Biodentine: From Biochemical and Bioactive Properties To Clinical Applications
Biodentine: From Biochemical and Bioactive Properties To Clinical Applications
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j o u r n a l h o m e p a g e : w w w. e l s e v i e r. c o m / l o c a t e / g i e
Imad About *
Aix Marseille Univ, CNRS, ISM, Inst Movement Sci, Marseille, France
 * Correspondence to: Institut des Sciences du Mouvement (ISM), UMR 7287 CNRS & Université d’Aix-Marseille, Faculté d’Odontologie, 27 BD
Jean Moulin, 13385 Marseille cedex 5, France.
   E-mail: imad.about@univ-amu.fr.
Peer review under responsibility of Società Italiana di Endodonzia.
http://dx.doi.org/10.1016/j.gien.2016.09.002
1121-4171/ß 2016 Società Italiana di Endodonzia. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND
license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
  Please cite this article in press as: About I. Biodentine: From biochemical and bioactive properties to clinical applications. Giornale Italiano
  di Endodonzia (2016), http://dx.doi.org/10.1016/j.gien.2016.09.002
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2 I. About
    PAROLE CHIAVE                          Riassunto Biodentine è un materiale a base di silicato tricalcico progettato come sostituto
    Biodentine;                            permanente della dentina. Si tratta di un materiale biocompatibile e bioattivo. Le sue interazioni
    Cementi a base di                      con entrambi i tessuti duri e molli portano ad una sigillatura marginale in grado di prevenire
    trisilicato di calcio;                 l’infiltrazione marginale e forniscono una protezione alla polpa sottostante inducendo sintesi
    Sostituti della dentina;               dentina terziaria. A differenza di altri sostituti della dentina, l’applicazione di Biodentine non
    Ricerca;                               richiede alcun condizionamento della superficie dentinale e la tenuta della restaurazione è
    Applicazioni cliniche.                 fornito dalla ritenzione micromeccanica in quanto Biodentine penetra nei tubuli dentinali
                                           formando strutture di simili ai resin-tag. Dopo l’indurimento, il Biodentine può essere tagliato
                                           e rimodellato come dentina naturale. Può anche essere trattato con diversi tipi di adesivi prima di
                                           terminare il restauro definitivo. Studi clinici pubblicati, istologia di denti umani estratti e casi
                                           clinici dimostrano che Biodentine ha un ampio spettro di applicazioni cliniche, come sostituto
                                           permanente della dentina in endodonzia, in odontoiatria restaurativa e odontoiatria pediatrica.
                                           Questa review si propone di descrivere in maniera completa la composizione di Biodentine, le
                                           proprietà di preparazione e il meccanismo di interazione con i tessuti duri e molli. Essa spiega i
                                           meccanismi scientifici che caratterizzano queste funzioni specifiche e illustra la base scientifica
                                           del suo successo nell’utilizzo clinico. L’articolo fornisce inoltre una panoramica delle applicazioni
                                           cliniche di Biodentine riassumendo gli studi clinici e riportando i casi clinici pubblicati con questo
                                           materiale in odontoiatria restaurativa e pediatrica, cosı̀ come in endodonzia.
                                           ß 2016 Società Italiana di Endodonzia. Production and hosting by Elsevier B.V. Cet article est
                                           publié en Open Access sous licence CC BY-NC-ND (http://creativecommons.org/licenses/by-nc-
                                           nd/4.0/)
    Please cite this article in press as: About I. Biodentine: From biochemical and bioactive properties to clinical applications. Giornale Italiano
    di Endodonzia (2016), http://dx.doi.org/10.1016/j.gien.2016.09.002
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be respected and applied according to the manufacturer’s                    replacing dentin and enamel without any conditioning treat-
instructions as these proportions greatly influence the mate-               ment. No leakage was observed when Biodentine surface was
rial’s setting and mechanical properties. This is of particular             prepared with the total etch technique and resin composite
significance mainly for applications under mechanical loads                 application. The results of this investigation demonstrated
such as applications in Class II cavities.                                  that the results obtained with Biodentine were similar to
                                                                            those obtained with resin-modified glass ionomer cement
The setting reaction is a hydration reaction                                (Fuji II LC) considered as a reference material in this type
                                                                            of indications.13 An interesting study compared the shear
When Biodentine powder and liquid are mixed with an amal-                   bond strengths of different adhesive systems to Biodentine.
