1st March 2022 - Richard Whatley, CEO BioMin Technologies Ltd
The fundamental principles of preventive dentistry are the preservation of tooth structure and the repair of lesions to minimise the risk of progression of oral disease. The management of the dynamic equilibrium of demineralisation/remineralisation of tooth enamel is key to this process.
The effect of acidic attack on dental tissue, whether caused by the bacterial conversion of sugars in the case of caries, or by direct dissolution caused by reflux of stomach acids or consumption of acidic foods and drink, needs to be mitigated through the protection of the tooth surfaces, neutralisation of oral fluids, and replacement of lost tooth mineral. It is for these purposes that bioactive glass technology can offer tremendous benefits to preventive dentistry. Oral healthcare and dental materials incorporating bioactive glass technology are set to have a long term future in oral healthcare1.
Bioactive glass technology
Bioactive glasses are derived from the family of calcium phosphosilicate materials that are able to degradein body fluids such as saliva and blood. They can act as a vehicle for delivering ions beneficial for healingand remineralisation. Bioactive glasses were first developed by Professor Hench2 and colleagues at the University of Florida back in 1969 for bone augmentation in orthopaedic surgery. Their use in oral healthcare did not emerge until around the millennium with the introduction of Novamin, which is the active ingredient in GSK’s Sensodyne Repair and Protect; continuing to employ the same glass formulation specifically developed by Prof Hench for bone augmentation.
Whilst reviewing the properties of bioactive glass materials in the early 2000’s, Professor Robert Hill of Queen Mary University, London, UK, realised this original bioactive glass could be optimised specifically for oral healthcare application by:
- including fluoride3,4 within the glass structure to provide controlled, longer term release
- dramatically increasing the phosphate content5
- reducing the particle size.
Over the subsequent decade, Prof Hill together with his co-workers developed fluoro calcium phospho-silicate6,7 bioactive glass compositions (fluoride bioactive glass, commonly referred to as FBAG), which feature in BioMin F toothpaste, and subsequently explored their formulation in dental materials such as remineralising composites, varnishes and cements which are currently in pre-market development.8,9,10
The mode of action of FBAG commences when it becomes in contact with water. The hydrogen ion of water will exchange with the calcium ion of the bioactive glass and increase the pH, hence having a neutralising effect. The glass chemist is able to design the structure of the silicate glass to control the rate of this dissolution. In acidic conditions, where the hydrogen ion concentration is increased, this reaction will proceed more rapidly. This dissolution results in the controlled release of calcium, phosphate and fluoride ions which combine to form fluorapatite and then crystalise on the tooth surface, particularly at nucleation sites such as those found in the peri-tubular tissues of open dentine tubules.
When formulated into toothpastes, FBAG is very effective at occluding these tubules and providing increased resistance to subsequent acidic attack. An adhesive system is included in the toothpaste formulation so that the bioactive glass particles bond to the tooth surface, in a similar manner to glass ionomer cements, allowing the active ingredient to remain in situ for many hours after brushing. The benefits of FBAGs in toothpaste have been validated in recent clinical studies11-16 and also confirmed by many dental clinicians who have prescribed BioMin F to their patients over the past 5 years. In a similar manner, the crystal deposition may also occur on early stage enamel lesions as reported in scientific studies10 and may aid the remineralisation process.
Over the past 60 years, fluoride has become the mainstay of dental public health, incorporated into toothpastes, varnishes and other treatments, even added to the water supply in many regions. Its positive effects in terms of decreasing levels of caries in children, especially in deprived areas, have been clearly shown11. The advent of fluoride treatment has transformed preventive care since its introduction in the late 1940’s17.
Why fluoride is so effective and its mode of action remain a subject of debate18. However, one of its main functions is without question the acceleration of apatite formation, developing the more stable and acid-resistant fluorapatite on tooth surfaces19. Also it is believed that bacteria are less able to adhere to fluorapatite than non-fluoride treated enamel 13. Unfortunately, concerns have been raised regarding fluoride’s potential toxicity however, these are often made without taking into consideration the relatively low concentration applied using a toothbrush.
The debate on fluoride concentration continues further with many clinicians believing the more that is applied, the greater the preventive effect. This is not necessarily true as indicated in the 1990’s by Prof Ten Cate20 who stated that ‘For treatments to be effective longer than the brushing and salivary clearance, fluoride needs to be deposited and slowly released.’ This was further supported by research by Mohammed N.R21 et al looking at the effect of various fluoride ion concentrations on demineralised enamel by 19F MAS-NMR. This research showed that at and below 45 ppm [F-] in solution, fluoride-substituted apatite formationpredominates, and above 45 ppm, calcium fluoride formed in increasing proportions. Further increases in fluoride concentration caused no further reduction in demineralization, but increased the proportion of calcium fluoride formed.
