R&D Department

Biodentine

Active Biosilicate Technology™

Scientific File

Summary
Introduction ................................................................................................................................................................. 4

‚ Active Biosilicate Technology™ ƒ Physico-chemical features

............................................................................................... 5

1.1 - Setting reaction ..................................................................................................................................................... 6 1.2 - Formulation of Biodentine™ ...................................................................................................................... 7
............................................................................................................... 8

2.1 - Setting Time ............................................................................................................................................................. 8 2.2 - Density and Porosity ...................................................................................................................................... 10 2.3 - Compressive strength .................................................................................................................................. 11 2.4 - Flexural strength ................................................................................................................................................ 12 2.5 - Vickers micro hardness ............................................................................................................................... 12 2.6 - Radiopacity ............................................................................................................................................................ 13 2.7 - Comparison with Glass Ionomers and ProRoot® MTA ..................................................... 13

„ Biodentine™ Interfaces

...................................................................................................................... 14 3.1 - Resistance to acid ........................................................................................................................................... 14 3.2 - Resistance to microleakage .................................................................................................................... 16 3.3 - Electron Microscopy ...................................................................................................................................... 18

… Outstanding biocompatibility

.................................................................................................... 20

4.1 - Cytotoxicity tests (ISO 7405, ISO 10993-5) ............................................................................... 20 4.2 - Sensitization tests (ISO 7405, ISO 10993-1) ............................................................................ 21 4.3 - Genotoxicity tests (ISO 7405, ISO 10993-3, OCDE 471) ............................................... 22 4.4 - Cutaneous irritation tests (ISO 7405, ISO 10993-10) ........................................................ 23 4.5 - Eye irritation tests (OCDE 405) ............................................................................................................. 23 4.6 - Acute toxicity tests (ISO 7405, ISO 10993-11, OCDE 423) ......................................... 23 4.7 - Preclinical safety conclusion .................................................................................................................. 23

† Evidence based bioactivity

............................................................................................................ 24 5.1 - In vitro test of direct pulp capping on human extracted teeth .................................. 24 5.2 - In vitro test for angiogenesis .................................................................................................................. 25 5.3 - Stimulation of reactionary dentine in indirect pulp capping : rat model ............................................................................................................................ 25 5.4 - Calcification as a result of Biodentine™ in a direct pulp capping and pulpotomy : pig model ................................................................................... 26 5.5 - Overall bioactivity ............................................................................................................................................. 28

‡ Clinical efficacy

................................................................................................................................................. 29

6.1 - Biodentine™ is used as a dentine substitute under a composite .......................... 29 6.2 - Biodentine™ is used as a direct pulp capping material ................................................. 31 6.3 - Biodentine™ is used as an endodontic repair material .................................................... 32

References

................................................................................................................................................................ 33

3

Introduction
Biodentine™ was developed by Septodont’s Research Group as a new class of dental material which could conciliate high mechanical properties with excellent biocompatibility, as well as a bioactive behavior. Several years of active and collaborative research between Septodont and several universities led to a new calcium-silicate based formulation, which is suitable as a dentine replacement material whenever original dentine is damaged. In addition to the chemical composition based on the Ca3SiO5 – water chemistry which brings the high biocompatibility of already known endodontic repair cements (MTA based), Septodont increased the physico-chemical properties (short setting time, high mechanical strength…) which make Biodentine™ clinically easy to handle and compatible, not only with classical endodontic procedures, but also for restorative clinical cases of dentine replacement. Sealing ability of this biomaterial was also assessed to be equivalent to glass-ionomers, without requiring any specific conditioning of the dentine surface. Leakage resistance and mechanical strength will improve over the first weeks after placement. Biodentine™ turns out to be one of the most biocompatible of all the biomaterials in dentistry as demonstrated according to all the ISO standard tests, as well as in the different preclinical and clinical research collaborations. Moreover, reactionary dentine formation was demonstrated in rats, exhibiting high quality and quantity of protective dentine stimulation in indirect pulp capping. In the case of direct pulp capping and pulpotomy in pigs, the compatibility with the pulp enables a direct contact with fibroblasts, with limited inflammatory response compared to controls. Formation of a regular and dense dentine bridge is histologically demonstrated within one month. Besides the usual endodontic indications of this class of calcium-silicate cements (repair of perforations or resorptions, apexification, root-end filling), Biodentine™ has been evaluated for its restorative properties versus composite (Z100™, 3M ESPE) in a three year follow-up, randomized, multicentre clinical study in 400 patients. It was suitable as a permanent dentine substitute and temporary enamel substitute. Restoration of deep or large crown carious lesions provides a very tight seal, without post-operative sensitivity and insures the longevity of restorations in vital teeth. Biodentine™ has also achieved 100% success in direct pulp capping in adults presenting healthy pulp.

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high mechanical strength and short setting times. This consists in controlling every step of the material formulation beginning with the purity of the raw materials. calcium aluminates (C3A). Grinding Firing Ground powder Biodentine capsule 5 . The only way to reach our objectives in terms of purity control. This implies that all these products inherently contain unpurifiable mixtures of calcium silicates (C3S + C2S). Septodont is now able to ensure the purity of the calcium silicate content of the formulation and the absence of any aluminate and calcium sulfate in the final product. low mechanical properties and with very difficult handling (depending on the water ratio. calcium aluminoferrites (C4AF).‚ Active Biosilicate Technology™ Septodont’s initial objective was to develop a material based on the most biocompatible chemistry available for dental materials: calcium silicates. Although recognized as highly biocompatible and bioactive. which result from the clinker products manufactured by the building industry from natural stone treatment. calcium sulfates (CaSO4 . from a sandy consistency to a fluid paste). Usual dental calcium silicate cements are based on the “Portland Cement” materials. with very long setting times (more than 2 hours). together with low concentrations of metallic impurities coming from the natural minerals used as raw materials. all these materials lack reactivity. In order to take up the technological challenge of combining this calcium silicate chemistry with the requirements of a formulation compatible with classical restorative and endodontic practice. The Active Biosilicate Technology™ is a proprietary technology developed according to our state-of-the-art pharmaceutical background applied to the high temperate ceramic mineral chemistry.gypsum). was to synthesize our own calcium silicate product. Septodont developed a new technological platform called Active Biosilicate Technology™. which can set in the presence of water.