gamator, the setting of the material is a hydration reaction.               Adhesive systems such as Prime & Bond NT: etch-and-rinse
While Calcium silicates partially dissolve by adding the liquid,            adhesive system, Clearfil SE Bond: 2-step self-etch adhesive
a hydrogel of hydrated silicate is produced. This will pre-                 system and Clearfil S3 Bond: 1-step self-etch adhesive system
cipitate on the remaining Silicate particles’ surface and in the            were applied onto Biodentine discs for 12 min and 24 h then a
spaces between the particles leading to a significant                       Composite (Clearfil Majesty) was applied. Data showed that
decrease in the material’s porosity and an increase in its                  the shear bond strengths were the same for different adhe-
compressive strength over time.9                                            sive systems to Biodentine.14 This confirms that the marginal
                                                                            sealing of Biodentine is equivalent to that of RMGIC (Fuji II
Biocompatibility                                                            LC) and that Biodentine can be etched and treated like
                                                                            natural dentin. Different restorative materials can be suc-
                                                                            cessfully applied on top of Biodentine. Whatever the surface
Like any other restorative material, Biodentine Biocompat-
                                                                            treatment used on Biodentine, this material can be used in
ibility was investigated to ensure its safety when applied onto
                                                                            combination with composite resins.13,14
the cells. Evaluation of its genotoxicity on bacteria strains by
the Ames test and its effects on the formation of micronuclei
by human lymphocytes demonstrated the absence of any
                                                                            Biodentine interacts with hard tissues by
mutagenic effect of the material. Similarly, when tested                    micromechanical retention
on target human pulp cells, no DNA breaks or damage was
observed with the Comet assay. These results demonstrated                   Interactions of Biodentine with the dentin provided cues to
no genotoxic effects of Biodentine in vitro. The biocompat-                 understanding how this material provides a marginal sealing
ibility of the material was also investigated through its direct            without any dentin surface preparation: no etching and no
application to human pulp cells simulating the direct pulp                  bonding. In an experimental work performed ex vivo, dentin
condition and indirectly through a dentin slice to simulate its             slices were prepared and Biodentine was prepared and mixed
indirect pulp capping in vivo. Under both conditions Bioden-                with a fluorescent dye before its application onto the dentin
tine was not found to affect target cell viability under in vivo            surface. Confocal laser scanning electron microscopy and
application conditions.9 Additionally, when Biodentine was                  scanning electron microscopy were used to study the inter-
applied onto human pulp cells to investigate its effects on                 face between Biodentine and dentin. Confocal laser scanning
their specific functions by studying expression of odontoblast              electron microscopy revealed that Biodentine penetrated
specific functions such as expression of Nestin (a human                    into the dentin tubules forming tag-like structures into the
odontoblast specific marker) and Dentin Sialoprotein, Bio-                  dentin tubules. Scanning electron microscopy revealed that
dentine was not found to inhibit the expression of these                    the dentin tubules appeared with plugs of mineralization
proteins but rather induce their expression and the cells                   crystals just beneath the interface obliterating the dentin
mineralization capacity.9—11 Further investigations demon-                  tubules. These results explain the micromechanical reten-
strated the absence of toxicity of Biodentine to human MG63                 tion of the material on the one side and the marginal sealing
human osteoblast cells with the MTT assay with properties                   on the other side.15
comparable to that of MTA.12
                                                                            Bioactive properties in vitro
Interactions with hard tissues: no surface
preparation is needed to apply BiodentineTM                                 An entire human tooth culture model was used to investigate
                                                                            both the material hydration when placed for pulp capping
Clinical application of Biodentine in restorative dentistry                 and its effects on the pulp response. The tooth culture model
