Biodentine

R&D Department
Biodentine
™
Active Biosilicate Technology™
Scientific File
Summary
Introduction ................................................................................................................................................................. 4
❶ Active Biosilicate Technology™
............................................................................................... 5
1.1 - Setting reaction ..................................................................................................................................................... 6
1.2 - Formulation of Biodentine™ ...................................................................................................................... 7
❷ Physico-chemical features
............................................................................................................... 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
❸ Biodentine™ Interfaces
...................................................................................................................... 14
3.1 - Resistance to acid ........................................................................................................................................... 14
3.2 - Resistance to microleakage .................................................................................................................... 16
3.3 - Electron Microscopy ...................................................................................................................................... 18
❹ 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
❺ 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
❻ 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.
4
❶
Active Biosilicate Technology™
Septodont’s initial objective was to develop a material based on the most biocompatible
chemistry available for dental materials: calcium silicates, which can set in the presence
of water. Although recognized as highly biocompatible and bioactive, all these materials
lack reactivity, with very long setting times (more than 2 hours), low mechanical
properties and with very difficult handling (depending on the water ratio, from a sandy
consistency to a fluid paste).
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, Septodont developed a new technological platform called
Active Biosilicate Technology™. This consists in controlling every step of the material
formulation beginning with the purity of the raw materials.
Usual dental calcium silicate cements are based on the “Portland Cement” materials,
which result from the clinker products manufactured by the building industry from natural
stone treatment. This implies that all these products inherently contain unpurifiable
mixtures of calcium silicates (C3S + C2S), calcium aluminates (C3A), calcium aluminoferrites (C4AF), calcium sulfates (CaSO4 - gypsum), together with low concentrations of
metallic impurities coming from the natural minerals used as raw materials.
The only way to reach our objectives in terms of purity control, high mechanical strength
and short setting times, was to synthesize our own calcium silicate product.
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.
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.
Grinding
Ground
powder
Firing
Biodentine
capsule
5
1.1 - Setting reaction
The calcium silicate has the ability to interact with water leading to the setting and
hardening of the cement. This is a hydration of the tricalcium silicate (3CaO.SiO2 = C3S)
which produces a hydrated calcium silicate gel (CSH gel) and calcium hydroxide (Ca (OH)2).
2(3CaO.SiO2) + 6H2O  3CaO.2SiO2.3H2O + 3Ca(OH)2
C3S
CSH
This dissolution process occurs at the surface of each grain of calcium silicate. 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, due to saturation of the
medium. This precipitation process is reinforced in systems with low water content.
H2SiO422+
Ca O2H
CSH
H2 O
CaOH
Biodentine™ Particle
The unreacted tricalcium silicate grains are surrounded by layers of calcium silicate
hydrated gel, which are relatively impermeable to water, thereby slowing down the effects
of further reactions. The C-S-H gel formation is due to the permanent hydration of the
tricalcium silicate, which gradually fills in the spaces between the tricalcium silicate
grains. The hardening process results from of the formation of crystals that are deposited
in a supersaturated solution.
Powder before hydration
6
Deposition of CSH
Biodentine™ after setting
1.2 - 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, calcium silicates could not be used alone.
Usually calcium silicate cements have setting times in the range of several hours, which
is too long in most of the protocols in clinical practice.
Increasing the setting time was achieved by a combination of different effects. First,
particle size greatly influences the setting time, since the higher the specific surface, the
shorter the setting. Also, adding calcium chloride to the liquid component accelerates
the system. Finally, the decrease of the liquid content in the system decreases the setting
time to harden within 9 to 12 minutes.
Powder
Tri-calcium Silicate (C3S)
Main core material
Di-calcium Silicate (C2S)
Second core material
Calcium Carbonate and Oxide
Iron Oxide
Zirconium Oxide
Filler
Shade
Radiopacifier
Liquid
Calcium chloride
Hydrosoluble polymer
Accelerator
Water reducing agent
Reaching high mechanical strength is also quite difficult for these systems. The first
cause of low mechanical properties of Portland cements are the aluminate components,
which make the product fragile. Septodont controls the purity of the calcium silicate
through the Active Biosilicate Technology™ which consists in eliminating aluminates and
other impurities.
The second axis of formulation was to adjust the particle size distribution in order to
reach an optimal powder density. The additional charge system selected was calcium
carbonate, for both its biocompatibility and calcium content.
The paradox of calcium silicate systems is also that water, which is essential for the
hardening of the product, can also affect the strength of the material. On the hand,
excess water in the system will create some remaining porosity, significantly degrading
the macroscopic mechanical resistance, but on the other hand decreasing the water
content leads to reducing the possibility of a homogenous mix. The addition of
hydrosoluble polymer systems described as “water reducing agents” or super
plasticizers, helps in maintaining the balance between low water content and
consistency of the mixture.
Radiopacity is obtained by adding zirconium oxide to the final product.
7
❷
Physico-chemical features
2.1 - Setting Time
There are several methods to evaluate the setting of dental materials. 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, it corresponds to the setting time. This is the principle of the ISO standard 9917.
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,
2006).
