Published online: 2020-07-29

THIEME
Review Article 1

Mineral Trioxide Aggregate Applications in

Endodontics: A Review
Gabriele Cervino1,    Luigi Laino2,1  Cesare D’Amico1  Diana Russo2  Ludovica Nucci2  Giulia Amoroso1 
Francesca Gorassini1  Michele Tepedino3  Antonella Terranova1  Dario Gambino1 
Roberta Mastroieni1  Melek Didem Tözüm4  Luca Fiorillo1

1 Department of Biomedical, Dental, Morphological and Address for correspondence Luca Fiorillo, DDS, PhD, Department
Functional Imaging Sciences, University of Messina, of Biomedical, Dental, Morphological and Functional Imaging
Policlinico G. Martino, Messina, Italy Sciences, University of Messina, Policlinico G. Martino,
2 Multidisciplinary Department of Medical-Surgical and Via Consolare Valeria 1, 98100 Messina, Italy
Dental Specialties, Second University of Naples, Naples, Italy (e-mail: [email protected]).
3 Fondazione Policlinico Universitario A. Gemelli IRCCS,
Istituto di Clinica Odontoiatrica e Chirurgia Maxillo-Facciale,
Roma-Università Cattolica del Sacro Cuore, Rome, Italy
4 Pre-Doctoral Clinics, College of Dentistry, University of Illinois
at Chicago, Chicago, Illinois, United States

 Eur J Dent

Abstract A current topic in dentistry concerns the biocompatibility of the materials, and in par-
ticular, conservative dentistry and endodontics ones. The mineral trioxide aggregate
(MTA) is a dental material with biocompatibility properties to oral and dental tissues.
MTA was developed for dental root repair in endodontic treatment and it is formu-
lated from commercial Portland cement, combined with bismuth oxide powder for
radiopacity. MTA is used for creating apical plugs during apexification, repairing root
perforations during root canal therapy, treating internal root resorption, and pulp cap-
Keywords ping. The objective of this article is to investigate MTA features from a clinical point of
►►dental materials view, even compared with other biomaterials. All the clinical data regarding this dental
►►Portland cements material will be evaluated in this review article. Data obtained from the analysis of the
►►dentin past 10 years’ literature highlighted 19 articles in which the MTA clinical aspects could
►►pulp exposure be recorded. The results obtained in this article are an important step to demonstrate
►►pulp capping the safety and predictability of oral rehabilitations with these biomaterials and to pro-
►►root canal filling mote a line to improve their properties in the future.

Introduction In the past 10 years, the MTA found its application in the
field of dentistry with specific fit within the conservative
The mineral trioxide aggregate (MTA) is a hydrophilic and bio- and endodontic treatments. A dental trauma is an event that
compatible endodontic cement, capable of stimulating healing cannot be predicted and usually it is not easy for the clini-
and osteogenesis. It consists of a powder of fine trioxides (trical- cians to manage it. The dentist should therefore be prepared
cium oxide, silicon oxide, bismuth oxide) and other hydrophilic to intervene in patient who has suffered a dental trauma.
particles (tricalcium silicate, tricalcium aluminate, responsible Early intervention is often crucial to improve the prognosis
for the chemical and physical properties of this aggregate), of the trauma itself. In the presence of a coronal fracture with
which hardens in the presence of humidity.1-5 The hydration of dentine exposure, the primary objective should be to seal
the powder results in the formation of a colloidal gel with pH dentinal tubules. Especially in a young patient, the size and
12.5, which solidifies in a structure in about 3 to 4 hours.6-9

DOI https://doi.org/ ©2020 Dental Investigation

10.1055/s-0040-1713073 Society
ISSN 1305-7456.
2 A Review on Clinical Applications of MTA  Cervino et al.