Setting reaction The calcium silicate has the ability to interact with water leading to the setting and hardening of the cement. The C-S-H gel formation is due to the permanent hydration of the tricalcium silicate. This precipitation process is reinforced in systems with low water content. The hydrated calcium silicate gel and the excess of calcium hydroxide tend to precipitate at the surface of the particles and in the pores of the powder.SiO2 = C3S) which produces a hydrated calcium silicate gel (CSH gel) and calcium hydroxide (Ca (OH)2). thereby slowing down the effects of further reactions. The hardening process results from of the formation of crystals that are deposited in a supersaturated solution. 2(3CaO. which gradually fills in the spaces between the tricalcium silicate grains. 2H2SiO4 Ca O2H CSH CaOH 2+ H2 O Biodentine™ Particle The unreacted tricalcium silicate grains are surrounded by layers of calcium silicate hydrated gel. Powder before hydration Deposition of CSH Biodentine™ after setting 6 . which are relatively impermeable to water.2SiO2. due to saturation of the medium.SiO2) + 6H2O  3CaO.3H2O + 3Ca(OH)2 C3S CSH This dissolution process occurs at the surface of each grain of calcium silicate.1.1 . This is a hydration of the tricalcium silicate (3CaO.

Usually calcium silicate cements have setting times in the range of several hours. The paradox of calcium silicate systems is also that water. Increasing the setting time was achieved by a combination of different effects. but on the other hand decreasing the water content leads to reducing the possibility of a homogenous mix. helps in maintaining the balance between low water content and consistency of the mixture. 7 .1. The additional charge system selected was calcium carbonate. which make the product fragile. The second axis of formulation was to adjust the particle size distribution in order to reach an optimal powder density. the shorter the setting. Radiopacity is obtained by adding zirconium oxide to the final product. First. Also. Powder Tri-calcium Silicate (C3S) Di-calcium Silicate (C2S) Calcium Carbonate and Oxide Iron Oxide Zirconium Oxide Main core material Second core material Filler Shade Radiopacifier Liquid Calcium chloride Hydrosoluble polymer Accelerator Water reducing agent Reaching high mechanical strength is also quite difficult for these systems. since the higher the specific surface. excess water in the system will create some remaining porosity. The first cause of low mechanical properties of Portland cements are the aluminate components. adding calcium chloride to the liquid component accelerates the system. particle size greatly influences the setting time. for both its biocompatibility and calcium content. The addition of hydrosoluble polymer systems described as “water reducing agents” or super plasticizers. Septodont controls the purity of the calcium silicate through the Active Biosilicate Technology™ which consists in eliminating aluminates and other impurities.Formulation of Biodentine™ In order to reach a formulation with a short setting time (12 minutes) and high mechanical properties in the range of natural dentine. which is too long in most of the protocols in clinical practice. On the hand. the decrease of the liquid content in the system decreases the setting time to harden within 9 to 12 minutes. Finally. significantly degrading the macroscopic mechanical resistance. calcium silicates could not be used alone.2 . which is essential for the hardening of the product. can also affect the strength of the material.

This instrumented method was used to determine the setting time of the Biodentine™ Formulation (Fig. with a 2 mm gap.1) and to compare it to a classical glass ionomer (Fuji IX – GC) and ProRoot® MTA (Dentsply).5°C. by a viscoelastometry. The time between the mixing and the initial setting corresponds to the working time. Piscataway. The final setting time was determined as the elastic modulus reached 100MPa. and the transmitted stress is proportional to the strain. This system can therefore be used to measure the evolution of the elastic modulus G’ of the material.ƒ Method: Physico-chemical features 2.0015%). The experimental conditions were as follows: oscillation frequency: 1 radian per second. when a sinusoidal strain is applied. This is the principle of the ISO standard 9917. the sample was inserted between the two striated parallel plates. After mixing. The initial setting time was determined at the moment when the elastic modulus begins to increase (10MPa). the applied strain is less than the critical strain beyond which the structure of the cement paste is altered (about 0. Only the lower plate was maintained at the controlled temperature of 37. 6 mm in diameter. and a closed chamber maintained the temperature of the entire sample at 100% relative humidity to prevent drying. without any modification of the structure of the material. An ARES strain-controlled rheometer was used (Rheometric Scientific Inc. it corresponds to the setting time.Setting Time There are several methods to evaluate the setting of dental materials.0005%. Dynamic rheometry tests were performed to determine the characteristics of each material during their workability (working and setting times) as well as the rate of building early mechanical resistance. Under these conditions. The first one is based on the macroscopic evaluation of the resistance of a needle to penetrate the surface of the material: when the needle does not leave a trace on the surface of the material.. the constraint transmitted by the sample. 8 .1 . An alternative instrumented and more objective method can be used especially to help in the selection of different formulations: the use of a rheometer (Nonat and Franquin. US). These tests consisted in measuring. 2006). applied strain: 0.

1(1.12) 3. MTA gun). which set in more than 2 hours. The classical glass ionomer sets faster that Biodentine™ in less than 4 minutes.Fig. This represents a great improvement compared to the other calcium silicate dental materials (ProRoot® MTA). with an amalgam carrier or with carriers which are used for endodontic cements in retrograde fillings (Messing gun.58) 175 (2. The setting times of Biodentine™ are in the same range as the amalgams. the working time is over 1 minute and the setting time is between 9 and 12 minutes. Biodentine™ has a consistency after mixing which enables manipulation with a spatula.20) 6 (0. In all these cases.20) From these results it can be concluded that the working time of Biodentine™ is up to 6 minutes with a final set at around 10-12 minutes. When tested according to the ISO standard with the Gilmore needle.30) 10. the instruments should be rinsed with water just after their use in order to avoid that excess of Biodentine™ will set inside the systems and cause blockage. 9 .4 (0. 1: Dynamic rheometry evaluation of the initial and final setting times.55) 1 (0. Material PMTA FUJI IX BIODENTINE ™ Setting times (Minutes) Initial Final 70 (2.

2 . Two different methods confirmed the low porosity of Biodentine™.002) BIODENTINE ™ 2. Material Dens.002) Porosity % 22.2 (0.002) 0. the material continues to improve in terms of internal structure towards a more dense material.2) 6.2) 7. Micromeritics Instruments Corporation. Fig. Measurements were carried out on fourteen 28-day-old cylinders.120(0. the higher the mechanical strength. USA).Density and Porosity The mechanical resistance of calcium silicate based materials is also dependant on their low level of porosity. Mercury.033(0.320(0. The samples were prepared under the same conditions as those used for CS measurements.882(0.2) As expected. dried at 40°C in a primary vacuum for 12 days to eliminate residual water.002) Porous characteristics Pore V. can be forced into pores. Electrical Resistance Measurements An alternative method to illustrate the hardening process is to examine the mobility of ions which depend of the pore size and number of pores during setting by electrochemical analysis. The lower the porosity. Biodentine™ exhibits lower porosity than ProRoot® MTA. The porous volume and the distribution of pore diameters were determined by mercury intrusion porosimetry (Autopore III.031(0. Biodentine™ is an evolutive material which improves its mechanical properties with time.2) (Golberg et al. Norcross. The density and the porosity of Biodentine™ and Fuji IX are equivalent. the only known liquid really suitable for porosimetry type measurements. with a decrease in porosity. 2009).260(0. The pressure required to intrude mercury into a pore is determined by the pore diameter.2.cm3/g 0. This shows that even after the initial setting of Biodentine™. 2: Electrical resistance (Ω) versus time (hours) during setting of Biodentine™ 10 . First a mercury intrusion porosimetry method was used.002) 0.8 (0. g/cm3 PMTA 1. Impedance spectroscopy technique leads to the increase of the electrical resistance along with the porosity reduction (Fig.6 (0..002) FUJI IX 2. The superior mechanical properties of Biodentine™ were determined by the low water content in the mixing stage.