Method:
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. These tests consisted in measuring, by a viscoelastometry,
the constraint transmitted by the sample, when a sinusoidal strain is applied. An ARES
strain-controlled rheometer was used (Rheometric Scientific Inc., Piscataway, US). After
mixing, the sample was inserted between the two striated parallel plates, 6 mm in
diameter, with a 2 mm gap. Only the lower plate was maintained at the controlled
temperature of 37.5°C, and a closed chamber maintained the temperature of the entire
sample at 100% relative humidity to prevent drying. The experimental conditions were
as follows: oscillation frequency: 1 radian per second, applied strain: 0.0005%. Under
these conditions, the applied strain is less than the critical strain beyond which the
structure of the cement paste is altered (about 0.0015%), 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, without any modification of the structure of the
material.
This instrumented method was used to determine the setting time of the Biodentine™
Formulation (Fig.1) and to compare it to a classical glass ionomer (Fuji IX – GC) and
ProRoot® MTA (Dentsply). The initial setting time was determined at the moment when
the elastic modulus begins to increase (10MPa). The final setting time was determined
as the elastic modulus reached 100MPa.
The time between the mixing and the initial setting corresponds to the working time.
8
Fig. 1: Dynamic rheometry evaluation of the initial and final setting times.
Material
PMTA
FUJI IX
BIODENTINE ™
Setting times (Minutes)
Initial
Final
70 (2.58)
175 (2.55)
1 (0.12)
3.4 (0.20)
6 (0.30)
10.1(1.20)
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. The classical glass ionomer sets
faster that Biodentine™ in less than 4 minutes. This represents a great improvement
compared to the other calcium silicate dental materials (ProRoot® MTA), which set in
more than 2 hours.
The setting times of Biodentine™ are in the same range as the amalgams.
When tested according to the ISO standard with the Gilmore needle, 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,
with an amalgam carrier or with carriers which are used for endodontic cements in
retrograde fillings (Messing gun, MTA gun).
In all these cases, 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
2.2 - Density and Porosity
The mechanical resistance of calcium silicate based materials is also dependant on their
low level of porosity. The lower the porosity, the higher the mechanical strength. The
superior mechanical properties of Biodentine™ were determined by the low water
content in the mixing stage. Two different methods confirmed the low porosity of
Biodentine™.
First a mercury intrusion porosimetry method was used. Mercury, the only known liquid
really suitable for porosimetry type measurements, can be forced into pores. The
pressure required to intrude mercury into a pore is determined by the pore diameter. The
samples were prepared under the same conditions as those used for CS measurements.
Measurements were carried out on fourteen 28-day-old cylinders, dried at 40°C in a
primary vacuum for 12 days to eliminate residual water. The porous volume and the
distribution of pore diameters were determined by mercury intrusion porosimetry
(Autopore III, Micromeritics Instruments Corporation, Norcross, USA).
Material
Dens. g/cm3
PMTA
1.882(0.002)
FUJI IX
2.320(0,002)
BIODENTINE ™ 2.260(0.002)
Porous characteristics
Pore V.cm3/g
0.120(0.002)
0.033(0.002)
0.031(0.002)
Porosity %
22.6 (0.2)
7.2 (0.2)
6.8 (0.2)
As expected, Biodentine™ exhibits lower porosity than ProRoot® MTA. The density and
the porosity of Biodentine™ and Fuji IX are equivalent.
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. Impedance spectroscopy technique leads to the increase of
the electrical resistance along with the porosity reduction (Fig.2) (Golberg et al., 2009).
This shows that even
after the initial setting of
Biodentine™,
the
material continues to
improve in terms of
internal structure towards
a more dense material,
with a decrease in
porosity.
Biodentine™
is
an
evolutive material which
improves its mechanical
properties with time.
Fig. 2: Electrical resistance (Ω) versus time (hours)
during setting of Biodentine™
10
2.3 - Compressive strength
Compressive strength is a classical mechanical evaluation of the dental biomaterials
(ISO 9917:1991). Specimens were mixed at room temperature, according to each
manufacturer’s instructions. 6 specimens were prepared using cylindrical Teflon moulds,
4 mm in diameter and 6 mm long, removing air bubbles. 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, for the remaining time
(simulation of the clinical application).
ProRoot® MTA samples were left in the incubator for 24 hours at 37°C and 100% relative
humidity (dry) to allow complete hardening.
Each product was tested at 1 hour, 1 day, 7 days and 28 days. The cylinders were
compressed using a Universal Testing Machine (Model 2/M MTS Systems 1400, Eden
Prairie, Minneapolis, USA), with a cross-head speed of 0.5 mm by minute and the
maximum load was recorded (Fig. 3).
1h
144.2 (6.3) a
131.5 (7.1)b
0.01
24h
7.5 (5.1) a
188.2 (33.1)b
241.1 (13.3)c
≤ 0.001
7d
164.5 (19.3) a
220.6 (16.7)b
253.2 (16.1)c
≤ 0.001
28d
139.9 (35.2) a
185.3 (25.9)b
316.4 (8.7)c
≤ 0.001
Compressive strength (Mpa)
Material
PMTA
FUJI IX
BIODENTINE ™
p value
Time (h)
Fig.3: Comparative evolution of compressive strength after setting
of Biodentine™, Fuji IX and ProRoot® MTA.
The setting of Biodentine™ is illustrated by a sharp increase in the compressive strength
reaching more than 100 MPa in the first hour. The mechanical strength continues to
improve to reach more than 200 MPa at 24h which is more than most glass ionomers
values. A specific feature of Biodentine™ is its capacity to continue improving with time
over several days until reaching 300 MPa after one month. This value becomes quite
stable and is in the range of the compressive strength of natural dentine (297 MPa,
11
(O’Brien 2008)). This maturation process can be related to the decrease of porosity with
time, which was illustrated previously. Biodentine™ is an evolutive biomaterial which
improves its mechanical properties with time.