number of dentinal tubules are large: even a small amount Materials and Methods
of exposed dentin therefore allows a large number of plaque
bacteria and their metabolites to move to the underlying pulp Protocol and Registration
and cause inflammation. An occurrence of this type could, This article has been registered as review in a systemic review
sometimes in short time, lead to necrosis. When the dental database called PROSPERO. It is an International Prospective
trauma has caused a pulp exposure, the emergency interven- Register of Systematic Reviews about health and social
tion consists with the management of the exposed pulp. One care. Obtained PROSPERO registration number is 156248
of the treatments, besides the endodontic treatment, is direct on October 27, 2019. The main question of this study has
capping or partial pulpotomy. Partial pulpotomy could be been elaborated following PICOT (Population/Intervention/
performed using MTA. The MTA could be applied as cement Comparison/Outcome/Time) study design.
for its high compatibility, which has a mechanism similar to This review follows a protocol according to PROSPERO and
calcium hydroxide (Ca (OH)2) (extremely basic) and therefore Preferred Reporting Items for Systematic Reviews and Meta-
a powerful antibacterial. Analyses (PRISMA) (Transparent Reporting of Systematic
Unlike Ca(OH)2, however, the MTA hardens, reaching a Reviews and Meta-Analyses).
good consistency; it is, therefore, extremely suitable for any
restoration. Fast hardening therefore allows partial pulpo- Eligibility Criteria
tomies performed with MTA to be restored in a definitive The results obtained from the literature search were filtered,
manner.7 through software and manual screening, according to the fol-
Pulp consisting of a cellular component, vessels and lowing inclusion and exclusion criteria:
nerves; this tissue is called mature mucosal connective • Inclusion criteria
tissue. Endodontic therapy is used if a tooth carious or ◦◦ Human studies
traumatic injury has caused an irreversible alteration of ◦◦ Information about MTA clinical use
the pulp tissue and its necrosis. It is also possible to use ◦◦ Information about MTA and other biomaterials in
this method if the dental element is to be involved in endodontics
prosthetic rehabilitations, which due to the considerable ◦◦ In vitro and in vivo studies about MTA
reduction of the dental tissue, it would determine, with ◦◦ Last 10 years of studies
high probability, an irreversible pulp alteration. During
endodontic treatment, blood contamination should be • Exclusion criteria
absolutely avoided, and the roots canal system needs to be ◦◦ In silica studies
dry, to obtain a successful root canal filling. During direct ◦◦ Not on human studies
pulp capping or perforation sealing, it is fundamental to ◦◦ Not in English
control the bleeding and obtain a dry field too. The mech- ◦◦ Not accessible title or abstract
anism of action of the MTA is related with the clinical fea- ◦◦ Not enough information about main question
tures of the human oral cavity. MTA, when placed in direct
contact with human tissues, is able to release calcium ions
for cell proliferation. Moreover, it creates an antibacterial Information Sources
environment by its alkaline pH, regulating the cytokine Results were obtained after a research and a screening on sci-
production. Therefore, it favors the migration and differ- entific international database as PubMed, Embase, and Web
entiation of hard tissue producing cells forming hydroxy- of Science. Automatic filter and platforms software have been
apatite on MTA surface and providing a biological seal. used for results screening.
Finally, during a surgical endodontic procedure, the retro-
grade cavity should be completely dry. This cement differs Search
from all other materials currently in existence, thanks to Search has been conducted using this keyword on informa-
its biocompatibility, its antibacterial properties, its mar- tion sources: “Mineral Trioxide Aggregate.” Search date is
ginal adaptation, and its sealing capacities, and finally, August 1, 2019.
thanks to its hydrophilic nature. It is important to under- The database search protocol details are: (“mineral tri-
stand the functioning of this biomaterial, its behavior with oxide aggregate”[Supplementary Concept] OR “mineral
contact with other materials used in dentistry, and above trioxide aggregate”[All Fields]) AND (“2009/10/30”[PDat]:
all, over time or from a clinical and radiographic point of “2019/10/27”[PDat] AND “humans”[MeSH Terms]).
view.10-12 Investigating these topics requires a research into Keywords have been chosen by authors after a discussion
the international literature, which also includes the use of with the aim to include as large as possible number of results
cutting-edge technologies for examination.13-16 (►Fig. 1).
The purpose of this review is to evaluate all the recent PICO questions are:
scientific literature concerning this topic and to evaluate all • In dental patients, what is the effect of MTA use on pulp
its clinical features. The evaluation of different studies offers vitality?
information about the facets of the material related to end- •• How MTA features could improve clinical success on den-
odontics, conservative dentistry, and oral surgery. tal patients?

European Journal of Dentistry

 A Review on Clinical Applications of MTA  Cervino et al. 3

Summary Measures
Summary measures are shown in ►Table 1.

Synthesis of Results
The authors performed the summary of the results manually,
after reading the title, abstract, and full text of each article.

Risk of Bias
A risk of bias evaluation was performed according to Higgins
et al. Risk of bias has been conducted to improve review qual-
ity according to PRISMA statement too.17-20

Results
Study Selection
The results were obtained in relation to the “Materials
and Methods” instructions. Using the set out in paragraph
2.4 keywords, 2,595 results were obtained. Subsequently,
according to eligibility criteria, results have been screened.
The authors decided to maintain only past 10 years results to
underline the novelty and accuracy on diagnostics method as
Fig. 1 Preferred reporting items for systematic reviews and well as the quality of the new technologies results in the field
meta-analyses flow chart.
of MTA application. A total of 1,931 results remained after
this first screening. Only 25 studies on human have been con-
Study Selection sidered, and the authors analyzed full text and English arti-
Authors with the aim to include relevant studies for this cles. The last step to complete the revision of the results was
review have conducted selection process. After applying the to compare only review articles type. Only 19 results, after a
electronic eligibility criteria, the authors conducted a manual reading and a manual authors screening, were resulted eligi-
study selection independently. ble for this study (►Fig. 1).

Data Collection Process Results of Individual Studies

Two independent authors from two different universities Results of individual studies are listed in ►Table  2 and
conducted the data collection process (D.R., University of ►Fig. 2. The results are divided accordingly to PRISMA state-
Naples and L.F., University of Messina). After data screen- ment and organized into sample, items, outcomes, and type
ing completion, they clarified any doubt with other expert of study. Authors’ name and year have been restricted follow-
reviewers (M.D.T. and L.L.). ing the interval time range of 10 years.

Data Items Synthesis of Results

The following data items were considered during data col- Çelik et al20 analyzed differences between two groups of
lection; summary measures and data items are shown in patients involved in pulpotomy treatment. The MTA groups
►Tables 1 and 2: had a 100% success rate at 24 months instead of 89.4% with
• Investigated data items on articles (►Table 2) Biodentine use. According to Erfanparast et al,21 there are no
significant differences on resin-modified Portland cement-
◦◦ Authors and year—article authors and year of publication
based materials versus MTA in direct pulp capping. After
(references have been added)w
12 months, the success rate for MTA and resin-modified one
◦◦ Sample—sample size and groups size
were 94.5 and 91.8%, respectively. Koc Vural et al22 evaluated
◦◦ Outcome—main results of the study
differences between Ca(OH)2 and MTA. The follow-up term
◦◦ Type of study—type of article.
for a total of 100 samples was of 24 months. Four Ca(OH)2
capped teeth and two MTA capped received endodontic
Table 1  All mineral trioxide aggregate use emergency treatments. But there are no significant differ-
Conservative dentistry Indirect pulp capping
ences between groups. Kang et al23 studied clinical differ-
ences between three MTA groups (ProRoot MTA, Ortho MTA,
Direct pulp capping
and RetroMTA). The success rate at 1 year was high with no
Endodontic dentistry Root filling significant differences; the success rates were 96, 92.8, and
Root filling with postcore 96%, respectively (as listed in parentheses). Bakhtiar et al24
indication
investigated differences on third molar pulpotomy between

