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Response of Human Dental Pulp Capped with Biodentineand Mineral Trioxide Aggregate

 Alicja Nowicka, DDS, PhD,*  Mariusz Lipski, DDS, PhD,†  Miros1aw Parafiniuk, MD, PhD, ‡ 

 Katarzyna Sporniak-Tutak, DDS, PhD, §  Damian Lichota, DDS, PhD,*  Anita Kosierkiewicz, MD, PhD,jj Wojciech Kaczmarek, DDS, PhD,* and Jadwiga Buczkowska-Radli nska, DDS, PhD * 

 Abstract

Introduction: Biodentineis a newbioactive cementthatis similar to the widely used mineral trioxide aggregate(MTA). It has dentin-like mechanical properties, whichmay be considered a suitable material for clinical indica-tions of dentin-pulp complex regeneration such as directpulp capping. The purpose of the present study was to

compare the response of the pulp-dentin complex inhuman teeth after directcapping with this newtricalciumsilicate–based cement with that of MTA.   Methods:

Pulps in 28 caries-free maxillary and mandibular perma-nent intact human molars scheduled for extraction fororthodontic reasons were mechanically exposed and as-signed to 1 of 2 experimental groups, Biodentine orMTA, and 1 control group. Assay of periapical responseand clinical examination were performed. After 6 weeks,the teeth were extracted, stained with hematoxylin-eosin, and categorized by using a histologic scoringsystem.   Results:   The majority of specimens showedcomplete dentinal bridge formation and an absence of inflammatory pulp response. Layers of well-arranged

odontoblast and odontoblast-like cells were found toform tubular dentin under the osteodentin. Statisticalanalysis showed no significant differences betweenthe Biodentine and MTA experimental groups duringthe observation period.  Conclusions: Within the limita-tions of this study, Biodentine had a similar efficacy inthe clinical setting and may be considered an interestingalternative to MTA in pulp-capping treatment duringvital pulp therapy.   (J Endod 2013;39:743–747)

Key WordsBiodentine, direct pulp capping, histology, MTA, pulpalreaction

The application of biocompatible materials on exposed pulp protects the pulp-dentincomplex against chemical irritation by operative procedures, toxicity of the material 

used, and bacterial penetration due to microleakage (1–5). Numerous studies haveshown that Ca(OH)2   should be the material of choice among the available pulp-capping materials  (6–8). However, it has been reported that Ca(OH)2   does not adhere to dentin and dissolves over time, and dentin bridges adjacent to the material 

may contain multiple tunnel defects (9–12).Studies have shown that mineral trioxide aggregate (MTA)may be used as an alter-native to Ca(OH)2 for treating pulpwounds (2, 13). MTA stimulates formation of dentinbridges faster than calcium hydroxide (2, 11, 13–15), consequently leading to pulphealing, and results in high success rates in clinical procedures (13–16). However,in research by Iwamoto et al  (6), no significant differences in clinical and histologicresults between MTA and calcium hydroxide were noted. Also, 2 randomized controlledstudies have shown that MTA may result in similar clinical outcomes as calciumhydroxide after capping caries pulp exposures   (7, 8). MTA is a bioactive,biocompatible, antibacterial material with unique stability and high sealing ability (6, 11, 13–17). However, MTA is reportedly difficult to use because of its longsetting time, poor handling properties, high material costs, and the discolorationpotential of dental tissue (17, 18). Many attempts have been made to improve theclinical manageability of MTA by adding a setting accelerator or a dual functional 

modifier (19, 20). The addition of CaCl 2 to MTA enables an increased immediate pH value and decreased setting time and improves the mechanical properties (1, 19,20). To prevent discoloration, the manufacturer introduced a new MTA formula withan off-white color (18), but white MTA has a significantly slower setting time compared with gray MTA  (21).

Biodentine (Septodont, Saint Maur des Fosses, France) is a new calcium silicate–based restorative cement with dentin-like mechanical properties, which can be used asa dentinsubstitute on crownsand roots similar to how MTAis used (3,4, 22–26).Ithasa positiveeffect on vital pulpcells and stimulates tertiary dentin formation(3,4,26,27).In direct contact with vital pulp tissue, it also promotes formation of reparative dentin(3, 26). Biodentine consists of a powder and liquid. The powder mainly containstricalcium and dicalcium silicate (3CaO SiO2   and 2CaO SiO2), the principal component of Portland cement, as well as calcium carbonate (CaCO3). Zirconium

dioxide (ZrO2) serves as contrast medium. The liquid consists of calcium chloride(CaCl 2$2H2O), which is used as a setting accelerator and water-reducing agent inaqueous solution with an admixture of polycarboxylate (a superplasticizing agent)(3, 26). The consistency of Biodentine is similar to that of phosphate cement. Thematerial can be applied directly in the restorative cavity with a spatula as a bulk dentin substitute without any conditioning treatment  (3, 22–26).