Comparing the compressive strength of a classical glass ionomer (Fuji IX – GC), at 1 hour,
the compressive strengths are similar. No continuous increase over one month can be
observed with Fuji IX but Biodentine™ is significantly more resistant to compression.
With ProRoot® MTA, even after 1 day, the material has no mechanical resistance. As
classical Portland cement, the mechanical strength develops after several days, reaching
150 MPa after one week.
This demonstrates the superiority of Biodentine™ for building in short time (9-12 min)
sufficient mechanical resistance to be used as a dentine substitute, compatible with
dental restorations.
2.4 - Flexural strength
The 3 points bending test has a clinical significance and is essential when the material
is used for Class I, II and IV cavities. The higher the resistance to flexural strength, the
lower the risk of fracture in clinical use.
The value of the bending obtained with Biodentine™ after 2 hours is 34 MPa. Compared
with that of other materials: 5-25 MPa (conventional Glass Ionomer Cement), 17-54 MPa
(Resin modified GIC), 61-182 MPa (composite resin) (O’Brien 2008), it shows clearly that
the bending resistance of Biodentine™ is superior to conventional GIC, but still much
lower than the composite resin.
The internal values of the flexural strength were 22MPa, very similar to Glass Ionomers
(15-39MPa).
2.5 - Vickers micro hardness
Hardness can be defined as the resistance to the plastic deformation of the surface of
a material after indentation or penetration. Measurements at different times have been
evaluated
The hardness increases in time when cements are immersed in distilled water (Colon in
(Golberg et al., 2009)). After 2 hours, the hardness of Biodentine™ was 51 HVN and
reached 69 HVN after 1 month. These values are comparable to those obtained with
the resin modified GIC-Fuji II LC (36 HVN), and the composite resin-Post Comp II LC
(97 HVN). Calcite is a mineral known to improve the hardness of cements. The formation
of CSH gel reduces the porosity with time. The crystallization of the latter continues,
therefore improving the hardness as well as other mechanical properties (sealing at the
interfaces, compressive strength…).
The reported micro hardness values for natural dentine are in the range of 60-90 HVN
(O’Brien 2008). Biodentine™ has surface hardness in the same range as natural dentine.
12
2.6 - Radiopacity
Biodentine™ contains zirconium oxide allowing identification
on radiographs. According to the ISO standard 6876,
Biodentine™ displays a radiopacity equivalent to 3.5 mm of
aluminum. This value is over the minimum requirement of the
ISO standard (3 mm aluminum).
This makes Biodentine™ particularly suitable in the
endodontic indications of canal repair.
2.7 - 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, Dentsply), we performed several measurements in Septodont’s laboratory:
diametral tensile strength (DTS), flexural strength, elastic modulus, compressive strength
at 24h, Vickers microhardness.
Flexural
Strength
MPa
Modulus
GPa
Compressive
Strength at Microhardness
24h(MPa)
HVN
0,5 mm/min
Product
Lot #
DTS,
MPa
Natural
Dentine
Dental Materials
& their selection
(O’Brien 2008)
-
-
18.5
297
60
Biodentine™
193-A-03.11.08
167-B-19.01.09
16. 0(1.2)
24.0 (7.3)
22.0 (2.3)
213,7 (26,1)
60.9 (5.0)
3M Glass
Ionomer
349270
27.7 (1.0)
26.6 (4.5)
14.9 (2.1)
124.7 (10.3)
77.8 (4.6)
VOCO Ionofil®
Molar AC
915325
16.4 (1.7)
22.5 (2.5)
10.6 (2.9)
129.9 (17.9)
70.3 (3.9)
GC Fuji IX GP
Capsule
902101
16.8 (1.3)
22.8 (1.8)
12.8 (2.8)
130.0 (7.0)
76.8 (3.5)
GC Fuji IX GP
(hand mix)
0811141/
0811031
16.5 (0.5)
14.5 (2.4)
15.4 (3.5)
122.6 (10.1)
72.2 (3.7)
GC Fuji II Light
Cure Capsule
812111
38.1 (1.8)
39.1 (5.4)
8.1 (0.3)
162.8 (10.1)
45.6 (3.9)
GC Fuji II Light
Cure (hand mix)
0902231/
0812081
32.1 (4.2)
19.3 (6.2)
6.3 (0.4)
183.4 (14.8)
43.3 (4.5)
ProRoot® MTA
08003394/
08084
9.5 (1.2)
56.1 (7.2)
Non measurable
Non measurable Non measurable
From this table, it can be concluded that Biodentine™ has a mechanical behavior similar
to glass ionomers and is also similar to natural dentine. The mechanical resistance of
Biodentine™ is also much higher than that of ProRoot® MTA.
13
❸
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, enamel, composites and other dental materials) are
determinative features. This was investigated by erosion in acid solutions, electron
microscopy and microleakage tests.
In the case of Biodentine™, the dissolution/precipitation process, which is inherent to
the setting principle of Calcium silicate cements, will differentiate its interfacial behaviour
from the already known dental materials (composites, adhesives, glass ionomers).
3.1 - Resistance to acid
Concerning durability of water based cements, in the oral cavity; one of relevant
characteristics of the dental materials is the resistance to acidic environment. It is known
that glass ionomers have a tendency to erode under such conditions.
The acid erosion and the effects of aging in artificial saliva on the Biodentine™ structure
and composition were investigated (Laurent et al., 2008).