5 (5. USA). Specimens were stored in an incubator for 15 minutes in 100% relative humidity (dry) with 37°C and then removed from the mould and stored (wet) in distilled water at 37°C.3 .3) a 131. ProRoot® MTA samples were left in the incubator for 24 hours at 37°C and 100% relative humidity (dry) to allow complete hardening.4 (8.3: Comparative evolution of compressive strength after setting of Biodentine™.7)b 253. according to each manufacturer’s instructions.3)c ≤ 0. This value becomes quite stable and is in the range of the compressive strength of natural dentine (297 MPa.001 28d 139.5 (7.1)c ≤ 0.Compressive strength Compressive strength is a classical mechanical evaluation of the dental biomaterials (ISO 9917:1991).9)b 316.6 (16. Minneapolis.1)b 0. for the remaining time (simulation of the clinical application). The setting of Biodentine™ is illustrated by a sharp increase in the compressive strength reaching more than 100 MPa in the first hour.01 24h 7.1)b 241.1 (13. Material PMTA FUJI IX BIODENTINE ™ p value 1h 144. Eden Prairie.001 7d 164. Each product was tested at 1 hour.5 mm by minute and the maximum load was recorded (Fig.2) a 185. 3).2.2 (33.9 (35.7)c ≤ 0. The mechanical strength continues to improve to reach more than 200 MPa at 24h which is more than most glass ionomers values. 6 specimens were prepared using cylindrical Teflon moulds. removing air bubbles. 4 mm in diameter and 6 mm long.001 Compressive strength (Mpa) Time (h) Fig. 11 .2 (16. The cylinders were compressed using a Universal Testing Machine (Model 2/M MTS Systems 1400.5 (19.3 (25. 7 days and 28 days. Fuji IX and ProRoot® MTA. with a cross-head speed of 0.3) a 220. Specimens were mixed at room temperature.2 (6. A specific feature of Biodentine™ is its capacity to continue improving with time over several days until reaching 300 MPa after one month. 1 day.1) a 188.

the mechanical strength develops after several days. 61-182 MPa (composite resin) (O’Brien 2008). Biodentine™ is an evolutive biomaterial which improves its mechanical properties with time. 2.(O’Brien 2008)). The formation of CSH gel reduces the porosity with time. 17-54 MPa (Resin modified GIC). With ProRoot® MTA. the hardness of Biodentine™ was 51 HVN and reached 69 HVN after 1 month.Vickers micro hardness Hardness can be defined as the resistance to the plastic deformation of the surface of a material after indentation or penetration. but still much lower than the composite resin.. No continuous increase over one month can be observed with Fuji IX but Biodentine™ is significantly more resistant to compression. it shows clearly that the bending resistance of Biodentine™ is superior to conventional GIC. very similar to Glass Ionomers (15-39MPa). the compressive strengths are similar. The value of the bending obtained with Biodentine™ after 2 hours is 34 MPa. which was illustrated previously. the lower the risk of fracture in clinical use. The crystallization of the latter continues. II and IV cavities.5 . 2009)). the material has no mechanical resistance. even after 1 day. Comparing the compressive strength of a classical glass ionomer (Fuji IX – GC). 12 .4 . This demonstrates the superiority of Biodentine™ for building in short time (9-12 min) sufficient mechanical resistance to be used as a dentine substitute. These values are comparable to those obtained with the resin modified GIC-Fuji II LC (36 HVN). After 2 hours. The higher the resistance to flexural strength. 2. Biodentine™ has surface hardness in the same range as natural dentine. Compared with that of other materials: 5-25 MPa (conventional Glass Ionomer Cement). Measurements at different times have been evaluated The hardness increases in time when cements are immersed in distilled water (Colon in (Golberg et al. at 1 hour. The reported micro hardness values for natural dentine are in the range of 60-90 HVN (O’Brien 2008). compressive strength…). reaching 150 MPa after one week. The internal values of the flexural strength were 22MPa. As classical Portland cement. Calcite is a mineral known to improve the hardness of cements. compatible with dental restorations.Flexural strength The 3 points bending test has a clinical significance and is essential when the material is used for Class I. and the composite resin-Post Comp II LC (97 HVN). therefore improving the hardness as well as other mechanical properties (sealing at the interfaces. This maturation process can be related to the decrease of porosity with time.

1 (4.6 (4. According to the ISO standard 6876.5) 16.3 (3.8 (1.9) 129.0 (7.2) 24.3) 213.7 (26.0 (2.8) 12.1 (1.Comparison with glass ionomers and ProRoot® MTA In order to have a larger knowledge of the physico-chemical behavior of Biodentine™ compared to glass ionomers and Portland cement based dental materials (ProRoot® MTA.3) 22.8) 39. Biodentine™ displays a radiopacity equivalent to 3.6) 915325 16.1) 60.3) 162. flexural strength.11.7) 22.7 (1.5) 14.7 .Radiopacity Biodentine™ contains zirconium oxide allowing identification on radiographs.3) 22.0) 76.4 (1.5) 10.2) 6.5 (0. Dentsply). 0(1.4) 8.6 (10.2 (3.5 mm of aluminum.4 (14.8 (4.9) 32.8) 130.1 (0.9) 70.2) 19.6 (2.4) 15. This value is over the minimum requirement of the ISO standard (3 mm aluminum).5 Biodentine™ 3M Glass Ionomer VOCO Ionofil® Molar AC GC Fuji IX GP Capsule GC Fuji IX GP (hand mix) GC Fuji II Light Cure Capsule GC Fuji II Light Cure (hand mix) ProRoot® MTA 16. The mechanical resistance of Biodentine™ is also much higher than that of ProRoot® MTA.8 (10.6 .5) 9. 13 .9 (5.6 (3.3 (6. it can be concluded that Biodentine™ has a mechanical behavior similar to glass ionomers and is also similar to natural dentine. 2.5 (2.3 (4. we performed several measurements in Septodont’s laboratory: diametral tensile strength (DTS).8 (3.3 (0.1) 45.09 349270 - - 18.0 (7.4) 183.8) 43.4 (3.5) 14.1) 124.3) 77.5 (1.0) 27.2) Non measurable Non measurable 56.08 167-B-19.5 (2. This makes Biodentine™ particularly suitable in the endodontic indications of canal repair.1) 72.01.9 (2.7 (10.5 mm/min 297 60 Product Lot # DTS.0) 26.9 (17.8 (2. compressive strength at 24h. elastic modulus. Vickers microhardness. MPa Flexural Strength MPa Modulus GPa Natural Dentine Dental Materials & their selection (O’Brien 2008) 193-A-03. Compressive Strength at Microhardness 24h(MPa) HVN 0.1 (7.8 (1.9) 902101 0811141/ 0811031 812111 0902231/ 0812081 08003394/ 08084 16.2) Non measurable From this table.2.7) 38.1 (5.5) 122.