The enhanced clinical manageability of MTA may be more convenient for dentistsduring endodontic treatments; however, it is important to note that changes in thechemical components of MTA may adversely affect its physical and possibly its bioactiveproperties.  In vivo studies are required to understand the pulp response when MTA isused for direct pulp capping. Studies on animal teeth (1, 12, 14, 19) and human teeth(2, 5–8, 10, 11, 13, 15, 16) have demonstrated the various effects of applying MTA as

From the *Department of Conservative Dentistry,†Department of Preclinical Conservative Dentistry and Preclin-ical Endodontics,   ‡Department of Forensic Medicine,§Department of Dental Surgery, and  jjDepartment of Pathology,Pomeranian Medical University, Szczecin, Poland.

Address requests for reprints to Dr Alicja Nowicka, Pomer-anian Medical University, Department of ConservativeDentistry, Al.Powstancow Wlkp. 72, 70–111 Szczecin, Poland.E-mail address: nowicka6@gmail.com0099-2399/$ - see front matter

Copyright ª 2013 American Association of Endodontists.http://dx.doi.org/10.1016/j.joen.2013.01.005

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a pulp-capping agent; to our knowledge, no clinical investigation hascompared Biodentine and MTA in humans, although one animal study has been published (26).

The purpose of the present study was to evaluate the clinical,radiographic, and histologic responses of the pulp-dentin complex after direct capping with the new tricalcium silicate–based cement and MTA in human teeth. The null hypothesis was that there wereno differences in the pulp-dentin complex response to 2 capping

materials (Biodentine versus MTA) applied as a direct pulp cap inhuman teeth.

Materials and MethodsOperative Procedure

Twenty-eight intact human caries-free maxillary and mandibularthird molars scheduled for extraction for orthodontic reasons wereselected in 18 patients ranging in age from 19–28 years. Subjects were treated in accordance with the Helsinki declaration. Patientsreceived thorough explanations concerning the experimental rationale,clinical procedures, and possible complications of the procedure. All experimental procedures were reviewed and approved by the Local Ethical Committee, Pomeranian Medical University, Szczecin, Poland

(approval number KB–0012/39/11).Before the operative protocol, each tooth was radiologically examined to exclude the presence of caries or periapical pathology. A standardized operative procedure was followed inboth experimental groups. Thermal testing (K €altespray; M&W Dental GmbH, B€udingen, Germany) and electric sensitivity testing(Vitality Scanner pulp vitality tester; Sybron Endo, Orange, CA) were performed to assess pulp vitality. Before cavity preparation,teeth were mechanically cleaned and disinfected with 0.2% chlo-rhexidine solution. After local anesthesia and rubber dam applica-tion, occlusal Class I cavities were prepared by using round sterilediamond burs at high speed under air-distillated water spray coolant. An exposure of approximately 1.2 mm in diameter wasmade with round carbide burs (4   1.2 mm) under air-distillated water cooling. New burs were used during each oper-ation. Bleeding was controlled with saline irrigation, and a sterilecotton pellet was placed onto the pulp exposure sites.

The teeth were divided into 2 experimental groups, Biodentine(n = 11) or MTA (n = 11), and 1 control group (n = 6). In groupI, pulps of teeth were capped with Biodentine according to the manu-facturer’s recommendations. Biodentine was also used for temporary restoration so that the entire cavity was filled with bioactive cement. Ingroup II, exposed pulps and the surrounding dentin were capped witha 2-mm-thick layer of ProRoot White MTA (Dentsply, Tulsa Dental,Tulsa, OK) according to the manufacturer’s recommendations. Afterplacing the MTA, the operator laid a flat, water-moistened cotton pellet directly over the material and provisionally restored the tooth with

glass ionomer cement (Ketac Molar; 3M ESPE, Seefeld, Germany).Patients in both groups returned to the clinic for clinical examinationsand placement of the final composite restoration after 7 days. Theoperator also verified the setting of MTA. All procedures were per-formed by one experienced operator (A.N.) in the Department of Conservative Dentistry.

Six intact teeth were selected as the control group (group III), which received no exposure and pulp capping.