There are references in the dental literature claiming calcium fluoride to be reservoir which will release free fluoride16. However, because of its very high insolubility in water (0.015 g/L @18 °C), which only slightly increases under acidic conditions, this theory seems very unlikely. Hence, the remineralising effect of fluoride is optimised at relatively low concentration. The precise level is yet to be precisely determined, however Prof Hill believes this probably lies between 10ppm and 45ppm. This has also been demonstrated by Farooq et al when comparing the remineralisation effects of FBAG toothpaste with a standard 1450ppm sodium fluoride toothpaste. They showed that the FBAG toothpaste provided increased surface micro-hardness, reduced surface roughness and greater volume gain22.
Sodium fluoride is regularly included in standard fluoride toothpastes, although there are other fluoride salts which are also often utilised. In all cases, the fluoride salts are soluble in water and hence the fluoride concentration will exponentially diminish in the mouth through salivary dilution after brushing, and even more rapidly if the patient rinses the mouth immediately afterwards.
The half-life of fluoride concentration in the mouth at normal salivary levels is in the order of 5 minutes and so the length of time that the fluoride concentration remains in the optimal 10-45ppm range will be relatively short. Because of the controlled and sustained manner of fluoride release from the FBAG toothpaste over time, it is possible to provide high level protection using much lower levels of fluoride than featured in standard soluble fluoride toothpastes. This new material may offer a viable alternative for the more efficient delivery of fluoride than that from a traditional soluble fluoride toothpaste.
Resin Restorative Materials
Most experts agree that the life expectancy of a posterior composite resin restoration is between 5 and 7 years. This relatively short duration is largely due to shrinkage on setting, resulting in marginal gaps that lead to leakage and secondary caries23. This longevity is inadequate if we are to move away from the use of amalgam which lasts at least double that period. By including FBAGs into dental composite formulations, substituting a high percentage of their inert glass content, researchers have shown it is possible to produce a composite resin capable not only of filling a cavity but also of re-mineralizing the area around hard carious lesions following minimally invasive removal19.
The inclusion of bioactive glass in dental composites is believed to inhibit bacterial decay and promotes remineralisation24. Prof Kuzic of Oregon State University states: ‘The bacteria in the mouth which cause cavities don’t seem to like this type of glass and are less likely to colonise on fillings which incorporate it’. They are also believed to reduce enzyme-mediated degradation and promote the remineralisation of demineralised dentine25.
The inclusion of FBAGs into dental composite materials creates an apatite-like phase in the marginal gap providing a marginal seal, preventing acid attack by raising the local pH, and reducing the likelihood of failure of the composite. Therefore, bioactive dental composites may improve the longevity and clinical outcomes of composite restorations18. In future, it is also possible to include additional ions into the FBAG such as zinc and magnesium to develop further properties to the restorative material22.
The future looks bright for the application of FBAG within a wide variety of oral healthcare and dental materials. Its use is likely to become a standard tool for the dental clinician to develop a more preventive approach to patient care and improved quality of life.
- Goldstep F. Proactive intervention dentistry: a model for oral care through life. Compend Contin Educ Dent Suppl 2012;33(6):394–6, 8–402
- Hench LL. The story of Bioglass . J Mater Sci – Mater Med 2006;17:967–78.
- Brauer D.S., Karpukhina N., O’Donnell M., Law R.V. and Hill R.G. “Fluoride containing bioactive glasses: Effect of glass design and structure on degradation, pH and apatite formation in simulated body fluid” Acta Biomaterialia 6 (2010) 3275-82
- Mneimne M., Hill R.G., Bushby A.J. and Brauer D.S. “High phosphate content significantly increases apatite formation of fluoride-containing bioactive glasses”. Acta Biomater. 7 (2011) 1827-34
- O’Donnell M.D., Watts S.J., Hill R.G. and Law R.V. “The effect of phosphate content on the bioactivity of phosphosilicate glasses” J. Mater. Sci. Mater in Med. 20 (2009) 1611-8.