74). in the oral cavity. will differentiate its interfacial behaviour from the already known dental materials (composites. the dissolution/precipitation process. diameter 30mm) for a week.4). Aging was evaluated in Meyer-modified Fusayama artificial saliva containing phosphates (pH 5. Scanning electron microscopy was used to examine and characterise the surface of the sample before and after Aging.Resistance to acid Concerning durability of water based cements. Ca. Zr. It is known that glass ionomers have a tendency to erode under such conditions.3). The acid erosion and the effects of aging in artificial saliva on the Biodentine™ structure and composition were investigated (Laurent et al. In the case of Biodentine™. Methods: The acid erosion test was evaluated daily in lactic acid (0. This was investigated by erosion in acid solutions. 14 . The possible dissolution of the new material in the artificial saliva was evaluated by measuring the concentration of Si. 2001). The height modification of the material was evaluated for a week. and inorganic carbonate in the artificial saliva after 1.1M) aqueous solution (pH 2. but this erosion is slower than with glass ionomer cement reported by Nomoto (Nomoto and McCabe. adhesives. glass ionomers). 3. enamel. one of relevant characteristics of the dental materials is the resistance to acidic environment. 3 and 4 weeks. 2.74 pH solution.02M) and sodium lactate (0. which is inherent to the setting principle of Calcium silicate cements.1 . acid erosion is observed (Fig. by measuring the height loss of the Biodentine™ samples (2mm.„ Biodentine™ Interfaces The quality and durability of the interface is a key factor for the survival of a restoration material in clinical conditions: the marginal adaptation and the intimate contact with the surrounding materials (dentine. electron microscopy and microleakage tests. Results : In the 2.. 2008). composites and other dental materials) are determinative features.

Scanning electron microscopic analysis of this material revealed needle-like crystals with an apatitic appearance. a crystal deposition on the surface of Biodentine™ occurs. 500 400 Depth (µm) 300 200 100 0 50 100 time (h) Fig. In reconstituted saliva (containing phosphates). This correlates well with the analysis of the elements in the solution. 15 .In artificial saliva there was no erosion but deposition of white material on the surface of the Biodentine™ sample. with an apatite-like structure. no erosion is observed.74. The composition of this deposit by X-diffraction analysis seems to confirm the apatitic composition (ratio Ca/P = 1.3) As a conclusion. This deposition process due to a phosphate rich environment is very encouraging in terms of improvement of the interface between Biodentine™ and natural dentine. the erosion of Biodentine™ in acidic solution is limited and lower than for other water based cements (Glass Ionomers). which revealed a decrease of Ca concentration with time. Instead. This type of crystal deposition is already well known for MTA systems.4: Acid erosion profile in pH=2. The deposition of apatitic structures might increase the marginal sealing of the material.6). which in turn. lactic acid/lactate solution Biodentine Ketac Fil Fuji II 150 200 Apatite-like crystal deposition on the surface of Biodentine™ in a phosphate containing artificial saliva solution (pH=5. corresponds to the precipitation of apatite-like calcium phosphate crystals.

) before Biodentine™ placement. The interface with dentine and enamel was examined using dye penetration methodology (silver nitrate).. •At the enamel . Dentsply or G Bond.2 . Dentsply) over Biodentine™ one day after setting. At 3 months no significant differences at the composite-Biodentine™ interface were observed between Xeno® III or G Bond and Xeno® III + Optiguard®. Methods: Freshly extracted human molars were used to prepare class II cavities both on the mesial and on the distal sides. no significant difference could be evidenced in the case of Optiguard® placement or not. the interfacial seal. The prepared teeth were divided into different groups to evaluate the influence of a pretreatment of the cavity using polyacrylic acid solution (GC Conditioner. 10 seconds for each batch and transfer). After 3 months.Resistance to microleakage: Several studies were performed to evaluate the resistance of Biodentine™ to microleakage. The percentage of microleakage was determined on six samples as the length of dye penetration divided by the length of the interface. the micro leakages of specimens treated with G Bond were lower than at 1 day. the application of a surface varnish (Optiguard®.3. The placement of a protective varnish increases microleakage at the enamel interface in the early stage. which is one of the most commonly used assays to assess.BIODENTINE™ interface: % Dye Penetration = (CC1/CD) * 100% • At the composite . After 3 months of aging. but not at the dentine interface. Kerr) after the Biodentine™ setting to protect from humidity after initial setting and the influence of the bonding agent (Xeno® III. the specimens bonded with Xeno® III exhibited significantly less microleakage than those bonded with G Bond. 16 . At the Biodentine™-composite interface (Fig. GC Corp. in vitro.BIODENTINE™ interface: % Dye penetration = (AA1/AB) * 100% • At the dentin . 1 day after placement. Each group was submitted to 2200 thermocycles (5°C – 55°C.5). GC) when placing a composite (Ceram-X® Mono.BIODENTINE™ interface: % Dye Penetration = (EE1/EF) * 100% Results: No significant difference in the percentage of microleakage was observed at the enamelBiodentine™ and dentine-Biodentine™ interfaces. by measuring the percolation of a dye along the different interfaces studied (Golberg et al. 2009). with or without polyacrylic acid treatment.

with or without pre-treatment by polyacrylic acid solutions. are very resistant to micro leakage. Mesio-occlusal and disto-occlusal preparations below cementum-enamel junction were made in 42 extracted molars. the interfaces which are developed between Biodentine™ and the dental surfaces (enamel and dentine) as well as with adhesive systems (Xeno® III or G Bond). Dejou evaluated the micro leakage resistance of Biodentine™ in comparison with one of the best sealing systems. 2 mm 6 mm 2 mm Fig. 5 mm Concerning the first two groups: leakage was evaluated separately. GC Corp. The teeth were randomly assigned one of the following treatments before restoration with Filtek™ Z250 (3M ESPE) composite resin: Biodentine™.Fig. Biodentine™ + Septobond SE (Septodont) .): after 2500 thermo cycles. The sealing quality of Biodentine™ is not influenced by the storage after 3 months.6: Micro leakage scores of Biodentine™ or Fuji IILC in contact with enamel or dentine 17 . resin modified glass ionomers (Fuji II LC. Biodentine™ + Optibond® Solo Plus (Kerr).6). Biodentine™ exhibits better leakage resistance both to enamel and to dentine compared to Fuji II LC. The choice of water based adhesive systems might be preferable when placing a composite over Biodentine™. Fuji II LC (GC) + Optibond® Solo Plus (Kerr). Biodentine™ + Optibond® Solo Plus (Kerr) + silane. Fuji II LC (GC). in contact with enamel or in contact with dentine (Fig. 5: Histogram of mean microleakage % at the Biodentine™ / adhesive interface According to this study. the dye penetration was evaluated by scoring the depth of penetration of silver nitrate marker (ranging from 0= no penetration to 3= full interface penetration) (Internal report).