implies an intimate interaction with hard and soft tissues                  provides a useful tool to investigate the initial steps of
as well as with other restorative materials. This should lead               dentin-pulp regeneration and the consequence of applying
to a marginal sealing in vivo which provides pulp protection                pulp capping materials. Since the teeth used are immature
and marginal sealing. Thus investigating these properties in                impacted third molars, they also have the advantage of a high
ex vivo is of prime importance.                                             regeneration potential and not to be in contact with the oral
    An experimental work using third molar teeth was used to                flora. Biodentine was applied into pulp cavities then an
investigate the marginal sealing of Biodentine alone or in                  adhesive resin was applied onto Biodentine and overlayed
combination of other resin-based materials using the silver                 with a composite resin. Hydration was allowed to proceed
nitrate penetration method in Class II cavities. No marginal                under conditions similar to those in vivo by incubating teeth
leakage was observed at the Biodentin/dentin interface or at                in culture medium. After 14 days, back-scatter scanning
the enamel/Biodentine interface when the whole cavity was                   electron micrographs revealed that the material was homo-
filled with Biodentine alone as a bulk restorative material                 genous and appeared completely hydrated at all areas
  Please cite this article in press as: About I. Biodentine: From biochemical and bioactive properties to clinical applications. Giornale Italiano
  di Endodonzia (2016), http://dx.doi.org/10.1016/j.gien.2016.09.002
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4 I. About
Figure 1 Biodentine direct application onto human pulp in human entire tooth culture for 4 weeks. Biodentine induced odontoblastic
differentiation and reparative dentin secretion. Mineralization foci containing sequestered cells are observed in the dental pulp
beneath Biodentine. The sequestered cells express odontoblast markers such as Dentin Sialoprotein (DSP) and nestin.10
examined: within the material, at the Biodentine/dentin                       Indeed, after application of Biodentine and culture for
interface, at Biodentine/composite resin interface and at                     14 days, mineralized structures appeared in the form of foci
the Biodentine/pulp interface. The hydration of this type of                  in close vicinity of the material. This mineralization seemed
materials leads to the release of Calcium ions which are                      to be directly linked to Biodentine as some cement particles
necessary for the mineralization. X-ray diffraction analysis                  were seen within the mineralized structures but not in the
of the material after setting demonstrated a significant peak                 neighboring pulp tissue. This mineralized tissue corresponds
of Calcium hydroxide formation which has long been used for                   to an early form of reparative dentin as cells sequestered
pulp capping with a well demonstrated ability to induce                       within these mineralizations express odontoblastic markers
dentin bridge formation.16                                                    such as nestin and dentin sialoprotein (Fig. 1).
   This culture model provided valuable information on the                       This mineralization seems to be due to the release of a
response to Biodentine application directly onto the pulp.                    growth factor, namely Transforming factor beta 1 (TGF-b1)
                                                                              from pulp cells incubated with Biodentine (Fig. 2). This factor
                                                                              has been shown to be involved in odontoblastic differentia-
                                                                              tion and recent investigations revealed that this factor is
                                                                              involved in the recruitment of pulp stem cells to TGF-b1pro-
                                                                              duction site17 which is related to Biodentine application.
                                                                              Interestingly, increase in TGF-b1 was significant whatever
                                                                              the ratio between the Biodentine surface area and cell
                                                                              culture volume.10 This has a clinical significance as it indi-
                                                                              cates that this cement can be applied onto the pulp whatever
                                                                              the injured pulp surface area (Fig. 2).