European Journal of Dentistry

4 A Review on Clinical Applications of MTA  Cervino et al.

Table 2    Main results and item investigated on reviews

Authors (y) Sample Items Outcomes Type of study
Çelik et al (2019) 20
24 + 20 MTA vs. Biodentine Differences on success, RCT
p = 0.646
Erfanparast et al 46 × 2 (split mouth) Resin modified Portland Differences are not signifi- RCT
(2018)21 cement vs. MTA cant, p > 0.05
Koc Vural et al 49 + 51 MTA vs. calcium hydroxide There are no differences RCT
(2017)22 between used materi-
als, p = 0.238 (or higher)
Kang et al (2017)23 33 + 36 + 35 ProRoot MTA vs. Ortho MTA No significant differences RCT
vs. RetroMTA between groups
Bakhtiar et al 9 + 9 + 9 TheraCal vs. Biodentine vs. Normal pulp organization RCT
(2017)24 ProRoot MTA (p = 0.06); dentinal bridge
formation (p = 0.001)
Asl Aminabadi et al 40 + 40 + 40 + 40 Simvastatin vs. 3Mix vs. No differences between RCT
(2016)25 3Mixtatin vs. MTA MTA and 3Mixtatin
(p > 0.05)
Aminabadi et al 40 + 40 3Mixtatin vs. MTA Clinical differences RCT
(2016)26 between groups
Nowicka et al 11 + 11 + 11 + 11 Calcium hydroxide, MTA, Reparative formed dentin RCT
(2015)27 Biodentine, Single Bond was less in Single Bond
Universal Universal group; the mean
density of dentin bridges
was the highest in the MTA
group and the lowest in
the Single Bond Universal
group
Kang et al (2015)28 49 + 47 + 47 RetroMTA vs. Ortho MTA vs. Clinical success rate is RCT
PRoRoot MTA similar and not statistically
significant
Bonte et al 15 + 15 MTA vs. calcium hydroxide Success rate demonstrated RCT
(2015)29 a difference between
groups, p < 0.7
Petrou et al 31 + 26 + 29 Calcium hydroxide vs. medi- Difference between RCT
(2014)30 cal Portland cement vs. white groups are not significant
MTA (p = 0.72)
Hilton et al 181 + 195 Calcium hydroxide vs. MTA Failure rate at 24 mo was RCT
(2013)31 31.5% for calcium hydrox-
ide and 19.7% for MTA
Gandolfi et al 8 + 8 AH Plus vs. MTA Flow MTA flow sealer created a RCT
(2013)32 dense apatite layer after
7d
Bernabé et al 34 ProRoot MTA Sonic vibration could be RCT
(2013)33 considered an efficient aid
to improve MTA sealing
ability

Sönmez et al 15 + 15 + 15 + 6 AH Plus vs. MTA Fillapex vs. MTA Fillapex had higher RCT
(2012)34 ProRoot MTA vs. control microleakage values,
p < 0.05
Leye Benoist et al 60 MTA vs. calcium hydroxide Success rates are different RCT
(2012)35 between groups at 3 mo,
p = 0.02
Ghoddusi et al MTA vs. ZOE) MTA and ZOE showed both RCT
(2012)36 clinical success
Hansen et al 12 + 12 ProRoot MTA vs. pH level was RCT
(2011)37 EndoSequence Root Repair higher for MTA and
Material EndoSequence p < 0.05
Yildirim et al 15 + 15 + 15 + 6 Gutta-percha vs. Gutta- MTA showed less microle- RCT
(2009)38 percha prepared with gates akage, p < 0.005
vs. MTA vs. control
Abbreviations: MTA, mineral trioxide aggregate; RCT, randomized controlled trial; ZOE, zinc oxide eugenol.