Pr Dejou.7: Micro leakage scores of Biodentine™ or Fuji IILC in sandwich technique In conclusion. Dr Raskin There is a direct contact without a gap between Biodentine™ and the natural dentine. Fig.3 .7). 3. The crack is observed inside Biodentine caused by dehydration. due to SEM sample preparation under vacuum. The surface of Biodentine™ presents some crystal deposition which appeared after the sample cutting due to re-exposition to water environment. Dr Pradelle 18 . Only in the case of Septobond SE (self etch bonding).Z 250 6 Optibond Solo+ Biodentine FujillLC In the sandwich technique groups. Biodentine™ is then indicated in opensandwich class II restoration without any preliminary treatment.Electron Microscopy: Interface between Biodentine™ (left) and human dentine (right): the two surfaces are in direct and intimate contact. Pr Colon. in case of Optibond® Solo plus (total etch system). at the interface between the base material (Biodentine™ or Fuji II LC) and the composite. Biodentine™ has a similar behavior in terms of leakage resistance as Fuji II LC at the interface with enamel. was the percolation at the interface slightly increased. which indicates the quality of the micro-mechanical adhesion. with dentine and with dentine bonding agents. but no significant difference could be evidenced on the maximal median scores. similar micro leakage resistance are obtained (Fig. This cohesive failure does not affect the dentineBiodentine™ interface.

in an in vitro test of apexification. The dentine tubules are obturated by recrystallisation. Dr Raskin Perfect seal of Biodentine™ in contact with radicular dentine. Dr Franquin Comparison of the interface between Biodentine™ or Fuji II LC and a composite. Pr Dejou. using Optibond® Solo Plus: The interfaces are very similar. Pr Colon. as well as between two increments of Biodentine™. observed after 28 days of storage in distilled water. some mineral re-crystallisation occurs. Dr Bronnec. This process will continue with time. improving the sealing. creating mineral tags. This induces micromechanical anchorage of Biodentine™. Dr Pradelle Crystallisation process in the dentine tubule of an extracted wisdom tooth treated with Biodentine™.At the entrance of the dentine tubules. Pr Colon 19 .

1 . Results showed the expression of the differentiation markers. according to the ISO classification. Cell death after Dycal®. In certain indications (radicular. Dentsply and ProRoot® MTA Dentsply). the cell differentiation was evaluated with the expression of collagen. for long-term tissue contact (>30 days). The following sections evaluate the compliance with this standard for the tests carried out on Biodentine™. calcium hydroxide and MTA (Dycal®. 2003b). MTA (4 weeks) 20 . Moreover. The cell viability was determined by MTT incorporation (About. dentine sialoprotein (DSP) and osteonectin (OSN). Results showed Biodentine™ was non cytotoxic like MTA. Product Biodentine™ MTA CaOH Cell death (%) 0±8 0±9 22±10 Table 1. The biocompatibility tests required for the preclinical evaluation of dental products followed the guideline ISO 7405 .… Outstanding biocompatibility From a regulatory point of view. Expression of collagen and dentine sialoprotein (DSP) after contact with Biodentine™ and MTA during 4 weeks. apical obstruction and repair of the pulpal floor). The first study was performed on human pulpal fibroblasts (human wisdom tooth). It is considered a device with external contact. 1). whereas the undiluted cement Dycal® induced 22 % of cytotoxicity (Table. MTA and BIODENTINE™ contact. 4. ISO 10993-5) Different cytotoxicity tests carried out on Biodentine™ are reported.2008. involving external contact for a period of more than 30 days.Cytotoxicity tests (ISO 7405. All biocompatibility tests were carried out on the final product Biodentine™. used for crown and root dentine repair treatment. underlining the safety of Biodentine™ (Fig. Biodentine™ is a calcium silicate based material. it can be considered an implanted system. comparing Biodentine™. 8). Collagen Control DSP Biodentine™ (4 weeks) Figure 8.

Immunological marking was in all cases higher in the cells forming mineral nodules. ISO 10993-1) Studies were performed on guinea-pigs thanks to a maximisation method (intradermic and topical application with Freund complete adjuvant induction. Samples were extracted 3 h. The sensitisation potential is graded (class 0 to 4) according to the percentage of sensitised animals (score of more than 2). To conclude. marker expression was important in the pulp cells involving the formation of mineral nodules. Biodentine™ was not sensitizing (Gomond. 24 h and 7 days after the setting. The evaluation of oedema and erythema was performed according to a clinical scale (0-4) 24 and 48 h after retrieval of occlusive patches of the challenge phase. They were compared to those induced by the materials used for pulp capping such as MTA and Dycal®. Pulp fibroblasts secrete a mineralised matrix and cells in contact express differentiation proteins (nestin and dentine sialoproteins).. composite resin Filtek™ Z250 and MTA (Franquin. 2008).Sensitization tests (ISO 7405. Results showed Biodentine™ is not cytotoxic (< 10 %) whatever hardening time is considered. The cell viability was determined by MTT incorporation. 2003c). 2001).2 . Once the cells had been in contact with Biodentine™ cement or with MTA. Cell death after Filtek™ Z250. Product Filtek™ Z250 MTA Biodentine™ 3 hours 23% 0% 2% 1 day 25% 14% 10% 7 days 26% 8% 9% Table 2. 21 . 4. • Where there is no dentine interposition. MTA and Biodentine™ contact. dental specialised pulp cells and that moreover it does not affect phenotypic pulp expression of fibroblasts. • Differentiation of pulp fibroblasts in orthodontoblastic cells was also analysed for contact with two materials. these various tests demonstrate that there is no direct cytotoxic effect with Biodentine™ in the form of an extract in contact with L929 fibroblast line cells. Several tests were carried out: • A cytotoxicity test involving indirect contact through a section of dentine: none of the tested materials was cytotoxic.The second study was performed on L929 fibroblasts comparing Biodentine™. The third study was published in Dental Materials on the biological effects of Biodentine™ (Laurent et al. Filtek™ Z250 resin is slightly cytotoxic (> 20 %) at the 3 observation periods (Table 2). there is a significant difference in toxicity of the different materials: Biodentine™ did not reveal any cytotoxicity although more marked cytotoxicity was reported for Dycal® compared to MTA.