Methods:
The acid erosion test was evaluated daily in lactic acid (0.02M) and sodium lactate (0.1M)
aqueous solution (pH 2.74), by measuring the height loss of the Biodentine™ samples
(2mm, diameter 30mm) for a week. Aging was evaluated in Meyer-modified Fusayama
artificial saliva containing phosphates (pH 5.3).
The height modification of the material was evaluated for a week. Scanning electron
microscopy was used to examine and characterise the surface of the sample before and
after Aging. The possible dissolution of the new material in the artificial saliva was
evaluated by measuring the concentration of Si, Ca, Zr, and inorganic carbonate in the
artificial saliva after 1, 2, 3 and 4 weeks.
Results :
In the 2.74 pH solution, acid erosion is observed (Fig.4), but this erosion is slower than
with glass ionomer cement reported by Nomoto (Nomoto and McCabe, 2001).
14
In artificial saliva there was no erosion but deposition of white material on the surface of
the Biodentine™ sample. Scanning electron microscopic analysis of this material revealed
needle-like crystals with an apatitic appearance. The composition of this deposit by
X-diffraction analysis seems to confirm the apatitic composition (ratio Ca/P = 1.6). This
correlates well with the analysis of the elements in the solution, which revealed a
decrease of Ca concentration with time, which in turn, corresponds to the precipitation
of apatite-like calcium phosphate crystals.
500
Depth (µm)
400
Biodentine
300
Ketac Fil
200
Fuji II
100
0
50
100
150
200
time (h)
Fig.4: Acid erosion profile in pH=2.74, lactic acid/lactate solution
Apatite-like crystal deposition on the surface of Biodentine™
in a phosphate containing artificial saliva solution (pH=5.3)
As a conclusion, the erosion of Biodentine™ in acidic solution is limited and lower than
for other water based cements (Glass Ionomers). In reconstituted saliva (containing
phosphates), no erosion is observed. Instead, a crystal deposition on the surface of
Biodentine™ occurs, with an apatite-like structure.
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
deposition of apatitic structures might increase the marginal sealing of the material.
This type of crystal deposition is already well known for MTA systems.
15
3.2 - Resistance to microleakage:
Several studies were performed to evaluate the resistance of Biodentine™ to
microleakage.
The interface with dentine and enamel was examined using dye penetration methodology
(silver nitrate), which is one of the most commonly used assays to assess, in vitro, the
interfacial seal, by measuring the percolation of a dye along the different interfaces
studied (Golberg et al., 2009).
Methods:
Freshly extracted human molars were used to prepare class II cavities both on the mesial
and on the distal sides. The prepared teeth were divided into different groups to evaluate
the influence of a pretreatment of the cavity using polyacrylic acid solution (GC Conditioner,
GC Corp.) before Biodentine™ placement, the application of a surface varnish (Optiguard®,
Kerr) after the Biodentine™ setting to protect from humidity after initial setting and the
influence of the bonding agent (Xeno® III, Dentsply or G Bond, GC) when placing a
composite (Ceram-X® Mono, Dentsply) over Biodentine™ one day after setting.
Each group was submitted to 2200 thermocycles (5°C – 55°C, 10 seconds for each batch
and transfer). The percentage of microleakage was determined on six samples as the
length of dye penetration divided by the length of the interface.
•At the enamel - BIODENTINE™ interface:
% Dye penetration = (AA1/AB) * 100%
• At the dentin - BIODENTINE™ interface:
% Dye Penetration = (CC1/CD) * 100%
• At the composite - 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, with or without polyacrylic acid
treatment. The placement of a protective varnish increases microleakage at the enamel
interface in the early stage, but not at the dentine interface. After 3 months of aging, no
significant difference could be evidenced in the case of Optiguard® placement or not.
At the Biodentine™-composite interface (Fig.5), 1 day after placement, the specimens
bonded with Xeno® III exhibited significantly less microleakage than those bonded with
G Bond.
After 3 months, the micro leakages of specimens treated with G Bond were lower than
at 1 day. At 3 months no significant differences at the composite-Biodentine™ interface
were observed between Xeno® III or G Bond and Xeno® III + Optiguard®.
16
Fig. 5: Histogram of mean microleakage % at the
Biodentine™ / adhesive interface
According to this study, 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), are very resistant to micro leakage, with or without pre-treatment by polyacrylic
acid solutions. The choice of water based adhesive systems might be preferable when
placing a composite over Biodentine™. The sealing quality of Biodentine™ is not
influenced by the storage after 3 months.
Dejou evaluated the micro leakage resistance of Biodentine™ in comparison with one
of the best sealing systems, resin modified glass ionomers (Fuji II LC, GC Corp.): after
2500 thermo cycles, 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).
Mesio-occlusal and disto-occlusal preparations below cementum-enamel junction were
made in 42 extracted molars. The teeth were randomly assigned one of the following
treatments before restoration with Filtek™ Z250 (3M ESPE) composite resin:
Biodentine™; Fuji II LC (GC); Biodentine™ + Optibond® Solo Plus (Kerr); Biodentine™
+ Optibond® Solo Plus (Kerr) + silane; Biodentine™ + Septobond SE (Septodont) ;
Fuji II LC (GC) + Optibond® Solo Plus (Kerr).
5 mm
Concerning the first two groups: leakage was evaluated
separately, in contact with enamel or in contact with dentine
(Fig.6). Biodentine™ exhibits better leakage resistance both to
enamel and to dentine compared to Fuji II LC.
