materials

Review
Calcium Silicate-Based Root Canal Sealers: A Narrative Review
and Clinical Perspectives
Germain Sfeir 1 , Carla Zogheib 1 , Shanon Patel 2 , Thomas Giraud 3 , Venkateshbabu Nagendrababu 4
and Frédéric Bukiet 3, *

1 Department of Endodontics, Faculty of Dental Medicine, Saint Joseph University of Beirut,

Beirut 17-5208, Lebanon; germain.sfeir@usj.edu.lb (G.S.); carla.zogheibmoubarak@usj.edu.lb (C.Z.)
2 King’s College London Dental Institute, Guy’s Tower, Guy’s Hospital, St. Thomas’ Street,
London SE1 9RT, UK; shanonpatel@gmail.com
3 Assistance Publique des Hôpitaux de Marseille, 13005 France; Aix Marseille Univ, CNRS, ISM,
Inst Movement Sci, 13288 Marseille, France; thomas.giraud@univ-amu.fr
4 Department of Preventive and Restorative Dentistry, College of Dental Medicine, University of Sharjah,
Sharjah 27272, United Arab Emirates; hivenkateshbabu@yahoo.com
* Correspondence: frederic.bukiet@univ-amu.fr; Tel.: +33-(0)6-4395-2183

Abstract: Over the last two decades, calcium silicate-based materials have grown in popularity.
As root canal sealers, these formulations have been extensively investigated and compared with
conventional sealers, such as zinc oxide–eugenol and epoxy resin-based sealers, in in vitro studies
that showed their promising properties, especially their biocompatibility, antimicrobial properties,
and certain bioactivity. However, the consequence of their higher solubility is a matter of debate and





 still needs to be clarified, because it may affect their long-term sealing ability. Unlike conventional
Citation: Sfeir, G.; Zogheib, C.; Patel,
sealers, those sealers are hydraulic, and their setting is conditioned by the presence of humidity.
S.; Giraud, T.; Nagendrababu, V.; Current evidence reveals that the properties of calcium silicate-based sealers vary depending on their
Bukiet, F. Calcium Silicate-Based Root formulation. To date, only a few short-term investigations addressed the clinical outcome of calcium
Canal Sealers: A Narrative Review silicate-based root canal sealers. Their use has been showed to be mainly based on practitioners’
and Clinical Perspectives. Materials clinical habits rather than manufacturers’ recommendations or available evidence. However, their
2021, 14, 3965. https://doi.org/ particular behavior implies modifications of the clinical protocol used for conventional sealers. This
10.3390/ma14143965 narrative review aimed to discuss the properties of calcium silicate-based sealers and their clinical
implications, and to propose rational indications for these sealers based on the current knowledge.
Academic Editors:
Laura-Cristina Rusu and
Keywords: calcium silicate-based root canal sealer; hydraulic root canal sealer; root canal obturation;
Lavinia Cosmina Ardelean
root canal treatment

Received: 12 June 2021

Accepted: 8 July 2021
Published: 15 July 2021
1. Introduction
Publisher’s Note: MDPI stays neutral
Despite numerous technological leaps, the purpose of root canal treatment is still
with regard to jurisdictional claims in
prevention and healing of apical periodontitis by achieving proper disinfection and three-
published maps and institutional affil- dimensional filling of the root canal space [1]. Root canal filling prevents diffusion of
iations. microorganisms and their byproducts and has been subject to various modifications from
the use of solid material to gutta-percha cones in association with root canal sealers [2].
Various types of root canal sealers have been developed, such as zinc oxide–eugenol,
epoxy resin, glass ionomer, and silicone-based sealers [3]. In the last decade, calcium
Copyright: © 2021 by the authors.
silicate-based sealers (CSBS), often called “bioceramic” sealers, have been released and ex-
Licensee MDPI, Basel, Switzerland.
tensively investigated by comparing their properties to those of zinc oxide–eugenol-based
This article is an open access article
and epoxy resin-based sealers [4,5]. Many formulations are available on the market. Unlike
distributed under the terms and conventional root canal sealers, CSBS are hydraulic and hygroscopic with a particular
conditions of the Creative Commons setting process [6]. CSBS exhibit several interesting properties, especially biocompatibility,
Attribution (CC BY) license (https:// antimicrobial properties, and bioactivity [7–12]. Nevertheless, the dimensional stability of
creativecommons.org/licenses/by/ CSBS showed contradicting results among studies; while some studies showed no shrink-
4.0/). age upon setting, other demonstrated a slight expansion [3,4]. Mineral layer formation

Materials 2021, 14, 3965. https://doi.org/10.3390/ma14143965 https://www.mdpi.com/journal/materials

Materials 2021, 14, 3965 2 of 21

during setting induces a chemical bond with dentin walls in biological environment, which
contributes to their sealing ability [4–6].
To date, if laboratory studies showed favorable results regarding CSBS’ physico-
chemical and biological properties [13–18], only a few short-term investigations addressing
the clinical outcome of CSBS have been published [19–21]. Moreover, a recent survey
demonstrated that the methods of using CSBS in clinical practice were variable and based
on practitioners’ habits rather than manufacturers’ recommendations or available evidence
on these sealers [22]. This highlights the possible inappropriate use of CSBS, which
may negatively impact the obturation, and thus the outcome of the root canal treatment.
Moreover, this exposes a knowledge gap between the fundamental research on CSBS
and their clinical application, justifying the need to better connect these two aspects. The
number of CSBS formulations is strongly increasing over time, so it is of prime importance
to better understand their specificities and their clinical perspectives.
Hence, the current review aimed to discuss the properties of CSBS and their clinical
implications, and to propose rational indications based on the current knowledge and
CSBS specificities.