AMES test performed on Salmonella typhimurium and Escherichia coli. 1000 bi-nucleated lymphocytes were tested.88 14. An in vitro micronucleus test was also carried out using human lymphocytes (Laurent et al.59 for a dilution of 0. TA1535. Biodentine™ dilution 0.control + control Micronucleoted lymphocytes (%±SD) 4. the slides were analysed by fluorescent microscopy (magnification 400) and an automated analyser was used to determine DNA lesions. A toxicity index was determined.1 4. at 50 mg/ml for 24 hours and at 37°C. In the presence of DMSO.0±6. TA98. OCDE 471) Several genotoxicity tests were performed on the Biodentine™ cement. The results showed that after incubation of the lymphocytes with different dilutions of the extract of Biodentine™. TA100 and TA102. Strains TA98. Identical results were reported for the four strains of bacteria tested (Laurent et al.0* Table 3. The results obtained showed that the percentage of tail DNA varied from 12.0±1. After a culture time of 72 hours.45* Finally.90±1.52±1. TA1537.2 3.1%) when concentrations of 1% to 5% in an aqueous or hydrophobic medium were tested. 2) Biodentine™ 1% 2. to check for a micronucleus.96 46.0±1.3 .96 13.08 13. the number of lymphocytes presenting a micronucleus was similar to that obtained with the negative reference (3. Following electrophoresis.4.3% 3. Another AMES test was performed on 4 strains of Salmonella typhimurium TA97A.0±1.52 for the positive control (Table 3).19±0. pKM101 in absence or presence of metabolism activator.1% to 15.2 4. 2003a). Tail DNA mean after contact with Biodentine™. Results showed that Biodentine™ was not mutagenic (Harmand. These were exposed to extracts of Biodentine™ obtained either from a culture medium or DMSO.1 4... Table 4.31±0.2 16.06 15.58 for the undiluted medium. 2003).59±0.9% to 4. the cells were stained and analysed. The extract of Biodentine™ was prepared in DMSO and a culture medium.Genotoxicity tests (ISO 7405.19 for the negative control and 46. It was 13. together with a ratio for the number of micronuclei in relation to the negative reference. 22 . 2008).7±1.7% 5% .58±1. The cells were exposed directly to increasing dilutions of cement extracts for two hours. ISO 10993-3. Positive controls produced a micronucleus rate of 16% (Fig. 2008). TA100.2±1. The results showed that cement Biodentine™ does not induce reverse mutation in the presence or absence of the metabolic activator S9.1% 1% 10% Undiluted Negative control Positive control Tail DNA mean (%±SD) 12. They were carried out on extracts of the cement after complete setting. Dilutions of 1% to 5% of the extracts were used. the comet test on human pulp fibroblasts was conducted (About. there was no significant difference between the genotoxicity of Biodentine™ and the negative control (extracted with NaCl and DMSO). Micronucleated lymphocytes after contact with Biodentine™ .

Cutaneous irritation tests (ISO 7405.5 . ISO 10993-11.Acute toxicity tests (ISO 7405.4. In conclusion. irritant or sensitising agent.Preclinical safety conclusion The tests carried out on Biodentine™ have shown that the material tested in the form of an extract in a saline environment is not a cytotoxic. 24h. 3h.6 . The liquid part of Biodentine™ undiluted was unclassified among the chemicals irritating to eyes (Fagette. 2003a).4 . 2003b). Biodentine™ is safe. The DL50 of Biodentine™ is superior to 2000 mg/kg (Gomond. ISO 10993-10) Cutaneous irritation test was performed in the rabbit by direct application. Biodentine™ was shown to be non irritant (Gomond. The aim of the study was to assess qualitatively and quantitatively irritation or corrosion and the delay of appearance of the effects after single application of 0. It is devoid of oral toxicity at a dose of 2000 mg/kg. mutagenic. Biodentine™ demonstrates at least equivalent biocompatibility. when compared to ProRoot® MTA. 4.Eye irritation tests (OCDE 405) The irritation of the liquid part of Biodentine™ was tested on rabbit eye mucosa. Rats were observed immediately after administration. OCDE 423) The acute toxicity tests were performed in order to determine on a qualitative and quantitative basis the toxicity signs and their time of appearance after a unique oral administration of a dose of 2000 mg/kg of the product in rats. 48h and 72h after patch removal. 1h. Oedema and erythmea were evaluated 1h. iris and cornea lesions) were scored 1h. 48h and 72h after application.1 ml on eye in 3 rabbits. The ocular reactions (redness and chemosis of conjunctivae. 2h. 4. 4. The administration by oral route of the 2000 mg/kg dose of Biodentine™ induced no acute toxicity in the rat. 2009). 23 . and at least once a day during 14 days. 4h. Compared to well known dental materials such as Dycal® (calcium hydroxide).7 . Biodentine™ exhibits less cytotoxicity. 24h. Moreover.

1 . 2007). Exposed pulp cavities (A) obturated with Biodentine™ (B) and cultured (C). To conclude. Figure 10. with the neo-formation of reparatory dentine comparable to that observed with MTA (Fig 10).† Evidence based bioactivity Two in vitro tests and two tests in animals were performed in order to demonstrate the bioactivity of Biodentine™ in clinical situations. The teeth (n = 15) were cultured for 24 hours (n = 5). At the end of the culture and after demineralisation. Biodentine™ is able to stimulate initiation and development of mineralization. Near the capped area. 14 days (n = 5) and 28 days (n = 5) in order to determine the bioactivity of Biodentine™ (Fig 9). histological sections were done. A B C Figure 9. 5. The results showed good preservation of the pulp up to 28 days. 24 . Observations after 28 days. a change in the pulp tissue was reported. This corresponds to the first signs of the formation of a dentine bridge.In vitro test of direct pulp capping on human extracted teeth Human teeth were extracted in order to make exposed pulp cavities which were then filled with Biodentine™ (About.