2 mm
6 mm
2 mm
Fig.6: Micro leakage scores of Biodentine™ or Fuji IILC in contact with enamel or dentine
17
Z 250
6
Optibond
Solo+
In the sandwich technique groups, at the
interface between the base material
(Biodentine™ or Fuji II LC) and the composite,
in case of Optibond® Solo plus (total etch
system), similar micro leakage resistance are
obtained (Fig.7).
Biodentine
FujillLC
Only in the case of Septobond SE (self etch
bonding), was the percolation at the interface
slightly increased, but no significant
difference could be evidenced on the maximal
median scores.
Fig.7: Micro leakage scores of Biodentine™
or Fuji IILC in sandwich technique
In conclusion, Biodentine™ has a similar
behavior in terms of leakage resistance as Fuji
II LC at the interface with enamel, with dentine
and with dentine bonding agents.
Biodentine™ is then indicated in opensandwich class II restoration without any
preliminary treatment.
3.3 - Electron Microscopy:
Interface between Biodentine™ (left) and
human dentine (right): the two surfaces are in
direct and intimate contact. The surface of
Biodentine™
presents
some
crystal
deposition which appeared after the sample
cutting due to re-exposition to water
environment.
Pr Dejou, Dr Raskin
There is a direct contact without a gap
between Biodentine™ and the natural dentine.
The crack is observed inside Biodentine
caused by dehydration, due to SEM sample
preparation under vacuum. This cohesive
failure does not affect the dentineBiodentine™ interface, which indicates the
quality of the micro-mechanical adhesion.
Pr Colon, Dr Pradelle
18
At the entrance of the dentine tubules, some
mineral re-crystallisation occurs, creating
mineral tags. This induces micromechanical
anchorage of Biodentine™. This process
will continue with time, improving the
sealing.
Crystallisation process in the dentine
tubule of an extracted wisdom tooth
treated with Biodentine™, observed after
28 days of storage in distilled water.
The dentine tubules are obturated by recrystallisation.
Pr Colon, Dr Pradelle
Dr Franquin
Comparison of the interface
between Biodentine™ or Fuji
II LC and a composite, using
Optibond® Solo Plus: The
interfaces are very similar.
Pr Dejou, Dr Raskin
Perfect seal of Biodentine™ in contact with radicular dentine, as well as between two
increments of Biodentine™, in an in vitro test of apexification.
Dr Bronnec, Pr Colon
19
❹
Outstanding biocompatibility
From a regulatory point of view, Biodentine™ is a calcium silicate based material, used
for crown and root dentine repair treatment, involving external contact for a period of
more than 30 days. The biocompatibility tests required for the preclinical evaluation of
dental products followed the guideline ISO 7405 - 2008.
The following sections evaluate the compliance with this standard for the tests carried
out on Biodentine™. It is considered a device with external contact, for long-term tissue
contact (>30 days). In certain indications (radicular, apical obstruction and repair of the
pulpal floor), it can be considered an implanted system, according to the ISO
classification.
All biocompatibility tests were carried out on the final product Biodentine™.
4.1 - Cytotoxicity tests (ISO 7405, ISO 10993-5)
Different cytotoxicity tests carried out on Biodentine™ are reported.
The first study was performed on human pulpal fibroblasts (human wisdom tooth),
comparing Biodentine™, calcium hydroxide and MTA (Dycal®, Dentsply and ProRoot®
MTA Dentsply). The cell viability was determined by MTT incorporation (About, 2003b).
Results showed Biodentine™ was non cytotoxic like MTA, whereas the undiluted cement
Dycal® induced 22 % of cytotoxicity (Table. 1).
Product
Biodentine™
MTA
CaOH
Cell death (%)
0±8
0±9
22±10
Table 1. Cell death after Dycal®, MTA
and BIODENTINE™ contact.
Collagen
Moreover, the cell differentiation was evaluated
with the expression of collagen, dentine
sialoprotein (DSP) and osteonectin (OSN).
Results showed the expression of the
differentiation markers, underlining the safety
of Biodentine™ (Fig. 8).
DSP
Control
Biodentine™
(4 weeks)
MTA
(4 weeks)
20
Figure 8. Expression of
collagen and dentine
sialoprotein (DSP) after
contact with Biodentine™
and MTA during 4 weeks.
The second study was performed on L929 fibroblasts comparing Biodentine™,
composite resin Filtek™ Z250 and MTA (Franquin, 2001). Samples were extracted 3 h,
24 h and 7 days after the setting. The cell viability was determined by MTT incorporation.
Results showed Biodentine™ is not cytotoxic (< 10 %) whatever hardening time is
considered. Filtek™ Z250 resin is slightly cytotoxic (> 20 %) at the 3 observation
periods (Table 2).
Product
Filtek™ Z250
MTA
Biodentine™
3 hours
23%
0%
2%
1 day
25%
14%
10%
7 days
26%
8%
9%
Table 2. Cell death after Filtek™ Z250, MTA and Biodentine™ contact.
The third study was published in Dental Materials on the biological effects of
Biodentine™ (Laurent et al., 2008). They were compared to those induced by the
materials used for pulp capping such as MTA and Dycal®. Several tests were carried out:
• A cytotoxicity test involving indirect contact through a section of dentine: none
of the tested materials was cytotoxic.
• Where there is no dentine interposition, 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.
