Title: Optimisation and commercial manufacture of tooth-coloured composite dental-fillings with added poly-antimicrobial (PAM) and remineralising calcium phosphate (CaP).
Funder: Department of Health and Social Care

Abstract: Our aim is to develop a novel dental composite material that will allow more of the natural tooth structure to be preserved and promote repair of the carious tooth tissue. Unlike current dental composite fillings, it will swell to compensate polymerisation shrinkage, promote antibacterial action and tooth remineralisation and bond to dentine without additional adhesive. This will be achieved though combined use of a Polymeric AntiMicrobial food preservative (PAM) and remineralising reactive Calcium Phosphate (CaP) particles currently employed in bone cements. Use of monomers and fillers from current dental adhesives and composites respectively will also enable high monomer conversion to improve wear resistance and human cell compatibility. The formulations must also pass ISO tests for ease of CE marking. Workpackages to be undertaken: 1) Stable pastes with rheological properties suitable for easy clinical placement will be formulated 2) Subsequent rate and level of light activated cure and shrinkage will be assessed. Both in-house spectroscopic and ISO tests will be employed. 3) Volumetric expansion will be determined via mass and density measurements. Expansion is caused by CaP/ PAM enhancing water sorption. It should be comparable with polymerisation shrinkage and not reduce colour stability. Maximum levels of CaP and PAM that can be added will be elucidated. Figure 4 provides example preliminary data, expected property values, ISO (4049, 10993) limits, data for commercial comparison and indications of feasible relative component levels. Factors controlling release rates of PAM (eg sample dimensions, PAM concentration, surrounding fluid composition) will also be quantified (see for example Figure 3d) and compared with theory to enable prediction of in vivo behaviour. 4) The relative ratios of CaP and PAM that optimise precipitation of surrounding calcium phosphate mineral will be found. Methods in Figure 3a, 3b, 4e, 4f will be employed in addition to assessment of changes in volume (ISO 17304), in water versus simulated body fluids (SBF, ISO 23317). These studies will provide an indication of the depth of dentine that could be remineralised and how much affected dentine a clinician could leave to self-repair. 5) Bonding to dentine as a function of CaP and PAM level will be quantified (ISO 11405). This will be strongly affected by changes in dentine composition such as mineral and water content. These effects will be assessed by controlled water sorption and de-mineralisation of dentine prior to use. Other properties such as strength and wear resistance (ISO 4049 and 14569) must additionally be comparable or better than for current composites. 6) Relative growth of human cells versus bacteria in extracts and on the surfaces of set materials will be assessed. Furthermore an in vitro test that quantifies bacterial growth under a cavity will be developed (eg Leung et al. methods). This would help in material optimisation and help advise on future treatment strategies (eg levels of infected dentine removal). 7) Key properties of an optimised material manufactured externally will be compared with those of the same formulation produced in &ndash; house. 8) Long term optimised formulation stability and mechanical properties will be assessed. 9) A technical file will be produced to enable CE marking. Milestones at the following months will be: Phase 1 1) (18 months) &ndash; A material that passes standard tests with several unique selling points will have been optimised 2) (24 months) &ndash; Equivalence of externally and internally produced materials will be demonstrated. Phase 2 3) (30 months) &ndash; Long term formulation stability will have been proven 4) (36 months) &ndash; A CE marked product with an extensive technical file that provides evidence of benefits will be ready for clinical trials.

Lay abstract: Dental decay is caused by bacteria. The bacteria use sugar in food to produce acid that makes holes in our teeth. If this decay is not treated the tooth becomes painful and may need to be taken out. A recent NHS study indicated that 28% of five year olds in England have teeth with dental decay and 3% have had extractions as a result (Davies, 2013). Worldwide, this disease affects 60-90% of children and almost 100% of adults (WHO, 2012). Dental fillings are used to replace parts of teeth that are infected. In 2010/11, dental problems in England cost the NHS &pound;3.3 billion (3.1% of its yearly programme budget) (Harker 2012). Most of this money pays for the dentist s time, 60 - 70% of which is spent replacing failed fillings. Silver fillings (amalgam) have been used for a long time but a ban on their use is imminent due to issues over their mercury content. Alternative white fillings (dental composites) are more difficult and therefore expensive to put into the tooth. Furthermore, composites require more frequent replacement than amalgam. The most common reason for replacement is debonding of the composite from the tooth surface allowing continuation of decay. This is a particular concern for children as their tooth decay progresses more rapidly. Our project aim is to optimise new filling materials that are easier to place, require less removal of tooth structure and last much longer. This will be achieved by the addition of low levels of a large polymeric antimicrobial (PAM) that inhibits bacterial cell growth. Furthermore, low levels of calcium phosphate (CaP) are added that with the PAM enable reversal of the damage caused by the bacteria. These materials will be good for treatment of all caries affected patients but are particularly beneficial for children.

Research activity codes: 6.3 MEDICAL DEVICES
Health categories: ORAL AND GASTROINTESTINAL