Clinical ExaminationPatients were also asked about postoperative sensitivity or pain

throughout the study period. Thermal testing and electric sensitivity testing were performed to assess pulp health. Radiographs were taken

before extraction to observe signs of periapical pathology. The length of the treatment period was 6 weeks.

The teeth were extracted as atraumatically as possible by a desig-nated oral surgeon (K.S-T.) in the Department of Dental Surgery.

Histologic Examination After fixation for 2 weeks in 10% buffered formalin solution, the

specimens were demineralized in a decalcifying solution containing

10%nitric acid andwere embedded in paraffin. Two- to 3-micron-thick serial sections in the linguobuccal plane of the paraffin-embedded teeth were stained with hematoxylin-eosin. The Brown and Brenn technique was used to stain bacteria. Presence of stained bacteria was analyzed inthe specimens along the cavity walls, within the cut dentinal tubules andthe dental pulp.

Coded samples were used throughout the study to avoid possiblebias. By using an optical microscope (Carl Zeiss Imager D1 Axio, Goet-tingen, Germany) connected to a high-resolution video camera (AxioCam MRc5; Carl Zeiss Micro imaging, Thornwood, NY), samples were evaluated under normal and ultraviolet light by using 38 HEeGFP and 43 HE Cy 3 filters by an experienced oral pathologist (M.P.).

Theamount of hard tissueformation at theinterface of thecappingmaterial (continuity, morphology, and thickness), pulp inflammation

(type, intensity, and extension), and other histologic features of thepulp tissue including the odontoblast cell layer and bacterial penetra-tion were determined according to the modified criteria by Faracoet al  (14) and Medina et al  (28). Each histomorphologic section wasscoredfrom 1–4, with 1 representing themost desired resultand 4 rep-resenting the least desired result.

For continuity of the dentinal bridge, 1 = complete dentin bridgeformation, 2 = partial/incomplete dentin bridge formation extending tomore than one-half of the exposure site but not completely closing theexposure site, 3 = initial dentin bridge formation extending to not morethan one-half of the exposure site, and 4 = no dentin bridge formation.

For morphology of dentinal bridge, 1 = dentin or dentin associ-ated with irregular hard tissue, 2 = only irregular hard tissue deposi-

tion, 3 = only a thin layer of hard tissue deposition, and 4 = no hardtissue deposition.

For thickness of dentinal bridge, 1 = >0.25 mm, 2 = 0.1–0.25mm, 3 = <0.1 mm, and 4 = partial or absent bridge. The thicknessof dentinal bridge was measured at the thickest, thinnest, and midmost point areas of the continuous dentin bridge. The average of the 3 values was calculated.

For type of pulp inflammation, 1 = no inflammation, 2 = chronicinflammation, 3 = acute and chronic inflammation, and 4 = acuteinflammation.

For intensity of pulp inflammation, 1 = absent or very few inflam-matorycells; 2 = mild, definedas an average of <10inflammatory cells;3 = moderate, definedas an average of 10–25 inflammatory cells;and 4

= severe, defined as an average >25 inflammatory cells.For extensity of pulp inflammation, 1 = absent; 2 = mild, definedas inflammatory cells only next to dentin bridge or area of pulp expo-sure; 3 = moderate, defined as inflammatory cells observed in part of coronal pulp (in one-third or more of the coronal pulp or in the mid-pulp); and 4 = severe, defined as all coronal pulp is infiltrated ornecrotic.

Forodontoblasticlayer, 1 = palisade pattern of cells,2 = presenceof odontoblast cells and odontoblast-like cells, 3 = presence of only odontoblast-like cells, and 4 = absent.

Forbacterial penetration, 1 = absence of stained bacterial profilesin any part of the sections, 2 = presence of stained bacterial profilesalong the coronal or apical walls of the cavity, 3 = presence of stainedbacterial profiles within the cut dentinal tubules or axial wall of the

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cavity, and 4 = presence of stained bacterial profiles within the dental pulp.

Statistical AnalysisThe results of the histopathologic evaluation were statistically 

analyzed by using the Mann-Whitney  U  test. A  P  value <.05 was consid-ered statistically significant.

Results After treatment, 7 patients (4 with Biodentine and 3 with MTA)

complained of spontaneous minor pain, mostly on the day of surgery.Other patients reported no particular symptoms during the experi-mental time period. Before extraction, all teeth were cold-sensitiveand electro-sensitive and had vital pulp. In addition, no periapical pathologies were revealed by radiography before the clinical procedureand extraction.