1.1. Literature Search Methodology

Two independent reviewers (G.S., C.Z.) performed a comprehensive literature search
to identify related studies in PubMed, Scopus, Web of Science, and Cochrane Library
databases, between 1 January 2010 and 15 May 2021. The following search strategy
was used to find relevant studies: (bioceramic sealer OR bioceramic root canal sealer)
OR (hydraulic sealer OR hydraulic root canal sealer) OR (calcium silicate-based sealer
OR calcium silicate-based root canal sealer) AND (root canal OR endodontics OR root
canal treatment) OR (root canal filling OR root canal obturation). The references list of
the included studies and previously published reviews were searched. Laboratory and
clinical studies investigating at least one of the CSBS’ properties/outcome were included
in the review. The studies performed in training simulated resin teeth or animal teeth
were excluded.

1.2. Terminology
Rheological properties of calcium silicate-based materials such as ProRoot® Min-
eral trioxide aggregate (MTA) (Denstply Sirona, Ballaigues, Switzerland) or Biodentine
(Septodont, Saint-Maur-des-Fossés, France) were not appropriate to be used as a root canal
sealer in association with gutta-percha for obturation. Therefore, in the past 10 years,
specific root canal sealer formulations intended for this purpose were developed. These
sealers are usually called “bioceramics” by most manufacturers for marketing purpose.
This term is not accurate enough [6]. Indeed, chemically, bioceramics represent a large
family of biomaterials in terms of composition, and further involve a sintering step in their
implementation [23]. Therefore, this new family of root canal sealers should rather be
identified as “calcium silicate-based sealers” (CSBS) or “hydraulic calcium silicate-based
sealers”, due to their hydrophilic nature, chemical composition, and setting reaction [24].
CSBS are usually formulated from synthetic calcium silicate or from Portland/MTA. It is of
prime importance to highlight that CSBS’ properties can strongly vary depending on the
additives included in each formulation [25], and potentially influence their indications and
clinical application.

2. Review
2.1. Physico-Chemical Properties
2.1.1. Setting Reaction and Setting Time
Unlike conventional sealers, CSBS are hydraulic and need water to trigger the setting
process (Figure 1). In the presence of water, calcium silicates form a calcium silicate hydrate
gel (CSH, CaO·SiO·H2 O), which leads to calcium hydroxide (CaOH2 ) formation [26], as
shown in Figure 1. Ion exchanges, predominantly silicon (Si4+ ) from CSH, and calcium
 2. Review
2.1. Physico-Chemical Properties
2.1.1. Setting Reaction and Setting Time
Unlike conventional sealers, CSBS are hydraulic and need water to trigger the setting
Materials 2021, 14, 3965 3 of 21
process (Figure 1). In the presence of water, calcium silicates form a calcium silicate hy-
drate gel (CSH, CaO·SiO·H2O), which leads to calcium hydroxide (CaOH2) formation [26],
as shown in Figure 1. Ion exchanges, predominantly silicon (Si4+) from CSH, and calcium
2+) and hydroxyl (OH-−
(Ca2+ ) )ions
(Ca ) and hydroxyl ionsfrom
fromcalcium
calciumhydroxide
hydroxidedissociation,
dissociation, contribute
contribute to CSBS’
biological properties
biological properties[7,8,10,12].
[7,8,10,12].These
Theseions
ionsprovide
providedifferent
differenteffects; 4+4+and
effects;SiSi Ca2+2+ promote
andCa promote
biomineralization, while OH −
OH ions
- ionsincrease
increase pHpH environment provide antimicrobial
environment and provide antimicrobial
properties. Finally,
properties. Finally, in
in the
the presence
presence of of phosphate,
phosphate, microscopic
microscopic investigations
investigations showed
showed thatthat
CSBS formed an interfacial layer at the dentin wall known as the “mineral infiltration
the dentin wall known as the “mineral infiltration
zone”
zone” duedueto
tocalcium
calciumphosphate
phosphateformation
formation inducing apatite
inducing precursors
apatite precursorsandandhydroxyapatite
hydroxyap-
precipitation on theonsurface
atite precipitation of theofmaterial
the surface [24,27,28].
the material [24,27,28].

Figure 1.
Figure 1. Setting reaction
reaction of
of CSBS
CSBS consisting
consisting of
of two
two hydration
hydration reactions.
reactions.