European Journal of Dentistry

 A Review on Clinical Applications of MTA  Cervino et al. 5

versus white MTA did not show any statistical difference. The
total success rate was 90.3%. Hilton et al31 recently published
a study about the clinical and radiographic differences on
two direct capping materials groups, Ca (OH)2 versus MTA.
MTA showed a less failure rate (p = 0.046). Gandolfi et al32
analyzed, through a three-dimensional microcomputed
tomography (3D micro-CT) analysis, differences between
AH Plus and MTA flow on their microstructure. Bernabé
et al33 tested the MTA sealing ability for apicectomy. They
filled with MTA plus sonic, ultrasonic, or no vibration. The
sonic vibration could improve sealing level. Sönmez et al34
showed differences on the apical microleakage between
AH Plus, MTA Fillapex, and ProRoot MTA. Fillapex had bet-
ter results about microleakage and there are no statistical
differences between AH Plus and MTA. Leye Benoist et al35
highlighted differences between Ca (OH)2 and MTA for indi-
rect pulp capping. At 3 months, the success rate of MTA
was 93% instead of 73% for Ca (OH)2. At 6 months, the suc-
Fig. 2  Success rate frequency polygon chart of MTA (blue) versus
cess rate was 89.6% for MTA instead of 73%. The mean initial
other biomaterials. MTA, mineral trioxide aggregate.
residual dentine thickness was 0.23 mm, this value has been
increased to 0.121 mm with MTA and 0.136 with Ca (OH)2
three different materials (TheraCal, Biodentine, and ProRoot). at 3-month time. According to Ghoddusi et al,36 there are no
They showed how there were no clinical signs on ProRoot statistical differences between MTA or zinc oxide eugenol
MTA and Biodentine groups as two patients reported signif- (ZOE) in pulpotomy after a carious or traumatic pulp expo-
icant pain in TheraCal group. Pulp reorganization was seen sure. Hansen et al37 considered the pH level with the use of
in 33.33% of ProRoot MTA, 11.11% of TheraCal, and 66.67% different biomaterials for pulp capping. The authors stud-
of Biodentine groups. Moreover, dentinal bridge formation ied MTA, Endodontic Sealing(ES); control pairs were filled
was seen on 11% of TheraCal and 56% of ProRoot MTA. Asl with Ca (OH)2 (positive group) and saline (negative). The pH
Aminabadi et al25 tested clinical differences between four was measured at 20 minutes, 3 hours, 24 hours, and 1–2 to
groups for direct pulp capping. Noncaries pulpal exposures 3–4 weeks. The MTA pH was significantly higher during the
were treated with simvastatin, 3Mix, 3Mixtatin, or MTA. At time than ES (at 1 week, p < 0.0001). Yildirim et al38 discov-
the end of a 12-month follow-up period, the overall success ered differences on filling between gutta-percha with two
rates were 93.8% (MTA), 91.9% (3Mixtatin), 62.5% (3Mix), and methods and MTA. Cervino et al obtained better results with
57.1% (simvastatin). According to the authors, there were no MTA, then showed less microleakage (►Fig. 3).7
significant differences (p = 0.05) between MTA and 3Mixtatin
groups. 3Mixtatin groups had a statistical difference on
simvastatin and 3Mix groups (p < 0.01). Another study of
Discussion
Aminabadi et al26 confirmed 3Mixtatin efficiency on pulp All the conclusions of the selected articles for this present
capping. The authors inspected MTA versus 3Mixtatin on review have been summarized in this section as follows:
direct pulp capping with a 96.8% of success rate against MTA Çelik et al20 evaluated clinical success differences between
with 48.6% of referred pain. Nowicka et al27 evaluated differ- MTA and Biodentine. The authors showed how both MTA and
ences on direct pulp capping between four groups: Ca (OH)2, Biodentine are appropriate options for pulpotomy. According
MTA, Biodentine, and Single Bond Universal. The reparative to this study, it seems how the etiology of pulp exposure
dentin formed in the Ca (OH)2, MTA, and Biodentine was is the crucial on pulpal response (mechanical or carious)
superior to the Single Bond Universal group. Moreover, the whether or not the kind of material applied. Erfanparast
dentin bridges density was the highest in the MTA group and et al21 concluded that resin-based Portland cement results
the lowest in the Single Bond Universal group. Kang et al28 are comparable to MTA for primary molars after 12 months
published a report about differences on three MTA mate- of follow-up and no significant differences can be under-
rials. At 12 months, the radiographic success rates in these lined between the two biomaterials investigated. Koc Vural
groups were 100% (RetroMTA), 97.4% (Ortho MTA), and 100% et al performed a similar study, about the comparison of two
(ProRoot MTA). The Kaplan–Meier’s survival function rela- endodontic materials.22 The authors reported that Ca (OH)2
tive to clinical and radiographic rates did not differ between and MTA are both accepting pulp-capping materials at a
groups. According to Bonte et al,29 MTA at 12 months pro- 24-month follow-up term.
duced mineralized barrier in 82.4% of cases instead of Ca Kang et al23 in a 1-year follow-up study investigated three
(OH)2 (50%). Pain and tenderness to percussion had disap- different materials applied to pulpotomy technique. The pro-
peared in both groups. In a Petrou et al30 randomized con- cedure was classified as safe and predictable with ProRoot
trolled trial, it was demonstrated at ~6.3 months of time on MTA, Ortho MTA, or RetroMTA documented through clini-
86 patients how Ca (OH)2 versus medical Portland cement cal and radiographical data. Bakhtiar et al24 published an in