    Please cite this article in press as: About I. Biodentine: From biochemical and bioactive properties to clinical applications. Giornale Italiano
    di Endodonzia (2016), http://dx.doi.org/10.1016/j.gien.2016.09.002
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that this material can be applied for both pulp capping and                 Formecresol in pulpotomy. The major clinical trials and
pulpotomy. Indeed, Biodentine induced tertiary dentin                       histological studies in human teeth are detailed below and
synthesis when applied as direct or indirect pulp capping                   reported (Table 2) while the clinical case reports are only
material in rat teeth.18,19 After direct pulp capping, the                  listed in the same table.
dentin bridge observed after 4 weeks in rat teeth was tubular
and its porosity was similar to that of MTA.19 Similar results
demonstrated in miniature swine teeth. Indeed, after pulp                   Indirect pulp capping
capping with Biodentine, no pulp inflammation was observed
while a thick dentin bridge formed after 3 and 8 weeks.20                   A randomized clinical study was performed in the restoration
Similar results were reported in primary pig teeth after                    of posterior teeth with Biodentine. 397 cases were included
4 weeks and 90 days. Application of Biodentine in pulpotomy                 with a three years follow-up. Biodentine was applied as a bulk
was also investigated in primary pig teeth and compared to                  restorative material in deep dentin cavities in replacement
formecresol and white MTA (WMTA). The results with Bio-                     of both dentin and enamel. The scoring scales included
dentine showed no inflammation and a thick dentin bridge                    consistency, working time, adhesion to instruments, ease
formed in 90% of the cases.21 These data were comparable to                 of handling, anatomic form, marginal adaption, quality of
the results obtained with WMTA and indicate the biocompat-                  proximal contact, marginal discoloration, surface roughness,
ibility of these materials and their suitability for pulp capping           secondary caries and post-operative pain. The results of this
and pulpotomy.                                                              trial reported that Biodentine was easy to handle, showed, a,
                                                                            excellent anatomic form, marginal adaptation and very good
Clinical applications                                                       interproximal contact. During the follow-up, the restoration
                                                                            with BiodentineTM in comparison to the composite resin Z100
                                                                            was well tolerated in all cases with no post-operative pain.
Although Biodentine is a recently developed material as it has
                                                                            The anatomic form, marginal adaptation and interproximal
been released by the end of the year 2010 in Europe,
                                                                            contact started to deteriorate only after 6 months. Due to the
different clinical applications have been so far published
                                                                            deterioration, a complementary treatment was performed.
with this material. These include applications in restorative
                                                                            Biodentine was kept as dentin substitute as the pulp vitality
dentistry, pediatric dentistry and endodontics. Although it
                                                                            test was positive. Biodentine presented a good resistance to
can be used as a temporary enamel substitute for upto
                                                                            burring and the composite Z100 was applied onto Biodentine
6 months, Biodentine is mainly used as a permanent dentin
                                                                            surface and evaluated for up to 3 years. The conclusions of
substitute. It can be used to replace the missing/damaged
                                                                            this study is that Biodentine can be used as a posterior
bulk dentin volume. It can also be used as an alternative to
                                                                            restoration material for up to 6 months as a temporary
                                                                            enamel substitute. When covered with Z1001, it is a well-
  Table 2 Biodentine clinical applications and type of clinical             tolerated permanent dentin substitute. Additionally, Bioden-
  works published on each application. Biodentine can be used               tine can be cut and shaped like the natural dentin.22 In
  in restorative dentistry, pediatric dentistry and endodontics             another clinical study, the efficacy of Biodentine as an indir-
  as a permanent dentin substitute. It can be used to replace               ect pulp capping material was evaluated and compared to a
  the missing/damaged whole dentin volume. It can also be                   glass ionomer cement (Fuji IX) in irreversible pulpitis. 36
  used as an alternative to formecresol in pulpotomy.                       restorations with Biodentine and 36 Fuji IX were placed
                                                                            randomly in 53 patients. The clinical efficacy at 12 months
  Application                              Type of investigations/
                                                                            revealed no statistically significant differences in clinical
                                           references
                                                                            efficacy between Biodentine and Fuji IX.23
  Crown                                                                         The reported absence of post-operative pain and post-
  Temporary enamel restoration             Clinical trials 22               operative sensitivity in the clinical trial22 may be due at least
  Permanent dentin substitute in                                            to 2 factors:
    Deep/large carious lesions             Clinical trials 22               1) The infiltration of Biodentine into the dentin tubules15 due
    Deep cervical/radicular lesions        Case reports36—38                   to the precipitation of crystals within the tubules
    Indirect pulp capping                  Clinical trials22,23                decreases the dentin tubule permeability and fluid move-
    Direct pulp capping                    Clinical and                        ment which may decrease post-operative sensitivity.