Only ProRot® MTA and Biodentine™ were able to stimulate the formation of mineralisation spots. The teeth were collected and fixed at 8 days. 2009).3 . pulp inflammation was moderate in the mesial third of the pulp chamber. 15 days. Moreover. PDGF-AB. VEGF and FGF-2 were enhanced in presence of Biodentine™ (150 à 200% for VEGF and up to 670 % for FGF-2).Stimulation of reactionary dentine in indirect pulp capping : rat model A study was conducted on the maxillary molars of adult rats (Golberg.2 . FGF-2. 11.In vitro test for angiogenesis A study was conducted on damaged pulp fibroblasts in order to evaluate the Biodentine™ activity on angiogenesis (About. The concentration level of TGF-β1 was enhanced by both ProRoot® MTA and Biodentine™. ProRoot® MTA and Xeno®III were applied to the cells and growth factors (VEGF. Hydroxide de calcium XR. The cavities were filled with Biodentine™ and with Fuji IX glass ionomer cement and covered with a protective varnish. This reaction was also observed on the reference teeth (Fig. TGF-β1) concentrations were evaluated by ELISA test. 2009). 25 . Biodentine™ stimulates reactionary dentine (rd). in order to heal pulp fibroblasts. Materials such as Biodentine™. 30 days and 3 months after filling.5. The first maxillary molars were prepared in order to achieve half-moon cavities (class V) on the mesial face. Calcipulpe®. This model mimicked the in vivo situations in cases of pulp damage requiring direct pulp capping. The results showed that after 8 days. 5. These results suggest that Biodentine™ is able to stimulate angiogenesis. Figure. 11). Results showed that none of the products modified the cell structure in this model.

promoted beneficial calcification after one week. 26 . 12. only partially covering the mesial cervical area of the pulp (Golberg. 2009). like White MTA.Calcification as a result of Biodentine™ in a direct pulp capping and pulpotomy : pig model Two protocols were set up in pigs (Shayegan A. Fig.4 . The reactionary dentine formation stabilises at 3 months. Histological sections of the teeth were done after a week. Pulp chamber was excised in 15 pigs in a comparative study of the efficacy of Biodentine™ versus formocresol and MTA (5 pigs per group). The results showed that Biodentine™. a month and 3 months of treatment. 5. After 3 months. The first protocol was the analysis of the pulp reaction following pulpotomy and placement of different materials (15 deciduous teeth. 2009). Biodentine™ was able to stimulate a reactionary dentine which is a natural barrier against bacterial invasions. reactionary dentine generated by Biodentine™ was thick and dense (Fig. whereas Formocresol induced necrosis and inflammation (Fig. 15 pigs): • Formocresol • White MTA • Biodentine™ The follow-up was performed during 1. the formation of reactionary dentine was greater in the teeth in the presence of Biodentine™ and its thickness increased over time from 20 to 40 µm after 8 days. By comparison with the group treated with the glass ionomer cement. 4 and 12 weeks. 12). Formation of a thick reactionary dentine in presence of to Biodentine™ in comparison to Fuji IX To conclude. this was less dense. although it varied between 10 and 20 µm for the reference group. indicating that the stimulation process is stopped when a sufficient dentine barrier is formed. 13).The inflammatory process had disappeared after 15 days. enclosing the horn and the mesial pulp whilst for Fuji IX. 40 to 80 µm after 15 days and 140 to 280 µm after 30 days. The newly formed reactionary dentine was identified.

To conclude. Biodentine™ is a suitable material for pulpotomy. The second protocol was an analysis of the pulp reaction after direct capping for different materials (15 deciduous teeth.Formocresol WMTA Biodentine™ 1 week Inflammation 10/10 Necrosis and inflamation 6/10 Beginning of calcification 10/10 Calcification 4 weeks InflammationTissu regeneration transition 4/10 Necrosis and inflamation 7/10 Important calcification 5/10 Infiltration of inflammatory cells 7/10 Important calcification 12 weeks Complete healing 7/10 Necrosis and inflamation 1/10 Calcification 10/10 Complete calcification 9/10 Complete calcification Fig. Calcium hydroxyde WMTA Biodentine™ 1 week Inflammation 2/10 Calcification 4 weeks InflammationTissu regeneration transition 7/10 Calcification 10/10 Important calcification 10/10 Important calcification 9/10 Calcification 10/10 Important calcification 9/10 Important calcification 7/10 Important calcification 5/10 Partial calcification 10/10 Important calcification 12 weeks Complete healing Fig.14. 15 pigs): • Ca (OH)2 • White MTA • Biodentine™ The follow-up was performed during 1. 13. in order to compare the efficacy of Biodentine™ against calcium hydroxide and MTA (5 pigs in each group) over 3 trial periods of 1 week. 1 month and 3 months (Shayegan 2009). 4 and 12 weeks. Pulp exposure was performed via a class V vestibular cavity in 15 pigs who were 4 months old. Summary of direct pulp capping results. Summary of pulpotomy results. 27 .

These phenomena illustrate the great potential for Biodentine™ to be in contact to the pulp. the quality of the dentine bridge formed with Biodentine™ is of better quality than with the reference dental technique (calcium hydroxide). 28 . generating a reactionary dentine as well as a dense dentine bridge. by demonstrating its bioactivity in several indications. In the first month. Moreover. Biodentine™ is bioactive. 5.5 . As a conclusion.Overall bioactivity Pulp capping and pulpotomy studies showed that Biodentine™ was very well tolerated. Biodentine™ was able to promote mineralisation.To conclude. The performance of Biodentine™ is at least equivalent to White MTA. Biodentine™ enhances the formation of a dentine barrier after direct pulp capping confirming it has good potential in this indication.

due to a low compressive strength incompatible with restorative indications. especially in terms of setting time and compressive strength. Biodentine™ can be defined as a special micronised concrete derived from the main component of Portland cement.Biodentine™ is used as a dentine substitute under a composite A clinical investigation. which is used for dental restorations and requires an adhesive for the bonding the composite on the tooth. This product exclusively composed of mineral components. 24 and 36 months.‡ Clinical efficacy 6. Biodentine™ is applied directly to contact with the tooth. with the same chemical properties. randomised. 12. 6. • Very good marginal adaption. is a derivative of Portland cement. tricalcium silicate. which required the inclusion of 400 patients and a 3-year observation period. • Very good interproximal contact. It was developed as a product for radicular repair only. The interim report is based on 232 cases with a minimum one year follow-up: 116 were treated with Biodentine™ and 116 with Filtek™ Z100. The biological properties of this product allow its use in the capping of dental pulp tissue. 20 involved a direct pulp capping. sold by Dentsply under the brand name ProRoot® MTA. it exhibits the same characteristics of biocompatibility and sealing ability. aimed to assess the acceptability of Biodentine™ as a new restoration of the posterior teeth: a first-in-man study. was initially designed to replace dentine in restorations. MTA. This product. in the filling of the radicular apical part by a retrograde approach or in the closure of perforations. In this study. Biodentine™ is compared to Filtek™ Z100.1 . The study planed a follow-up at baseline. one product shares similar properties with Biodentine™. with controlled (size and spatial organisation) formation of calcium salts. Among the products already used in dentistry. Biodentine™ showed: • Easy handling. prospective study. The analysis of the cases showed: At D0. 29 . Among the 116 restorations done with Biodentine™. This clinical investigation is a multicentre. • Excellent anatomic form. after setting in an alkaline pH. 15 days. without adhesive or conditioner. Mineral Trioxide Aggregate. to promote the restoration of the original tissue in contact with the pulp tissue and radicular tissue. 04/001. With physical properties far superior to those of MTA.