• Differentiation of pulp fibroblasts in orthodontoblastic cells was also analysed
for contact with two materials. Pulp fibroblasts secrete a mineralised matrix
and cells in contact express differentiation proteins (nestin and dentine sialoproteins). Once the cells had been in contact with Biodentine™ cement or with
MTA, marker expression was important in the pulp cells involving the formation
of mineral nodules. Immunological marking was in all cases higher in the cells
forming mineral nodules.
To conclude, 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, dental
specialised pulp cells and that moreover it does not affect phenotypic pulp expression
of fibroblasts.
4.2 - Sensitization tests (ISO 7405, ISO 10993-1)
Studies were performed on guinea-pigs thanks to a maximisation method (intradermic
and topical application with Freund complete adjuvant induction.
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. The
sensitisation potential is graded (class 0 to 4) according to the percentage of sensitised
animals (score of more than 2).
Biodentine™ was not sensitizing (Gomond, 2003c).
21
4.3 - Genotoxicity tests (ISO 7405, ISO 10993-3, OCDE 471)
Several genotoxicity tests were performed on the Biodentine™ cement. They were
carried out on extracts of the cement after complete setting.
AMES test performed on Salmonella typhimurium and Escherichia coli. Strains TA98,
TA100, TA1537, TA1535, pKM101 in absence or presence of metabolism activator.
Results showed that Biodentine™ was not mutagenic (Harmand, 2003).
Another AMES test was performed on 4 strains of Salmonella typhimurium TA97A, TA98,
TA100 and TA102. The results showed that cement Biodentine™ does not induce reverse
mutation in the presence or absence of the metabolic activator S9. Identical results were
reported for the four strains of bacteria tested (Laurent et al., 2008).
An in vitro micronucleus test was also carried out using human lymphocytes (Laurent et
al., 2008). These were exposed to extracts of Biodentine™ obtained either from a culture
medium or DMSO. Dilutions of 1% to 5% of the extracts were used. After a culture time
of 72 hours, the cells were stained and analysed. 1000 bi-nucleated lymphocytes were
tested, to check for a micronucleus. A toxicity index was determined, together with a
ratio for the number of micronuclei in relation to the negative reference. The results
showed that after incubation of the lymphocytes with different dilutions of the extract of
Biodentine™, the number of lymphocytes presenting a micronucleus was similar to that
obtained with the negative reference (3.9% to 4.1%) when concentrations of 1% to 5%
in an aqueous or hydrophobic medium were tested. Positive controls produced a
micronucleus rate of 16% (Fig. 2)
Biodentine™
1%
2.3%
3.7%
5%
- control
+ control
Micronucleoted
lymphocytes (%±SD)
4.0±1.1
4.0±1.1
4.0±1.2
4.2±1.2
3.7±1.2
16.0±6.0*
Table 3. Micronucleated lymphocytes
after contact with Biodentine™ .
Biodentine™
dilution
0.1%
1%
10%
Undiluted
Negative control
Positive control
Tail DNA mean
(%±SD)
12.59±0.96
13.31±0.88
14.90±1.06
15.58±1.08
13.19±0.96
46.52±1.45*
Table 4. Tail DNA mean after contact
with Biodentine™.
22
Finally, the comet test on human pulp
fibroblasts was conducted (About, 2003a).
The extract of Biodentine™ was prepared in
DMSO and a culture medium, at 50 mg/ml for
24 hours and at 37°C. The cells were exposed
directly to increasing dilutions of cement
extracts for two hours. Following electrophoresis, the slides were analysed by
fluorescent microscopy (magnification 400)
and an automated analyser was used to
determine DNA lesions. The results obtained
showed that the percentage of tail DNA varied
from 12.59 for a dilution of 0.1% to 15.58 for
the undiluted medium. It was 13.19 for the
negative control and 46.52 for the positive
control (Table 3). In the presence of DMSO,
there was no significant difference between
the genotoxicity of Biodentine™ and the
negative control (extracted with NaCl and
DMSO).
4.4 - Cutaneous irritation tests (ISO 7405, ISO 10993-10)
Cutaneous irritation test was performed in the rabbit by direct application. Oedema and
erythmea were evaluated 1h, 24h, 48h and 72h after patch removal. Biodentine™ was
shown to be non irritant (Gomond, 2003a).
4.5 - Eye irritation tests (OCDE 405)
The irritation of the liquid part of Biodentine™ was tested on rabbit eye mucosa. 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 0.1 ml on eye in
3 rabbits. The ocular reactions (redness and chemosis of conjunctivae, iris and cornea
lesions) were scored 1h, 24h, 48h and 72h after application. The liquid part of
Biodentine™ undiluted was unclassified among the chemicals irritating to eyes (Fagette,
2009).
4.6 - Acute toxicity tests (ISO 7405, ISO 10993-11,
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. Rats were observed
immediately after administration, 1h, 2h, 3h, 4h, and at least once a day during 14 days.
The administration by oral route of the 2000 mg/kg dose of Biodentine™ induced no
acute toxicity in the rat. The DL50 of Biodentine™ is superior to 2000 mg/kg (Gomond,
2003b).
4.7 - 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, mutagenic, irritant or sensitising
agent. It is devoid of oral toxicity at a dose of 2000 mg/kg. In conclusion, Biodentine™
is safe. Compared to well known dental materials such as Dycal® (calcium hydroxide),
Biodentine™ exhibits less cytotoxicity. Moreover, when compared to ProRoot® MTA,
Biodentine™ demonstrates at least equivalent biocompatibility.