                                           histological studies25,26        2) The reduction odontoblast pain receptor expression and
    Pulpotomy                              Clinical trials27,39                function and the reduction of the secretion of pro-inflam-
  Root                                                                         matory cytokines. Indeed, odontoblasts express pain
    Root canal/furcation                   Case reports 40                     receptors of the transient receptor potential family of
      perforations                                                             ion channels (TRP) namely TRPA1. These receptors play a
    External resorption                    Case   reports 41                   significant role in nociception and neurogenic inflamma-
    Internal resorption                    Case   reports 42                   tion. When extracts of Biodentine were applied on odon-
    Regenerative endodontics               Case   reports 43                   toblast-like cells, expression of these receptors decreased
    Apexogenesis after traumatic           Case   reports33,44                 together with their functional activity as measured by an
      exposure                                                                 intracellular calcium level increase. Additionally, Applica-
    Apexification                          Case reports45—48                   tion of Biodentine decreased the pro-inflammatory tumor
    Retrograde root canal                  Case reports49,50                   necrosis factor secretion (TNF-a) from odontoblast like
      obturation                                                               cells24 as measured by Enzyme-linked immunosorbent
                                                                               assay (ELISA).
  Please cite this article in press as: About I. Biodentine: From biochemical and bioactive properties to clinical applications. Giornale Italiano
  di Endodonzia (2016), http://dx.doi.org/10.1016/j.gien.2016.09.002
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6 I. About
Direct pulp capping                                                           has the potential to be used as a substitute for formocresol in
                                                                              primary molar pulpotomies.
Pulps of 28 non-carious molars scheduled for orthodontic
treatment were exposed mechanically and pulps capped                          Case reports on the other clinical
directly with Biodentine or MTA in class I cavities. 7 patients               applications
complained from mild pain on the day of surgery. 4 of these
patients were treated with Biodentine and 3 with MTA. No                      In addition to the above detailed indications, many case
symptoms were reported in the other patients. Teeth were                      reports have been published with Biodentine in different
tested before extraction for cold and electro-sensitivity and                 clinical indications. These include deep cervical/radicular
all confirmed the pulp vitality. The absence of periapical                    lesions, root canal/furcation perforations, external/internal
pathology was confirmed radiographically before the treat-                    resorption, regenerative endodontics, apexogenesis after
ment and just before the tooth extraction. The histological                   traumatic exposure, apexification and retrograde root canal
examination of the pulp state and response after direct pulp                  obturation. These applications are listed and corresponding
capping with Biodentine as compared to MTA in human teeth                     case report references are provided (Table 2).