Histologic evaluation of teeth showed that both materials were well tolerated by the pulp tissue. Results of all the specimens in the Bio-dentine and MTA groups are provided in  Table 1. In the Biodentineexperimental group, the pulp responses were similar to those observed

in the MTA group (Fig. 1, Table 1). The dentin bridge was formeddirectly underneath the capping materials at the injury site with bothmaterials. Complete dentin bridge formation was observed in 6 teethin Biodentine and 7 teeth in the MTA groups (Fig. 1 A, C, and  E ). Inmost specimens in both groups, dentin was associated with an irregularhard tissue, but occasionally the reparative tissue appeared heteroge-neous with cell inclusions. The mean thicknesses of the hard-tissuedentin bridge in the Biodentine and MTA groups were 211.56  mmand 230.31 mm, respectively.

There was no evidence of inflammation, abscess, or necrosisbelow the dentinal bridge (Table 1). An absence of or few inflammatory cells and, rarely, dilated blood vessels were observed in a majority of pulp specimens (Fig. 1). Minimal changes such as concentratedcollagen fibers and congested blood vessels were observed as thedescent of chronic inflammation in 3 teeth in the Biodentine groupand 2 teeth in the MTA group.

In most specimens in both groups, odontoblast and odontoblast-like cells were discovered adjacent to the dentinal bridge with well-distinguishable dentin tubules and with irregular pattern of tubules(Fig. 1 B, D,   and   F ). The layers of well-arranged odontoblast andodontoblast-like cells were found to form tubular dentin under the os-teodentin.

Specimens in the control group exhibited normal pulp tissue withpalisade columnar odontoblast cells, a zone of Weil, a cell-rich zone,and central pulp with normal characteristics.

Regarding the histologic evaluation criteria, our investigationshowed that there was no statistically significant difference betweenthe responses of teeth to Biodentine compared with MTA as a pulp-capping agent ( P  > .05).

DiscussionThis study presents a light microscopic analysis comparing Bio-

dentine with MTA in the pulpal response to direct pulp capping inhealthy human third molars. The findings of our study indicate that iatrogenic pulp defects treated with both calcium silicate cements areessentially free from inflammation and become covered with compact,dentin-like hard tissue bridges. On the other hand, this study presentscomprehensive data on the bridge and pulpal inflammation witha similar outcome of pulp capping with Biodentine and MTA. Thus,the null hypothesis that there are no differences in the pulp-dentincomplex response to the 2 capping techniques (Biodentine andMTA) as a direct pulp capping in human teeth can be accepted.

Handling characteristics are important when considering any material for clinical use. In our study, because of the mechanical prop-erties of Biodentine, this material received good rates for material handling and performance after restoration placement   (3, 4,

22–26). Compared with Biodentine, MTA placement was more time-consuming and technically difficult, although it is necessary to usea dental triturator for preparation of Biodentine. On the other hand,MTA does not require any additional equipment.

Formation of the dentinal bridge at the interface between the pulpand pulp-capping material is a controversial issue because it can bea sign of healing or a reaction to irritation   (12, 16, 29). In thepresent study, formation of the dentinal bridge was interpreted asa positive reaction to stimulation and a sign of healing. Both materialsinduced the formation of a dentinal bridge at its interface with thepulp tissue columnar cells, with polarized nuclei projecting intoinvaginations of the bridge observed in some specimens, which isclearly indicative of the formation of odontoblast cells and initiation of 

tubular dentin (Fig. 1). Both calcium silicate cements induced an early form of reparative dentin synthesis, probably because of modulation of pulp cell transforming growth factor–b1 secretion (3, 4, 26). Laurent etal (3) showed thatparticles of Biodentine wereentrapped in the newly formed foci, andmineralizationappeared as osteodentin, suggesting that material physicochemical properties might promote the mineralizationprocess as shown with MTA-based cements. Stimulation of cell prolifer-ation and differentiation might be related to the tricalcium silicate itself, which is one of the main components of Biodentine, and the presenceof both calciumandsiliconions (3,4, 25–27). However, additionalstudiesare needed with immunohistochemistry and transmission electronmicroscopy to assess the mode of action of Biodentine on the pulp.