23
❺
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.
5.1 - 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, 2007). The teeth (n = 15) were cultured for 24 hours
(n = 5), 14 days (n = 5) and 28 days (n = 5) in order to determine the bioactivity of
Biodentine™ (Fig 9).
A
B
C
Figure 9. Exposed pulp cavities (A) obturated with Biodentine™ (B) and cultured (C).
At the end of the culture and after demineralisation, histological sections were done. The
results showed good preservation of the pulp up to 28 days. Near the capped area, a
change in the pulp tissue was reported, with the neo-formation of reparatory dentine
comparable to that observed with MTA (Fig 10). This corresponds to the first signs of
the formation of a dentine bridge.
Figure 10. Observations after 28 days.
To conclude, Biodentine™ is able to stimulate initiation and development of mineralization.
24
5.2 - In vitro test for angiogenesis
A study was conducted on damaged pulp fibroblasts in order to evaluate the
Biodentine™ activity on angiogenesis (About, 2009). This model mimicked the in vivo
situations in cases of pulp damage requiring direct pulp capping. Materials such as
Biodentine™, Calcipulpe®, Hydroxide de calcium XR, ProRoot® MTA and Xeno®III were
applied to the cells and growth factors (VEGF, FGF-2, PDGF-AB, TGF-β1) concentrations
were evaluated by ELISA test.
Results showed that none of the products modified the cell structure in this model. Only
ProRot® MTA and Biodentine™ were able to stimulate the formation of mineralisation
spots. The concentration level of TGF-β1 was enhanced by both ProRoot® MTA and
Biodentine™. Moreover, VEGF and FGF-2 were enhanced in presence of Biodentine™
(150 à 200% for VEGF and up to 670 % for FGF-2).
These results suggest that Biodentine™ is able to stimulate angiogenesis, in order to
heal pulp fibroblasts.
5.3 - Stimulation of reactionary dentine in indirect pulp
capping : rat model
A study was conducted on the maxillary molars of adult rats (Golberg, 2009). The first
maxillary molars were prepared in order to achieve half-moon cavities (class V) on the
mesial face. The cavities were filled with Biodentine™ and with Fuji IX glass ionomer
cement and covered with a protective varnish. The teeth were collected and fixed at 8
days, 15 days, 30 days and 3 months after filling. The results showed that after 8 days,
pulp inflammation was moderate in the mesial third of the pulp chamber. This reaction
was also observed on the reference teeth (Fig. 11).
Figure. 11. Biodentine™ stimulates reactionary dentine (rd).
25
The inflammatory process had disappeared after 15 days. The newly formed reactionary
dentine was identified. By comparison with the group treated with the glass ionomer
cement, 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, 40 to
80 µm after 15 days and 140 to 280 µm after 30 days, although it varied between 10
and 20 µm for the reference group. After 3 months, reactionary dentine generated by
Biodentine™ was thick and dense (Fig. 12), enclosing the horn and the mesial pulp whilst
for Fuji IX, this was less dense, only partially covering the mesial cervical area of the pulp
(Golberg, 2009).
Fig. 12. Formation of a thick reactionary dentine in presence of to Biodentine™ in comparison to Fuji IX
To conclude, Biodentine™ was able to stimulate a reactionary dentine which is a natural
barrier against bacterial invasions. The reactionary dentine formation stabilises at
3 months, indicating that the stimulation process is stopped when a sufficient dentine
barrier is formed.
5.4 - Calcification as a result of Biodentine™ in a direct
pulp capping and pulpotomy : pig model
Two protocols were set up in pigs (Shayegan A, 2009).
The first protocol was the analysis of the pulp reaction following pulpotomy and
placement of different materials (15 deciduous teeth, 15 pigs):
• Formocresol
• White MTA
• Biodentine™
The follow-up was performed during 1, 4 and 12 weeks.
Pulp chamber was excised in 15 pigs in a comparative study of the efficacy of
Biodentine™ versus formocresol and MTA (5 pigs per group). Histological sections of
the teeth were done after a week, a month and 3 months of treatment. The results
showed that Biodentine™, like White MTA, promoted beneficial calcification after one
week, whereas Formocresol induced necrosis and inflammation (Fig. 13).
26
Formocresol
WMTA
Biodentine™
1 week
Inflammation
10/10 Necrosis and inflamation 6/10 Beginning of calcification 10/10 Calcification
4 weeks
InflammationTissu regeneration
transition
12 weeks
Complete healing
4/10 Necrosis and inflamation 7/10 Important calcification
5/10 Infiltration of inflammatory
7/10 Important calcification
cells
7/10 Necrosis and inflamation
1/10 Calcification
10/10 Complete calcification
9/10 Complete calcification
Fig. 13. Summary of pulpotomy results.
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, 15 pigs):
• Ca (OH)2
• White MTA
• Biodentine™
The follow-up was performed during 1, 4 and 12 weeks.
Pulp exposure was performed via a class V vestibular cavity in 15 pigs who were
4 months old, 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).
Calcium hydroxyde
WMTA
Biodentine™
1 week
Inflammation
2/10 Calcification
7/10 Calcification
9/10 Calcification
InflammationTissu regeneration
transition
7/10 Important calcification
5/10 Partial calcification
10/10 Important calcification
10/10 Important calcification
12 weeks
10/10 Important calcification
10/10 Important calcification
9/10 Important calcification
4 weeks
Complete healing
Fig.14. Summary of direct pulp capping results.