the marginal adaptation and the interproximal contact started to degrade after 6 months.Restoration with Biodentine™ (Courtesy of Prof. • The anatomic form. 30 . 15. In 93. cases needed a retreatment (92/116). Thanks to its excellent biocompatibility. The tolerance was evaluated for up to 3 years. a complementary treatment was performed.During the follow-up. • Due to the degradation. as the same number of adverse events was observed in Biodentine™ group (4/116) as in Filtek™ Z100 group (3/116). Biodentine™ was applied in 116 patients with at least one year follow-up. Biodentine™ was kept as dentine substitute as the pulp vitality test was positive. Biodentine™ presented a good resistance to burring and the composite Filtek™ Z100 was applied on the top. KOUBI. As a conclusion.8%. D0 : Patient restoration D0 : Amalgam removal D0 : Biodentine™ application 6 months later 16 months: Biodentine™ reshaping 30 months later: Biodentine™ under Filtek™ Z100 Fig. the restoration with Biodentine™ in comparison to Filtek™ Z100: • Was well tolerated in all cases. • Was safe for the patient. Biodentine™ is very well tolerated and can be used as cavity lining with a permanent composite restoration (Fig. Marseille).15).

Direct pulp capping with Biodentine™ (Courtesy of Prof. 31 .Biodentine™ is used as a direct pulp capping material In the same clinical trial. Biodentine™ showed: • An excellent tolerance. 16. 04/001.6.2 . 16). Marseille). KOUBI. D0 : Radiography D0 : Exposed pulp D0 : Biodentine™ application D0 Three years later: Biodentine™ covered by Filtek™ Z100. Biodentine™ can be used in direct pulp capping indications with a good success rate (Fig. Biodentine™ was also used as direct pulp capping material. Moreover. Fig. It is important to underline that Biodentine™ was used in contact with pulp tissue in a patient older than 21 and maintained the pulp alive. • The ability to save pulp vitality even in difficult cases: the vitality test was positive at each recall.

Biodentine™ has some features which are superior to MTA. As the setting is faster. there is a lower risk of bacterial contamination than with MTA. ProRoot® MTA). Several physical. aimed at assessing the tolerance and efficacy of Biodentine™ in 6 endodontic procedures. Adding to its ability to be used as dentine substitute. after 3 months and after 2 years follow-up is in progress: • Direct pulp capping following carious pulp exposure • Direct pulp capping following dental trauma/injury to healthy pulp (partial pulpotomy) • Repair of perforated root canals and/or pulp chamber floor • Retrograde endodontic surgery • Pulpotomy in primary molars • Apexification Ten patients per indication are required in this multi-centre and open-label clinical trial (Machtou. a clinical trial. 32 . 2009b).e. 2009a). like the Portland cements (i.3 . Moreover. 09/001. • Biodentine™ does not require a two step obturation as in the case of MTA. chemical and biological properties are comparable as summarised in the preclinical section.Biodentine™ is used as an endodontic repair material The endodontic indications of Biodentine™ are similar to the usual calcium silicate based materials. • Biodentine™ presentation ensures a better handling and safety than MTA. Biodentine™ could safely be used for each indication where dentine is damaged.6. it is an advantage for the clinician and the patient (Machtou. This type of product is already well documented. However. Therefore. • Biodentine™ consistency is better suited to the clinical use than MTA’s.

Etude de l’effet irritant/corrosif aigü sur l’oeil chez le lapin. 7. Report on going. Boukpessi T. Report RD RA DEV 94-013. Machtou P 2009b Expertise sur l’obturation radiculaire apicale permanente de RD94. Fagette S 2009 RD94. Camps J. Report RG EN RA EXT. Report RG EN RA EXT-RD94/052. 24 (11) 1486-1494.Mater. 5. Tran X. 13. Gomond P 2003a RD94.2006 -. Aubut V. Report RG EN RA EXT-RD94/054. Gomond P 2003c RD94. About I 2003b Etude in vitro sur culture cellulaire de la biocompatibilité du produit RD94: étude des fonctions spécifiques des fibroblastes pulpaires humains.Essai de sensibilisation chez le cobaye . 8. Dent. About I. 9. Etude n° PC08-001. 12. Ligne directrice 405 de l’OCDE (24/04/2002). O’Brien W 2008 Dental Materials and their Selection. De MM. Franquin JC 2001 Etude comparative de la cytotoxicité in vitro de trois produits de restauration coronaire ou radiculaire. and Septier D 2009 Chapter VI Emerging trends in (bio)material researches:VI-1-Repair or regeneration. Report RD RA DEV 94-012. Laurent P. About I 2009 Effets des matériaux bioactifs Biodentine TM et Calcipulpe® sur les étapes précoces de la régénération dentinaire. O’Brien W 4th ed. Etude de RD 94 comme agent pulpaire dans le cadre de pulpotomie et coiffage direct sur les dents lactéales de cochon. and About I 2008 Induction of specific cell responses to a Ca(3)SiO(5)-based posterior restorative material. a short review. 6.Mater.RD94/053. Report RD EN RA EXT-RD94/096. Report RG EN RA EXT-RD94/056. NF EN ISO 10993-10. medical device class III. Gomond P 2003b RD94. 10. 18. Coxmoor Publishing Company (6) : 181-203. Report RG EN RA EXT. Pradelle-Plasse N. Nonat A and franquin JC 2006 Un nouveau matériau de restauration dentaire à base minérale MATERIAUX 2006 13-17 Nov. Harmand MF 2003 RD94. About I 2007 Coiffage pulpaire direct de RD94 à l’aide du modèle de culture de dent entière. Coli). Nomoto R and McCabe JF 2001 A simple acid erosion test for dental water-based cements. 11. Report RD RA DEV 94-006. VI-2. Golberg M 2009 Etude PC08-002. 2.essai par maximisation NF EN ISO 10993-10. Golberg M. Open trial.An example of new material: preclinical multicentric studies on a new Ca3SiO5-based dental material. Report RG EN RA EXT-RD94/050. 17(1) 53-59. 15.RD94/055. RD 94 après implantation à 3 mois dans la première molaire maxillaire de rat. Shayegan A 2009 RD 94. Report RG EN RA EXT-RD94/028. 33 . Assessement of the genotoxicity Ames test (Salmonella thyphimurium and E. not randomized study evaluating the efficacy and the tolerance of RD94 in patients needing endodontic care. 19. 17. About I 2003a Etude in vitro sur culture cellulaire de l’activité mutagène du produit RD94 : test des comètes sur des fibriblastes pulpaires humains. Dent. Laurent P. Machtou P 2009a 09/001. 14.Méthode par classe de toxicité aiguë. Evaluation de la toxicité aiguë après administration par voie orale chez le Rat. 16. Dejou J. 3. Report RD RA DEV 94-010. Essais d’irritation de la peau chez le lapin.References 1. Ed. Report RD EN RA EXT-RD 94 106. 4. colon P.

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