revealed an absence of pulp inflammation and the formation
of a complete dentin bridge beneath both materials after
6 weeks.25 Tomographic data evaluating the density and
                                                                              Discussion
volume of reparative dentin revealed that these values were
higher for Biodentine.26 These results indicate that Bioden-                  Although Biodentine is among the most recently developed
tine can be safely applied directly onto the human vital pulp.                tricalcium silicate-based materials, a significant and increas-
                                                                              ing number of investigations have been published on this
                                                                              material. While many studies reported its biocompatibility
Pulpotomy                                                                     and Bioactivity in vitro and in vivo, preclinical investigations
                                                                              shed the light on the mechanisms of its interaction with the
Clinical application of Biodentine in pulpotomy has been                      dental hard tissue. Indeed, many investigations performed
investigated in few clinical studies as a pulpotomy medica-                   both in vitro and in vivo demonstrated that the interactions
ment. A randomized clinical study was performed in children                   of Biodentine with both hard and soft tissues provide a
of 4—9 years of age. 84 pulpotomies were performed and                        hermetic seal protecting the dental pulp by preventing
attributed to MTA or Biodentine. All teeth were restored with                 bacterial infiltration. These studies demonstrated that,
stainless steel crowns. Clinical and radiographic evaluations                 through its interactions with the hard tissues, Biodentine
were performed after 6 and 12 months. Data showed that one                    provides a micro-mechanical retention by infiltrating the
molar of the MTA group had an internal resorption while 1                     dentin tubules. On the other hand it induces the target
molar of Biodentine treated group had internal resorption                     tissue specific functions by inducing tertiary dentin synthesis
and another showed a radiographic radiolucency. Over all,                     which provides further protection to the pulp. These two
both materials had a very high clinical success rate27 and the                combined effects might be responsible, at least in part, for
overall clinical success after 12 months is reported (Table 3).               the absence of post-operative pain and hypersensitivity.
Another study evaluated Biodentine and compared it to MTA                     Another important investigation reported that the applica-
in a short term clinical study. Biodentine was applied in                     tion of Biodentine reduces both TRPA1 pain receptor expres-
pulpotomy in 20 teeth followed by restoration with stainless                  sion and function. More importantly, when applied on
steel crowns. At 3 and 6 months, patients were recalled                       odontoblast-like cells Biodentine decreases pro-inflamma-
and Biodentine was shown as equally efficient as MTA with                     tory TNF-a secretion. This indicates that, in addition to
similar radiographic success.28 A similar study was performed                 the abovementioned roles of Biodentine, its application onto
comparing Biodentine to MTA and Propolis as pulpotomy                         the dentin/pulp reduces the inflammation and consequently
medicaments. After 9 months, Biodentine and MTA showed                        the post-operative pain.
comparable results with a high radiographic success rate and
more favorable than Propolis.29 Finally, a confirmation of all
these data reported no significant differences between MTA
                                                                              How does Biodentine compare to other
and Biodentine used as pulpotomy medicaments even after                       widely used and common pulp capping
18 months with clinical success higher than 95% for both                      materials
materials.30 Taken together, although longer term clinical
evaluations are required, these data indicate that Biodentine                 When compared to Calcium Hydroxide, Biodentine is stronger
                                                                              mechanically due to its composition and low porosity. It is less
    Table 3 Evaluation of Biodentine as compared to MTA in                    soluble and the produced dentin bridge shows no tunnel
    pulpotomy after 12 months. Clinical success rates are                     defects as compared to that under Calcium hydroxide thus
    reported in number of cases and percentage showing a high                 it has a better sealing ability than Calcium hydroxide.19,31
    clinical success rate of both MTA and Biodentine in pulpotomy             When Compared to MTA, Biodentine is easier to handle,22
    after 12 months.27                                                        stronger mechanically and has a shorter setting time.6 It can
                                                                              be used as a temporary enamel substitute up to 6 months and
                    Success/total number of cases         Success (%)         in different applications as a permanent dentin substitute
    MTA             36/39                                 92                  without any surface treatment. Additionally, while discolora-
    Biodentine      38/39                                 97                  tion with MTA32 and its derivatives have been reported in
                                                                              regenerative endodontics and seem to be mainly due to the
    Please cite this article in press as: About I. Biodentine: From biochemical and bioactive properties to clinical applications. Giornale Italiano
    di Endodonzia (2016), http://dx.doi.org/10.1016/j.gien.2016.09.002
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presence of Bismuth oxide as a radio-opacifier,7 no discolora-                    odontoblast-like cells and stimulates biomineralization. JEn-
tion of tooth crown has been reported after 48 months                             dod 2012;38:1220—6.
with Biodentine which does not contain Bismuth oxide but                    12.   Attik GN, Villat C, Hallay F, Pradelle-Plasse N, Bonnet H, Moreau
Zirconium oxide as a radio-opacifier.33—35                                        K, et al. In vitro biocompatibility of a dentine substitute cement
                                                                                  on human MG63 osteoblasts cells: BiodentineTM versus MTA(1).