European Journal of Dentistry

6 A Review on Clinical Applications of MTA  Cervino et al.

to Ca (OH)2. Gandolfi et al32 concluded in their study, after a

3D micro-CT analysis, that MTA flow created an apatite layer
after 7 days, and AH Plus even after 28 days. Bernabé et al33
showed how MTA could be useful item for root canal filling
after apicectomy; moreover, a sonic vibration could improve
sealing ability. Sönmez et al34 concluded that the sealing abil-
ity of AH Plus and ProRoot is similar, but MTA Fillapex showed
microleakage compared with the other two materials.
Some studies reported how the results could be modified
if the evaluation is reported at 3, 6 months, or 1 year after
the treatment. This clinical condition demonstrated how the
patient response could be individual and not related to the
materials or technique applied. According to Leye Benoist
et al,35 a higher success rate was observed in the MTA group
instead of Ca (OH)2. Differences were significant at 3 months
but not at 6 months, with no dentine thickness differences,
showing time of evaluation importance. Ghoddusi et al36 con-
cluded that there are no statistical differences between ZOE
or MTA treatments, but MTA was successful, expensive, and
because of dentin bridges could complicate future root canal
therapy. Data reported by Hansen et al37 demonstrated how
Fig. 3 SEM microleakage between MTA and bonding agents. The the MTA produce an intracanal higher pH than ES. The same
MTA use could, in some cases, make the definitive reconstruction result was demonstrated by Yildirim et al.38 MTA can be used
complex due to the physical–chemical properties of itself and dif- in the root canals as apical filling materials, in particular, in
ficulty of use with hydrophobic substances. MTA, mineral trioxide teeth with postcore indication.
aggregate; SEM, scanning electron microscope.
All these results extrapolated by the selected articles
provide us documented clinical information and the MTA
vitro study about how some endodontic biomaterials could seems to be as having excellent abilities from the point of
be efficient than others for the pulp capping procedures. view of biocompatibility, as could be seen from the stud-
The authors performed histology to evaluate dentinal bridge ies, but also of stability over time.39-41 The nanocharac-
formation and organization after teeth extraction (disodon- teristic of the MTA could be related about its interactions
tiasis third molar). Data demonstrated how Biodentine and with the human tissue during the endodontic treatment.
ProRoot MTA work better than TheraCal. Remineralizing potential intercepting early lesion progres-
According to Asl Aminabadi et al,25 there are no radio- sion as nanosized calcium phosphate, carbonate hydroxy-
graphic and clinical differences between MTA and 3Mixtatin, apatite nanocrystals, nanoamorphous calcium phosphate,
and it could represent a valid alternative in direct pulp cap- and nanoparticulate bioactive glass particularly with pro-
ping. Aminabadi et al26 evaluated at 24 months the efficiency vision of self-assembles protein that furnish essential role
of 3Mixtatin, showing how this biomaterial could have bet- in biomimetic repair even in the dental field. The unique
ter clinical result than MTA from a clinical and radiographic size of nanomaterials makes them fascinating carriers for
point of view. According to the authors, it could represent the dental products.42-50 Thus, it is recently claimed that forti-
future pulp capping material. fying the adhesives with nanomaterials that possess bio-
Several published articles underlined the clinical features logical merits does not only enhance the mechanical and
of the MTA just evaluating clinical and radiological data. physical properties of the adhesives but also help attain
Nowicka et al27 demonstrated how the reparative dentin and maintain a durable adhesive joint and enhanced lon-
bridges are dependent on the material used. Biodentine and gevity. It is also necessary to report how these conser-
MTA resulted in the highest volumes after the cone beam vative therapies often do not expose patients to invasive
radiography. According to Kang et al,28 RetroMTA, Ortho MTA, surgical or not risks, practices that in patients with unfa-
and ProRoot MTA success rates did not differ and are indis- vorable systemic conditions would be complex to apply.
tinguishable, and these results indicate that pulpotomy could Accordingly, this review will focus on the current status
be performed with a high success rate with all the evaluated and the future implications of nanotechnology in preven-
biomaterials. Bonte et al29 showed how there is no statistical tive and adhesive dentistry. In dental materials, the main
difference between Ca (OH)2 and MTA, but MTA produced applications of nanotechnology have been to achieve bet-
a better dentin healing, apexification using MTA could give ter mechanical properties, higher abrasion resistance, less
better results than Ca (OH)2. shrinkage, improved optical, and esthetic properties, and
Petrou et al30 concluded that MTA or medical Portland to provide antimicrobial properties. Antimicrobial activity
cements are preferable to Ca (OH)2 for indirect pulp capping is an important property for nanomaterials used in den-
because those materials are nonresorbable materials. Hilton tistry because of the lack of this property in resin-based
et al31 showed how MTA is superior for direct pulp capping materials. MTA is a biomaterial that has numerous