Clinical criterion is inadequate for the long-term prognosis

because critical evaluation of the results of pulp-capping materialscan only be made histologically   (1, 16). Numerous investigationshave reported the successful application of MTA in pulp capping(1, 2, 6, 10–16, 19, 26). In the present study, dentin bridgeformation was observed in all pulps capped with MTA as previously observed   (2, 10, 16, 26). Researchers evaluated a combination of CaCl 2 and MTA as a pulpotomy agent and described favorable resultsin calcified bridge formation (19), which was in accordance with theresults of the current investigation. However, Parirokh et al  (1) re-ported that adding CaCl 2 to MTA pulp-capping agent did not improvethe properties of this biomaterial. In contrast to our study, histologicresults showed higher percentages of inflammation and necrosis anda lower percentage of calcified bridge formation in MTA/CaCl 2 samplescompared with MTA.

TABLE 1.   Summary of Different Categories of Histologic Features of Biodentineand MTA According to the Scores

Biodentine MTA

1 2 3 4 1 2 3 4

Hard tissue bridgeContinuity 6 5 0 0 7 4 0 0Morphology 7 3 1 0 7 2 2 0Thickness 4 4 3 0 5 3 3 0

Evaluations of inflammatory responseType 8 3 0 0 9 2 0 0Intensity 8 3 0 0 9 2 0 0Extension 8 2 1 0 9 1 1 0

Odontoblastic layer 2 6 3 0 2 7 2 0Presence of microorganisms 11 0 0 0 11 0 0 0

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The new tricalcium silicate–based cement was tested in vivo inanimals by Tran et al  (26). This study evaluated the capacity of Bio-dentine, MTA, and Ca(OH)2 to induce pulp healing in a rat pulp injury model. Similar to our study, the researchers observed formation of a dentin bridge at the injury site after 30 days that was secreted by cellsdisplaying an odontoblastic phenotype in all evaluated materials. Thesereparative structures thatwereinducedby bothcalciumsilicate cements were homogenous and in continuity with primary dentin. In contrast,the reparative tissue induced by calcium hydroxide had a porous orga-

nization, suggesting a reparative process different from those inducedby calcium silicate cements. Similar to our observations, dentin tubulescould be clearly observed, and the cells secreting this structuredisplayed odontoblastic characteristics (26).

Studies report that pulp response after direct capping is linked tobacterial microleakage (6, 10, 12–15, 17). Microbes interfere with thepulpal response to capping materials   (11, 30). It was noted that bacteria stimulate pulpal inflammatory activity and reduce the area of dentin bridge formation irrespective of the material used for pulpcapping (31). Many authors have suggested that pulpal survival afteran oral exposure is not so much a function of an agent’s potential bioac-tivity but itscapacityto protect thepulp from bacterialexposures (9,11,12, 32–34). Prevention of bacterial leakage into cavity preparations isan important objective in treatment planning and contributes to the

longevity of cavity restorations (31). In the present study, an absenceof bacteria in the stains may indicate that Biodentine and MTA haveexcellent sealing properties and prevent microleakage and pulpal inflammation by providing a predictable secondary barrier under thesurface seal. Moreover, all the cavities in our study were surface-sealed with resin composite to prevent microbial leakage. The clinical trial evaluating the performance and safety of the new cement  (22) re-ported that Biodentine may be successfully used as a posterior restora-tion material for up to 6 months after direct pulp capping. After

 validation of pulp health, it may be partially removed to place a perma-nent composite material  (22, 23).In our study the teeth had no inflammation process. Direct pulp

capping is used not only for accidental exposures of healthy pulpsbutalsofor pulpschallengedby cariesor oral exposure after a traumaticinjury. Therefore, the relevance of these studies conducted in healthy human teethmay be clinically limited,and further long-term assessment is required to evaluate the pulp response to Biodentine in inflamedpulp.

Conclusion Within the limitations of this study, Biodentine had a similar

efficacy in the clinical setting and may be considered an interestingalternative to MTA in pulp-capping treatment during vital pulp therapy.

Figure 1.  Human pulp capped with Biodentine ( A, B, C, and  D) and MTA ( E  and  F ). ( A and  C ) The complete dentin bridge formation with Biodentine. Dentinbridge incorporating dentin chips (*), (hematoxylin-eosin; original magnification,50). ( B  and D) Higher magnification of ( A and C ). Observe hard bridge tissue,

new odontoblast cell layer, and dentinal tubules ( arrow) (hematoxylin-eosin; original magnification,

400). ( E ) The complete dentin bridge formation with MTA.( F ) Higher magnification of ( E ). Observe hard bridge tissue, new odontoblast cell layer, and dentinal tubules ( arrow) (hematoxylin-eosin; original magnification,400). B, Biodentine; D, dentin; DB, dentin bridge; M, MTA; OL, odontoblast layer; P, pulp.

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 Acknowledgments

The authors deny any conflicts of interest related to this study.

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