27
To conclude, Biodentine™ enhances the formation of a dentine barrier after direct pulp
capping confirming it has good potential in this indication. In the first month, the quality
of the dentine bridge formed with Biodentine™ is of better quality than with the reference
dental technique (calcium hydroxide). The performance of Biodentine™ is at least
equivalent to White MTA.
5.5 - Overall bioactivity
Pulp capping and pulpotomy studies showed that Biodentine™ was very well tolerated.
Moreover, Biodentine™ was able to promote mineralisation, generating a reactionary
dentine as well as a dense dentine bridge. These phenomena illustrate the great potential
for Biodentine™ to be in contact to the pulp, by demonstrating its bioactivity in several
indications.
As a conclusion, Biodentine™ is bioactive.
28
❻
Clinical efficacy
6.1 - Biodentine™ is used as a dentine substitute under
a composite
A clinical investigation, 04/001, aimed to assess the acceptability of Biodentine™ as a
new restoration of the posterior teeth: a first-in-man study.
Among the products already used in dentistry, one product shares similar properties with
Biodentine™. This product, MTA, Mineral Trioxide Aggregate, sold by Dentsply under
the brand name ProRoot® MTA, is a derivative of Portland cement, with the same
chemical properties. It was developed as a product for radicular repair only, due to a
low compressive strength incompatible with restorative indications. The biological
properties of this product allow its use in the capping of dental pulp tissue, in the filling
of the radicular apical part by a retrograde approach or in the closure of perforations, to
promote the restoration of the original tissue in contact with the pulp tissue and radicular
tissue.
Biodentine™ can be defined as a special micronised concrete derived from the main
component of Portland cement, tricalcium silicate. With physical properties far superior
to those of MTA, especially in terms of setting time and compressive strength, it exhibits
the same characteristics of biocompatibility and sealing ability, after setting in an alkaline
pH, with controlled (size and spatial organisation) formation of calcium salts. This product
exclusively composed of mineral components, was initially designed to replace dentine
in restorations.
In this study, Biodentine™ is compared to Filtek™ Z100, which is used for dental
restorations and requires an adhesive for the bonding the composite on the tooth.
Biodentine™ is applied directly to contact with the tooth, without adhesive or conditioner.
This clinical investigation is a multicentre, randomised, prospective study, which required
the inclusion of 400 patients and a 3-year observation period.
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. Among the 116 restorations done
with Biodentine™, 20 involved a direct pulp capping.
The study planed a follow-up at baseline, 15 days, 6, 12, 24 and 36 months. The analysis
of the cases showed:
At D0, Biodentine™ showed:
• Easy handling.
• Excellent anatomic form.
• Very good marginal adaption.
• Very good interproximal contact.
29
During the follow-up, the restoration with Biodentine™ in comparison to Filtek™ Z100:
• Was well tolerated in all cases.
• The anatomic form, the marginal adaptation and the interproximal contact
started to degrade after 6 months.
• Due to the degradation, a complementary treatment was performed. In 93.8%,
cases needed a retreatment (92/116); 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.
The tolerance was evaluated for up to 3 years.
• Was safe for the patient, as the same number of adverse events was observed
in Biodentine™ group (4/116) as in Filtek™ Z100 group (3/116).
As a conclusion, Biodentine™ was applied in 116 patients with at least one year follow-up.
Thanks to its excellent biocompatibility, Biodentine™ is very well tolerated and can be
used as cavity lining with a permanent composite restoration (Fig.15).
D0 : Patient restoration
D0 : Amalgam removal
6 months later
16 months:
Biodentine™ reshaping
Fig. 15.Restoration with Biodentine™
(Courtesy of Prof. KOUBI, Marseille).
30
D0 : Biodentine™ application
30 months later:
Biodentine™ under Filtek™ Z100
6.2 - Biodentine™ is used as a direct pulp capping
material
In the same clinical trial, 04/001, Biodentine™ was also used as direct pulp capping
material. Biodentine™ showed:
• An excellent tolerance.
• The ability to save pulp vitality even in difficult cases: the vitality test was
positive at each recall.
Moreover, Biodentine™ can be used in direct pulp capping indications with a good
success rate (Fig. 16). 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.
D0 : Radiography
D0 : Exposed pulp
D0
D0 : Biodentine™ application
Three years later: Biodentine™ covered
by Filtek™ Z100.
Fig. 16. Direct pulp capping with Biodentine™ (Courtesy of Prof. KOUBI, Marseille).
31
6.3 - Biodentine™ is used as an endodontic repair
material
The endodontic indications of Biodentine™ are similar to the usual calcium silicate based
materials, like the Portland cements (i.e. ProRoot® MTA). This type of product is already
well documented.
Several physical, chemical and biological properties are comparable as summarised in the
preclinical section. However, Biodentine™ has some features which are superior to MTA.
• Biodentine™ consistency is better suited to the clinical use than MTA’s.
• Biodentine™ presentation ensures a better handling and safety than MTA.
• Biodentine™ does not require a two step obturation as in the case of MTA.
As the setting is faster, there is a lower risk of bacterial contamination than
with MTA.
Adding to its ability to be used as dentine substitute, Biodentine™ could safely be used
for each indication where dentine is damaged. Therefore, it is an advantage for the
clinician and the patient (Machtou, 2009b).
Moreover, a clinical trial, 09/001, aimed at assessing the tolerance and efficacy of
Biodentine™ in 6 endodontic procedures, 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, 2009a).
32
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