European Journal of Dentistry

 A Review on Clinical Applications of MTA  Cervino et al. 7

possibilities for endodontic therapy, as animal studies 2 Serin Kalay T. Effects of intracoronal bleaching agents on the
and clinical results are highly encouraging. It can also be surface properties of mineral trioxide aggregate. Odontology
2019;107(4):465–472
used in deciduous dentition, with deep carious lesion or
3 Lopes MB, Soares VCG, Fagundes FHR, et al. Analysis of molec-
exposure to the traumatic pulp intended for endodontic ular changes induced by mineral trioxide aggregate on sPLA2.
therapy.51-61 The MTA could not be used to save all teeth Braz Dent J 2019;30(5):453–458
with pulp involvement; however, with a meticulous tech- 4 Liu Y, Liu XM, Bi J, et al. Cell migration and osteo/odontogene-
nique, it could serve as a pulp drug in advance to add to a sis stimulation of iRoot FS as a potential apical barrier material
clinical use. Modern nanotechnology is used in the pro- in apexification. Int Endod J 2020;53(4):467–477
5 Lin YT, Lin YJ. Success rates of mineral trioxide aggregate, fer-
duction of a variety of dental materials such as light-cured
ric sulfate, and sodium hypochlorite pulpotomies: a prospec-
composite resins, adhesive systems, impression materials, tive 24-month study. J Formos Med Assoc 2019
ceramics, dental implant coatings, and bioceramics, among 6 Lapinska B, Klimek L, Sokolowski J, Lukomska-Szymanska
others. In pediatric age, a whole series of dental malocclu- M. Dentine surface morphology after chlorhexidine applica-
sions could occur. There could be different types of dental tion-SEM study. Polymers (Basel) 2018;10(8):905
malocclusions: some are genetic, and others are caused 7 Cervino G, Fiorillo L, Spagnuolo G, et al. Interface between MTA
and dental bonding agents: scanning electron microscope
by external factors; the big difference in the treatment of
evaluation. J Int Soc Prev Community Dent 2017;7(1):64–68
these malocclusions in pediatric and in adulthood is that 8 Lo Giudice G, Cutroneo G, Centofanti A, et al. Dentin mor-
in children, treatment tends to be much less invasive as the phology of root canal surface: a quantitative evaluation based
bones have yet to fully develop and it is easier to intervene on a scanning electronic microscopy study. BioMed Res Int
to correct their shape. Therefore, it should be understood 2015;2015:164065
9 Zarra T, Lambrianidis T, Vasiliadis L, Gogos C. Effect of curing
how the absence of a dental element, extracted rather
conditions on physical and chemical properties of MTA. Int
than saved, thanks to an endodontic treatment, even in Endod J 2018;51(11):1279–1291
borderline conditions, thanks to the use of these cements, 10 Colombo M, Poggio C, Dagna A, et al. Biological and physi-
could have repercussions on the whole stomatognathic co-chemical properties of new root canal sealers. J Clin Exp
system.62,63 Moreover, the material is versatile, guarantee- Dent 2018;10(2):e120–e126
ing different uses, and having excellent characteristics in 11 Lo Giudice G, Cicciù M, Cervino G, Lizio A, Visco AM. Flowable
resin and marginal gap on tooth third medial cavity involving
being in contact with the materials for reconstruction.64-77
enamel and radicular cementum: a SEM evaluation of two res-
toration techniques. Indian J Dent Res 2012;23(6):763–769
Conclusion 12 Fiorillo L, Cervino G, Herford AS, et al. Interferon crevicular
fluid profile and correlation with periodontal disease and
The results of this review would be certainly useful to fully wound healing: a systemic review of recent data. Int J Mol Sci
understand the characteristics and advantages of this bio- 2018;19(7):E1908
material from a clinical point of view; our structural anal- 13 De Stefano R. Psychological factors in dental patient care:
ysis of the material explains its clinical behavior; and the odontophobia. Medicina (Kaunas) 2019;55(10):678
14 Cicciù M, Fiorillo L, Cervino G. Chitosan use in dentistry:
studies examined are the proof. The numerous clinical,
a systematic review of recent clinical studies. Mar Drugs
histological, and radiographic tests make this material a 2019;17(7):417
safe and predictable material in the endodontic and con- 15 Savovic J, Turner RM, Mawdsley D, et al. Association between
servative dentistry fields. Some studies have shown better risk-of-bias assessments and results of randomized trials in
characteristics than the MTA, above all, from an antibi- Cochrane reviews: the ROBES meta-epidemiologic study. Am
J Epidemiol 2018;187(5):1113–1122
otic point of view. This could act as a starting point for
16 Mansournia MA, Higgins JP, Sterne JA, Hernán MA. Biases in
the improvement of this material and the creation of even
randomized trials: a conversation between trialists and epide-
better materials. miologists. Epidemiology 2017;28(1):54–59
Authors’ Contributions 17 Higgins JP, Altman DG, Gøtzsche PC, et al; Cochrane Bias
Methods GroupCochrane Statistical Methods Group. The
Conceptualization, methodology, validation, formal anal-
Cochrane collaboration’s tool for assessing risk of bias in ran-
ysis, investigation, resources, data curation, original draft domised trials. BMJ 2011;343:d5928
preparation, and review and editing of the manuscript 18 Coburn KM, Vevea JL. Publication bias as a function of study
were done by G.C., M.D.T., and L.F.; visualization was per- characteristics. Psychol Methods 2015;20(3):310–330
formed by D.R., L.N., and C.D.A.; data were curated by G.A., 19 Bachelet VC, Pardo-Hernandez H. Quality of reporting and risk
M.T., F.G. and A.T.; L.L. supervised the entire work and L.F. of bias of randomized clinical trials published in Spanish and
Latin American journals. Medwave 2019;19(1):e7573
performed project administration.
20 Çelik BN, Mutluay MS, Arıkan V, Sarı Ş. The evaluation
Funding of MTA and Biodentine as a pulpotomy materials for
carious exposures in primary teeth. Clin Oral Investig
None.
2019;23(2):661–666
Conflict of Interest 21 Erfanparast L, Iranparvar P, Vafaei A. Direct pulp capping in
None declared. primary molars using a resin-modified Portland cement-
based material (TheraCal) compared to MTA with 12-month
References follow-up: a randomised clinical trial. Eur Arch Paediatr Dent
2018;19(3):197–203
1 Tu MG, Sun KT, Wang TH, et al. Effects of mineral trioxide aggre- 22 Koc Vural U, Kiremitci A, Gokalp S. Randomized clinical trial to
gate and bioceramics on macrophage differentiation and polar- evaluate MTA indirect pulp capping in deep caries lesions after
ization in vitro. J Formos Med Assoc 2019;118(10):1458–1465 24-months. Oper Dent 2017;42(5):470–477
European Journal of Dentistry
8 A Review on Clinical Applications of MTA  Cervino et al.

