
  • There is potential to develop the products in the area of animal health.
  • Whichever product(s) reach the market will change healthcare practice, resulting in greater prevention of bacterial dental infections. Health benefits include improved wellbeing for patients. There will also be economic impact in reducing the cost of treatment.

Pathway to impact

Addressing real-world problems

  • Dr Don Schwass, with 20 year’s clinical experience, is a passionate believer in addressing real- world problems with research. By reverse engineering clinical problems, he has been able to keep a strong applied focus to his product development.
  • Dr Gemma Cotton wanted to conduct research in this area due to her parents’ dental issues; she was able to visualise the impact of the research might have on them.

Gemma Cotton image“I really wanted to solve problems for society. The reason why I joined their team originally was that my parents had dental issues and so I took their problems and put it into what we were trying to address.”

Dr Gemma Cotton – Postdoctoral Fellow, Sir John Walsh Research Institute, Faculty of Dentistry

High quality research

  • Publishing high quality research papers has been a good marketing tool for the patented technology. Additionally, the University of Otago has a great reputation, so industry partners feel they can rely on the quality of the research.

Commercialisation

  • The pathway to patenting, licensing and regulatory approval is complex, and Don and Carla have worked closely with Otago Innovation Limited through this process. Dr Alex Tickle (Commercialisation Manager at Otago Innovation Limited) became involved once the product was patentable and became project manager. They worked on the provisional patent, developing the business plan and finding industry partners and external investors. Don and Carla were involved in developing a regulatory approval pathway for the first product (the colloid) together with a contracted regulatory consultant and later with the licencee.
  • There is a balance between patenting and publication, as information about the technology cannot be in the public arena prior to patenting, and therefore publication plans are often delayed. This means that researchers may need alternative ways to maintain the publishing requirements for their academic job – for Don this meant participating in other research projects whilst the patenting process was taking place.
  • Don’s experience as a clinical dentist were crucial in the initial stages of scoping the products.
  • Don’s contacts as a clinical dentist supported the development of a network for market validation with dental companies.
  • Carla and Don travelled to the United States, Germany and Liechtenstein to have meetings with major dental manufacturing companies interested in investing in their technology. Otago Innovation organised confidentiality agreements in advance. The fact that these companies were prepared to enter into these confidential discussions commends the relevance and novelty of this research and the existing relationships Don had with some of these companies.
  • KiwiNet (an organisation supported by the Ministry of Business, Innovation and Employment, of which Otago Innovation Limited is a member) gave advice and support, and provided additional industry contacts.
  • Dr Gavin Clark, former CEO of Silventum and former Director of Research & Enterprise at the University of Otago, recommends that researchers approach Otago Innovation Limited early in the research process if they believe that they have an invention that may have commercial value.

Gaining regulatory approval

  • Gaining regulatory approval allowing the technology to be used in patients can be challenging. The original product (the colloid) was exclusively licensed to a dental material company, but as it was too novel compared to existing products and classified as a therapeutic product it had a complex regulatory route, which proved a challenge to navigate.
  • The second product (the gel) was also classified as a therapeutic product and faced similar challenges to the first product.
  • Following their experience with the two therapeutic products, Don and Carla realised there might be better opportunities in designing dental materials, which for regulatory purposes are classified as medical devices, and have a quicker and easier regulatory approvals route to market.
  • Once the third product (the restorative material) was created, this led to the formation of the spin-out company Silventum. Silventum obtained the exclusive rights to the restorative material, as well as a non-exclusive license to the gel to avoid any freedom to operate. They worked through regulatory pathways to see if they could get a product including the restorative material technology onto the market, which has not yet been able to occur. Don and Carla were frequently consulted through this process to verify the technical information.

Collaboration

  • The success of this research has been built on the cross-disciplinary collaboration between Don and Carla, and also by bringing in additional experts such as Professor Warwick Duncan.

“ I guess I’ve just been a bit fortunate, because of the way I’ve thought about clinical problems and also landed on very good collaborations, that has just meant that all the stars have lined up nicely.”

Dr Don Schwass – Senior Lecturer, Dean’s Office (Dentistry), Faculty of Dentistry

Dissemination

  • Don presented research ideas at the European Organisation for Caries Research, where it was perceived as being highly novel and relevant.
  • Otago Innovation Limited provided a demonstration video, patent information and the research team’s publications to a wide range of dental companies. The University of Otago’s press release about the exclusive licence of the colloid reached dental journals as far as the East Coast of the United States. This resulted in dentists approaching Otago Innovation to access Don’s invention.

What next?

  • Current research at Silventum is on a fourth product, aiming for a new dental filling material that is closer to a tooth’s composition.

References

  1. Health Navigator New Zealand. Gum disease. 2019.
    https://www.healthnavigator.org.nz/health-a-z/g/gum-disease/
  2. Meledandri C, Schwass D, Cotton G, Duncan W. Antimicrobial gel containing silver nanoparticles. 2019.
    http://appft.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=2Fnetahtml2FPTO2Fsrchnum.html&r=1&f=G&l=50&s1=222019000075922.PGNR.&OS=DN/20190000759&RS=DN/20190000759
  3. Garden AL, Van Der Salm L, Schwass DR, Meledandri CJ. Towards a tunable microemulsion method for nanoparticle synthesis. RSC Advances. 2013;3(7):2192-6.
  4. Garden AL, Scholz K, Schwass DR, Meledandri CJ. Optimized colloidal chemistry for micelle-templated synthesis and assembly of silver nanocomposite materials. Colloids and Surfaces A: Physicochemical and Engineering Aspects. 2014;441:367-77.
  5. Schwass D, Lyons K, Love R, Tompkins G, Meledandri C. Antimicrobial activity of a colloidal AgNP suspension demonstrated in vitro against monoculture biofilms: toward a novel tooth disinfectant for treating dental caries. Advances in dental research. 2018;29(1):117-23.
  6. Schwass DR, Meledandri CJ. Enhanced Penetration of Silver Nanocomposite Assemblies into Dentine Using Iontophoresis: Toward the Treatment of Dental Caries. ChemPlusChem. 2014;79(12):1671-5.
  7. Schwass DR, Meledandri CJ (inventors). Assembly of micelle aggregates of surfactant micelles and silver nanoparticles and use as an antibacterial agent WO2014116121A9. 2014.
  8. Meledandri CJ, Schwass DR, Cotton GC, Dunanc WJ (inventors). Antimicrobial gel containing silver nanoparticles WO2017061878A1. 2017.
  9. Meledandri CJ, Schwass DR (inventors). Assembly of micelle aggregates of surfactant micelles and silver nanoparticles and use as an antibacterial agent. US10064891B2. 2018.
  10. Gibb J. New technology preserves decayed teeth. Otago Daily Times. 2015.
    https://www.odt.co.nz/news/campus/university-of-otago/new-technology-preserves-decayed-teeth
  11. Williams R. Don Schwass. The Science Show. 2013.
    https://www.abc.net.au/radionational/programs/scienceshow/don-schwass/5140684