                                                                                  Int Endod J 2014;47(12):1133—41.
Conclusions                                                                 13.   Raskin A, Eschrich G, Dejou J, About I. In vitro microleakage of
                                                                                  Biodentine as a dentin substitute compared to Fuji II LC in
Taken together, through in vitro, in vivo, clinical trials/                       cervical lining restorations. J Adhes Dent 2012;14(6):535—42.
                                                                            14.   Odabaş ME, Bani M, Tirali RE. Shear bond strengths of different
reports, this review shows that Biodentine is biocompatible,
                                                                                  adhesive systems to Biodentine. Sci World J 2013;10:626103.
has strong mechanical properties and can safely be applied in
                                                                                  http://dx.doi.org/http://dx.doi.org/10.1155/2013/626103.
restorative dentistry, in pediatric dentistry (as a possible                15.   Atmeh AR, Chong EZ, Richard G, Festy F, Watson TF. Dentin-
alternative to formecresol) and in endodontics. It is impor-                      cement interfacial interaction: calcium silicates and polyalk-
tant to know that Biodentine does not require any surface                         enoates. J Dent Res 2012;91(5):454—9.
conditioning treatment. It can be cut and reshaped like                     16.   Camilleri J, Laurent P, About I. Hydration of Biodentine, Theracal
natural dentin. It can be used as a bulk permanent dentin                         LC, and a prototype tricalcium silicate-based dentin replace-
substitute to replace the whole damaged/lost dentin and not                       ment material after pulp capping in entire tooth cultures. J
only as a pulp capping material. Biodentine surface can be                        Endod 2014;40(11):1846—54.
bonded like the natural dentin with different adhesives                     17.   Mathieu S, Jeanneau C, Sheibat-Othman N, Kalaji N, Fessi H,
                                                                                  About I. Usefulness of controlled release of growth factors in
before final composite resins application.
                                                                                  investigating the early events of dentin-pulp regeneration. J
                                                                                  Endod 2013;39(2):228—35.
Conflict of interest                                                        18.   Goldberg M, Pradelle-Plasse N, Tran XV, Colon P, Laurent P, Aubut
                                                                                  V, et al. Emerging trends in (bio)material research. In: Goldberg
The author’s original works on Biodentine were partially                          M, editor. Biocompatibility or cytotoxic effects of dental com-
                                                                                  posites. 1st ed. Oxford, UK: Coxmoor Publishing Company; 2009.
supported by Septodont.
                                                                                  p. 181—203.
                                                                            19.   Tran XV, Gorin C, Willig C, Baroukh B, Pellat B, Decup F, et al.
Acknowledgements                                                                  Effect of a calcium-silicate based restorative cement on pulp
                                                                                  repair. J Dent Res 2012;91:1166—71.
The author thanks Dr. Jean-Charles Gardon for his support by                20.   Tziafa C, Koliniotou-Koumpia E, Papadimitriou S, Tziafas D.
providing the teeth used in the previously published works,                       Dentinogenic responses after direct pulp capping of miniature
Septodont for the continuous support/collaboration and Aix-                       swine teeth with Biodentine. J Endod 2014;40(12):1967—71.
Marseille Université and CNRS institutional support.                       21.   Shayegan A, Jurysta C, Atash R, Petein M, Abbeele AV. Biodentine
                                                                                  used as a pulp-capping agent in primary pig teeth. Pediatr Dent
                                                                                  2012;34(7):e202—8.
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