23 Kang CM, Sun Y, Song JS, et al. A randomized controlled trial potential use as biocement. Dig J Nanomater Biostructures
of various MTA materials for partial pulpotomy in permanent 2012;7(4):1639–1646
teeth. J Dent 2017;60:8–13 41 Tao O, Wu DT, Pham HM, Pandey N, Tran SD. Nanomaterials
24 Bakhtiar H, Nekoofar MH, Aminishakib P, et al. Human pulp in craniofacial tissue regeneration: a review. Appl Sci
responses to partial pulpotomy treatment with TheraCal as 2019;9(2):317
compared with Biodentine and ProRoot MTA: a clinical trial. 42 Jun SK, Yoon JY, Mahapatra C, et al. Ceria-incorporated MTA for
J Endod 2017;43(11):1786–1791 accelerating odontoblastic differentiation via ROS downregu-
25 Asl Aminabadi N, Satrab S, Najafpour E, Samiei M, Jamali Z, lation. Dent Mater 2019;35(9):1291–1299
Shirazi S. A randomized trial of direct pulp capping in primary 43 Opačić-Galić V, Petrović V, Jokanović V, Živković S. Histological
molars using MTA compared to 3Mixtatin: a novel pulp cap- evaluation of tissue reactions to newly synthetized calcium
ping biomaterial. Int J Paediatr Dent 2016;26(4):281–290 silicate-and hydroxyapatite-based bioactive materials - in vivo
26 Aminabadi NA, Huang B, Samiei M, Agheli S, Jamali Z, Shirazi study. Srp Arh Celok Lek 2017;145(0):63–63
S. A randomized trial using 3Mixtatin compared to MTA in pri- 44 Huq NL, Myroforidis H, Cross KJ, et al. The interactions of CPP-
mary molars with inflammatory root resorption: a novel end- ACP with saliva. Int J Mol Sci 2016;17(6):E915
odontic biomaterial. J Clin Pediatr Dent 2016;40(2):95–102 45 Heller D, Helmerhorst EJ, Oppenheim FG. Saliva and serum
27 Nowicka A, Wilk G, Lipski M, Kołecki J, Buczkowska-Radlińska protein exchange at the tooth enamel surface. J Dent Res
J. Tomographic evaluation of reparative dentin formation 2017;96(4):437–443
after direct pulp capping with Ca(OH)2, MTA, Biodentine, 46 Gibbins HL, Yakubov GE, Proctor GB, Wilson S, Carpenter GH.
and dentin bonding system in human teeth. J Endod What interactions drive the salivary mucosal pellicle forma-
2015;41(8):1234–1240 tion? Colloids Surf B Biointerfaces 2014;120:184–192
28 Kang CM, Kim SH, Shin Y, et al. A randomized controlled trial 47 Culp DJ, Robinson B, Parkkila S, et al. Oral colonization by
of ProRoot MTA, Ortho MTA and RetroMTA for pulpotomy in Streptococcus mutans and caries development is reduced
primary molars. Oral Dis 2015;21(6):785–791 upon deletion of carbonic anhydrase VI expression in saliva.
29 Bonte E, Beslot A, Boukpessi T, Lasfargues JJ. MTA versus Biochim Biophys Acta 2011;1812(12):1567–1576
Ca(OH)2 in apexification of non-vital immature perma- 48 Hannig M, Hannig C. Nanomaterials in preventive dentistry.
nent teeth: a randomized clinical trial comparison. Clin Oral Nat Nanotechnol 2010;5(8):565–569
Investig 2015;19(6):1381–1388 49 Khurshid Z, Zafar M, Qasim S, Shahab S, Naseem M, AbuReqaiba
30 Petrou MA, Alhamoui FA, Welk A. Altarabulsi MB, Alkilzy M, A. Advances in nanotechnology for restorative dentistry.
H Splieth C. A randomized clinical trial on the use of medical Materials (Basel) 2015;8(2):717–731
Portland cement, MTA and calcium hydroxide in indirect pulp 50 Kanaparthy R, Kanaparthy A. The changing face of dentistry:
treatment. Clin Oral Investig 2014;18(5):1383–1389 nanotechnology. Int J Nanomedicine 2011;6:2799–2804
31 Hilton TJ, Ferracane JL, Mancl L; Northwest Practice-based 51 Subramani K, Ahmed W, Hartsfield JK, Nanobiomaterials in
Research Collaborative in Evidence-based Dentistry (NWP). Clinical Dentistry; 2012
Comparison of CaOH with MTA for direct pulp capping: a PBRN 52 Cicciù M, Cervino G, Terranova A, et al. Prosthetic and mechan-
randomized clinical trial. J Dent Res 2013;92(7(Suppl):16S–22S ical parameters of the facial bone under the load of differ-
32 Gandolfi MG, Parrilli AP, Fini M, Prati C, Dummer PM. 3D ent dental implant shapes: a parametric study. Prosthesis
micro-CT analysis of the interface voids associated with 2020;1:41–53
Thermafil root fillings used with AH Plus or a flowable MTA 53 Cicciù M. Prosthesis: new technological opportunities and
sealer. Int Endod J 2013;46(3):253–263 innovative biomedical devices. Prosthesis 2020;1:1–2
33 Bernabé PF, Gomes-Filho JE, Bernabé DG, et al. Sealing ability 54 Crimi S, Fiorillo L, Bianchi A, et al. Herpes virus, oral clini-
of MTA used as a root end filling material: effect of the sonic cal signs and QoL: systematic review of recent data. Viruses
and ultrasonic condensation. Braz Dent J 2013;24(2):107–110 2019;11(5):463
34 Sönmez IS, Oba AA, Sönmez D, Almaz ME. In vitro evaluation 55 Zhang N, Zhang K, Xie X, et al. Nanostructured polymeric
of apical microleakage of a new MTA-based sealer. Eur Arch materials with protein-repellent and anti-caries properties for
Paediatr Dent 2012;13(5):252–255 dental applications. Nanomaterials (Basel) 2018;8(6):393
35 Leye Benoist F, Gaye Ndiaye F, Kane AW, Benoist HM, Farge 56 Guazzo R, Gardin C, Bellin G, et al. Graphene-based nanomate-
P. Evaluation of mineral trioxide aggregate (MTA) versus rials for tissue engineering in the dental field. Nanomaterials
calcium hydroxide cement (Dycal(®) ) in the formation of (Basel) 2018;8(5):349
a dentine bridge: a randomised controlled trial. Int Dent 57 Troiano G, Laino L, Cicciù M, et al. Comparison of two routes of
J 2012;62(1):33–39 administration of dexamethasone to reduce the postoperative
36 Ghoddusi J, Shahrami F, Alizadeh M, Kianoush K, Forghani sequelae after third molar surgery: a systematic review and
M. Clinical and radiographic evaluation of vital pulp ther- meta-analysis. Open Dent J 2018;12:181–188
apy in open apex teeth with MTA and ZOE. N Y State Dent J 58 Laino L, Cicciù M, Fiorillo L, et al. Surgical risk on patients
2012;78(3):34–38 with coagulopathies: guidelines on hemophiliac patients
37 Hansen SW, Marshall JG, Sedgley CM. Comparison of intracanal for oro-maxillofacial surgery. Int J Environ Res Public Health
EndoSequence root repair material and ProRoot MTA to induce 2019;16(8):1386
pH changes in simulated root resorption defects over 4 weeks 59 Fiorillo L, De Stefano R, Cervino G, et al. Oral and psycho-
in matched pairs of human teeth. J Endod 2011;37(4):502–506 logical alterations in haemophiliac patients. Biomedicines
38 Yildirim T, Taşdemir T, Orucoglu H. The evaluation of the influ- 2019;7(2):33
ence of using MTA in teeth with post indication on the api- 60 Cervino G, Fiorillo L, Monte IP, et al. Advances in antiplatelet
cal sealing ability. Oral Surg Oral Med Oral Pathol Oral Radiol therapy for dentofacial surgery patients: focus on past and
Endod 2009;108(3):471–474 present strategies. Materials (Basel) 2019;12(9):1524
39 Jinga SI, Voicu G, Stoica-Guzun A. Stroescu M, Grumezescu 61 Herford AS, Lu M, Akin L, Cicciù M. Evaluation of a porcine
AM, Bleotu C. Biocellulose nanowhiskers cement compos- matrix with and without platelet-derived growth factor for
ites for endodontic use. Dig J Nanomater Biostructures bone graft coverage in pigs. Int J Oral Maxillofac Implants
2014;9(2):543–550 2012;27(6):1351–1358
40 Voicu G, Bǎdǎnoiu AI, Ghiţulicǎ CD, Andronescu E. Sol- 62 Sambataro S, Cervino G, Bocchieri S, La Bruna R, Cicciù M. TMJ
gel synthesis of white mineral trioxide aggregate with dysfunctions systemic implications and postural assessments:

European Journal of Dentistry

 A Review on Clinical Applications of MTA  Cervino et al. 9

a review of recent literature. J Funct Morphol Kinesiol 71 de Oliveira NG, de Souza Araújo PR, da Silveira MT, Sobral APV,
2019;4:58 Carvalho MV. Comparison of the biocompatibility of calcium
63 Sambataro S, Bocchieri S, Cervino G, et al. Correlations between silicate-based materials to mineral trioxide aggregate: system-
malocclusion and postural anomalies in children with mixed atic review. Eur J Dent 2018;12(2):317–326
dentition. J Funct Morphol Kinesiol 2019;4:45 72 Ferreira MM, Botelho MF, Abrantes M, Carvalho L, Carrilho E.
64 Cicciù M, Risitano G, Lo Giudice G, Bramanti E. Periodontal Histologic evaluation of the effect of mineral trioxide aggre-
health and caries prevalence evaluation in patients affected by gate-Fillapex as a root canal sealer in rat teeth submitted to
Parkinson’s disease. Parkinsons Dis 2012;2012:541908 late replantation. Eur J Dent 2017;11(1):89–93
65 Cicciù M, Bramanti E, Cecchetti F, Scappaticci L, Guglielmino 73 Scrascia R, Fiorillo L, Gaita V, Secondo L, Nicita F, Cervino G.
E, Risitano G. FEM and Von Mises analyses of different den- Implant-supported prosthesis for edentulous patient rehabil-
tal implant shapes for masticatory loading distribution. Oral itation. From temporary prosthesis to definitive with a new
Implantol (Rome) 2014;7(1):1–10 protocol: a single case report. Prosthesis 2020;2(1):10–24
66 Cicciù M, Beretta M, Risitano G, Maiorana C. Cemented-retained 74 Ortensi L, Vitali T, Bonfiglioli R, Grande F. New tricks in the
vs screw-retained implant restorations: an investigation on preparation design for prosthetic ceramic laminate veeners.
1939 dental implants. Minerva Stomatol 2008;57(4):167–179 Prosthesis 2019;1(1):29–40
67 Algarni AA, Mussi MC, Moffa EB, et al. The impact of stannous, 75 Lee DS, Lim MJ, Choi Y, Rosa V, Hong CU, Min KS. Tooth discol-
fluoride ions and its combination on enamel pellicle proteome oration induced by a novel mineral trioxide aggregate-based
and dental erosion prevention. PLoS One 2015;10(6):e0128196 root canal sealer. Eur J Dent 2016;10(3):403–407
68 Rodríguez-Lozano FJ, López-García S, García-Bernal D, et al. In 76 Bayram E, Bayram HM. Fracture resistance of immature teeth
vitro effect of putty calcium silicate materials on human peri- filled with mineral trioxide aggregate, bioaggregate, and
odontal ligament stem cells. Appl Sci 2020;10(1):325 Biodentine. Eur J Dent 2016;10(2):220–224
69 Tatullo M, Spagnuolo G, Codispoti B, et al. PLA-based miner- 77 Akcay H, Arslan H, Akcay M, Mese M, Sahin NN. Evaluation of
al-doped scaffolds seeded with human periapical cyst-derived the bond strength of root-end placed mineral trioxide aggre-
MSCs: a promising tool for regenerative healing in dentistry. gate and Biodentine in the absence/presence of blood contam-
Materials (Basel) 2019;12(4):E597 ination. Eur J Dent 2016;10(3):370–375
70 Spagnuolo G, Codispoti B, Marrelli M, Rengo C, Rengo S, Tatullo
M. Commitment of oral-derived stem cells in dental and max-
illofacial applications. Dent J (Basel) 2018;6(4):E72

European Journal of Dentistry