- Al-eesa N.A., Johal A., Hill R.G. and Wong F.S.L. Fluoride Containing Bioactive Glass Composite For Orthodontic Adhesives” Dental Materials 33 (2017) 1324-9
- A. Al-eesaa, A. Johal, R.G. Hill, F.S.L. Wong Fluoride containing bioactive glass composite for orthodontic adhesives — Apatite formation properties Dental Materials 34 (2018) 1127-33
- Novel fluoride and strontium-containing bioactive glasses for dental varnishes-design and bioactivity in Tris buffer solution Thaer JaberAl-Khafaji Ferranti Wong Padhraig S.Fleming Natalia KarpukhinaRobert Hill JNCS 503-504 120-130 (2019)
- A.Al-eesa, N.Karpukhina , R.G.Hill , A.Johal, F.S.L.Wong Bioactive glass composite for orthodontic adhesives – formation and characterisation of apatites using MAS-NMR and SEM Dent.Mat.35 597-605 (2019)
- A. Al-eesa, S. Diniz Fernandes, R.G. Hill, F.S.L. Wong, U. Jargalsaikhan, S. Shahid Remineralising fluorine containing bioactive glass composites Dental Materials (2021) 37 672-681.
- Gautam V and Halwai HK Comparison of Clinical Efficacy Of Four Dentifrices In the Management Of Dentinal Hypersensitivity.International Journal of Scientific Research 6 m(2017) 239-240.
- Ashwini S, Swatika, K, Kamala DN Comparative Evaluation of Desensitizing Efficacy of Dentifrice Containing 5% Fluoro Calcium Phosphosilicate versus 5% Calcium Sodium Phosphosilicate: A Randomized Controlled Clinical Trial Contemp Clin Dent 2018;9:330‑
- Vishanth S, Sherwood A, Guttman JLMurugadoss V and Prince E. Evaluation of 3 different treatment modalities for conservative management of attrited, sensitive molar teeth – A preliminary 12-week report Aust Endod J ? (2020) 1-9
- Hussain H Jan SM Behal R Clinical comparison of 5%Fluoro Calcium Phosphosilicateversus 5% Calcium Phosphosilicate in the Treatment of Dentine Hypersensitivity. International Journal of Medical and Biomedical Studies 3 (2019) 146-50
- Patel VR Shettar L Thakur S, Gillam D, Kamala DN. A randomised clinical trial on the efficacy of 5% fluorocalcium phosphosilicate-containing novel bioactive glass toothpaste J. Oral Rehab. 46 (2019)1121–1126
- Naumova EA, Staiger M , Kouji O, Modric J, Pierchalla T, Rybka M, Hill RG and Arnold WH “Randomized investigation of the bioavailability of fluoride in saliva after administration of sodium fluoride, amine fluoride and fluoride containing bioactive glass dentifrices” BMC Oral Health (2019) 19:119
- Robinson C. Kirkham C and Shore S. Dental Enamel Formation to Destruction CRC Press (1995)
- Christoffersen J, Christoffersen MR, KibalczycW, Perdok WG: Kinetics of dissolution and growth of calcium fluoride and effects ofphosphate. Acta Odontol Scand 1988; 46: 325–336
- Featherstone JDB, Shields CP, Khademazad B, Oldershaw MD: Acid reactivity of carbonated apatites with strontium and fluoride substitutions. J Dent Res 1983; 62: 1049–1053.
- Ten Cate J. Contemporary perspective on the use of fluoride products in caries prevention Br Dent J214 (2013) 161–167.
- Mohammed, N. R., Kent N.W., Lynch R.M.J., Karpukhina N., Hill R., and Anderson P.. "Effects of Fluoride on in vitro Enamel Demineralization Analyzed by 19F MAS-NMR." Caries Research 47, no. 5 (2013): 421-428.
- Ali S, FarooqI, Al-ThobityAM Ahmad M, Al-KhalifaS AlhooshanI and Sauro S. An in-vitro evaluation of fluoride content and enamel remineralization potential of two toothpastes containing different bioactive glasses Bio-Medical Materials and Engineering, 30, (2019 )487-96
- Melissa Tiskaya, Saroash Shahid, David Gillam, Robert Hill The Use of Bioactive Glass (BAG) in Dental Composites: a critical review Dental Materials. (2021) 37 296-310.
- Khvostenko, TJ, Hilton JL, Ferracane JC, Mitchell JJ. Kruzic Bioactive glass fillers reduce bacterial penetration into marginal gaps for composite restorations. Dental Materials 31 2015 701-10.
- Tezvergil-Mutluay, R. Seseogullari-Dirihan1, V.P. Feitosa, G. Cama, D.S. Brauer, and S. Sauro Effects of Composites Containing Bioactive Glasses on Demineralized Dentin Journal of Dental Research 96 (2017) 999–1005.