Publishable summary

The Biodensol project proposes three PhD studies to address the problems of (i) Caries and (ii) enamel erosion by acidic foods (leading to sensitive teeth). In both cases, encouraging re-mineralisation (the formation of new calcium phosphate) can help avoid these problems. Where restorative work is required, re-mineralisation has potential to enhance the lifetime of restorations and so further reduce the number of visits to dentists. The PhD studies will represent a big challenge to the Early Stage Researchers (ESRs) selected, since knowledge of both materials chemistry and biology (cell testing for cytotoxicity and bioactivity) will be required. This knowledge resides at Lucideon and University of Lyon respectively and the students will spend 3 cycles of 6 months at each organisation to allow for iterations.

Whilst the powder materials being developed by each student are versatile and could be used in a number of bone / tooth scenarios, each student has an end-goal product in mind. The picture below shows in yellow the areas within a tooth structure where their product will best be used. The orange area represents a restoration.

Biodensol Image

The 3 target composite products, each featuring novel powder developed, are:

-   Product 1) An improved bonding layer product to strengthen and retain “restoration to tooth” interaction (benefit: longer duration restoration

-   Product 2) An improved glass ionomer cement restoration

-   Product 3) A restoration material for deep dentine repair, where apatite growth via cells on the pulp-side is stimulated.

To date, the ESRs have focussed largely on development and characterisation of novel inorganic powder materials. Two students are exploring different sol-gel routes for powder production and one is working on melted glass formulations. Key characterisation techniques are XRD, XRF, SEM, ICP, zeta potential, FTIR, Surface Area / Porosity. All students have been encouraged to make use of Factorial Experimental Design to accelerate their efforts to generate promising powders.

At the University of Lyon, the main work has been focussed on the performance assessment of the developed powders (both mechanically and biologically). Specific formulations (for example as part of a novel glass-ionomer cement restoration) have been evaluated. The following characterizations have been performed:

-             DSC/TGA: To find the polymer decomposition and crystallization temperature (thermal behaviour, type of kinetics and mass lost timing).

-             XRD: to analyses the phase of the samples

-             BET/BJH: to analyze the surface area, pore volume and pore size

-             ICP: to study ion release profile at different time points

-             FTIR: to study different chemical bonds in the glass

-             TEM: to determine the pore features

-             Optical microscopy analysis and SEM: to study the particle morphology and apatite (structural characterizations).

In addition, the influence of the elaborated biomaterials on our cell culture model has been tested; human pulpal fibroblasts were cultured in direct contact with a biomaterial used as reference. The metabolic activity of cells has been then analysed with the Alamar Blue® assay.

Significant progress has been made on sol-gel development for product 1. The desired sol-gel powders need to be amorphous and have low solubility (but high porosity) to both stimulate re-mineralisation and allow adsorption (then release) of anti-bacterial or re-mineralisation agents. This has been delivered for high Ca / low Na formulations in Si-P-Ca-Na systems, following extensive studies into the role of chemistry and sintering conditions

For product 2, glass compositions within a B-Al-Ca oxide triaxial have been melt-quenched (left-hand photos in figure below) and then subsequently heat-treated (right-hand photos in figure below) to cause phase separation. Regions of high phase separation have been identified and analysis carried out to understand the chemistry and rate of ion leaching from the chemically weaker phase. Preferred compositions are being identified with a view to achieving both initial ion release (to set ionomer cements) AND latter ion release to stimulate re-mineralisation once the composite restoration weakens.

Biodensol Image2

Project 3 has proved more challenging. The aim here is to make porous soluble P-Ca-Na sol-gels whereby dissolved ions stimulate a cellular response.  Additional use of Sr to assist cellular response is also being investigated. Many proposed sol-gel routes employ toxic raw materials and / or have led to problems with unwanted crystallisation, carbon entrapment and loss of porosity. Some fused glass equivalent powder have been made and will be evaluated in cell tests first. Further attempts will be made to generate porous sol-gel equivalents in year 3.

Aside from project 3, where extra sol-gel investigations are needed, the second half of the project will see less effort on powder development and more on evaluating the powders (a) for cytotoxicity, bioactivity and then (b) for mechanical and ageing properties in the final composite product.  Projects 1 and 2 are on track to deliver prototype composite materials for evaluation.

Project website : www.biodensol.eu

Coordinator: Professor Brigitte Grosgogeat, Université Claude Bernard Lyon 1 (brigitte.grosgogeat@univ-lyon1.fr)

Industrial Partner: Philip Jackson, Lucideon (Phil.Jackson@lucideon.com)