Setting time is evaluated

evaluated by by analyzing
analyzing created
created indentations
indentations on on aa material
material sample’s
sample’s
surface; when indentations cease to be visible, visible, setting
setting time
time can
can bebe recorded
recorded [29,30].
[29,30]. CSBS
CSBS
overall
overall reported
reported aa shorter
shorter setting
setting time
time compared
compared to to conventional
conventional formulations
formulations such such asas AH
AH
Plus ®
Plus® (Dentsply
(Dentsply Sirona,
Sirona,York,
York,PA,PA,USA)
USA) [3,31]. However,
[3,31]. However, prolonged
prolonged setting timestimes
setting werewere
also
highlighted [32], [32],
also highlighted depending
dependingnot only on formulation,
not only on formulation, but but
alsoalso
on root canal
on root moisture,
canal moisture,as
it has been noted that when the root canal is dry, setting time tends to
as it has been noted that when the root canal is dry, setting time tends to increase [18]. increase [18]. This
explains why setting
This explains timestimes
why setting vary between clinical
vary between trials and
clinical trialslaboratory studies,
and laboratory and small
studies, and
amounts of fluids in contact with sealers may affect the latter [33]. For
small amounts of fluids in contact with sealers may affect the latter [33]. For instance, instance, it has beenit
demonstrated in vitro that
has been demonstrated inBioRoot™
vitro that RCS (Septodont,
BioRoot™ Saint-Maur-des-Fossés,
RCS (Septodont, France) had
Saint-Maur-des-Fossés,
aFrance)
settinghad
time inferiortime
to 6inferior
h, while ®
a setting to MTA Fillapex
6 h, while (Angelus,
MTA Fillapex Londrina,Londrina,
® (Angelus, Brazil) did not
Brazil)
completely set within one week [34]. This lack of setting was also
did not completely set within one week [34]. This lack of setting was also reported by reported by another
study
another[35] also[35]
study investigating BioRoot™
also investigating RCS thatRCS
BioRoot™ indicated an influence
that indicated of contact
an influence media
of contact
(culture media) on the observed setting times. By contrast, when
media (culture media) on the observed setting times. By contrast, when simulating differ-simulating different
conditions (with an anincreased fluid intake), thethesetting ®
ent conditions (with increased fluid intake), settingtime
timefor forboth
both ®
EndoSequence
EndoSequence®
BC Sealer™ (Brasseler
BC Sealer™ (BrasselerUSA,USA,Savannah,
Savannah,GA, GA,USA) USA) andandMTAMTA Fillapex
Fillapex ® was was inferior
inferior to 3 to
h,
3which
h, which is much shorter than epoxy or zinc oxide–eugenol-based
is much shorter than epoxy® or zinc oxide–eugenol-based sealers sealers [3]. Another
[3]. Another study
study comparing EndoSequence BC Sealer™ and EndoSequence® BC Sealer™ HiFlow
comparing EndoSequence® BC Sealer™ and EndoSequence® BC Sealer™ HiFlow (Bras-
(Brasseler USA, Savannah, GA), reported comparable initial setting times of 4 h for both
seler USA, Savannah, GA), reported comparable initial setting times of 4 h for both for-
formulations [36]. Although variable, these values remain generally lower than those
mulations [36]. Although variable, these values remain generally lower than those of con-
of conventional sealers (zinc oxide–eugenol and resin-based). Finally, it was shown that
ventional sealers (zinc oxide–eugenol and resin-based). Finally, it was shown that apply-
applying heat during root canal filling resulted in an extended setting time for premixed
ing heat during root canal ® and filling resulted in® an extended setting time for premixed CSBS
CSBS such as HiFlow Endosequence BC Sealer™, while the setting process was
such as HiFlow® and Endosequence® BC Sealer™, while the setting process was faster for
faster for BioRoot™ RCS, highlighting again the influence of the formulation on sealer
BioRoot™ RCS, highlighting again the influence of the formulation on sealer properties
properties [37].
[37].
2.1.2. Flowability
Unlike the first calcium silicate-based materials, with inappropriate flowability/
consistency for root canal filling [38], CSBS flowability should allow good sealer dis-
tribution into the ramifications/irregularities of the root canal space. The flow values
are studied by placing a sample of mixed material between two glass plates with the
application of a mass on top. At the end of the assay, the sample diameter is determined
and used to assess the material flow capacity and must be superior or at least 17 mm [29,30]
Materials 2021, 14, 3965 4 of 21

(ANSI/ADA, 2000; ISO 6876, 2012). Among available studies, it has been demonstrated
that MTA Fillapex® , EndoSequence® BC Sealer™, and Endoseal MTA® (Maruchi, Wonju,
Korea) [3,27,35,39,40] met the minimum expected values, and the highest values for MTA
Fillapex® were generally reported. However, while BioRoot™ RCS was characterized by
results slightly below the minimum standard (16 mm) [13], it was also characterized as
meeting the standard requirements with values above 21 mm [35], but decreasing with
heat application [41]. HiFlow® formulation exhibited the highest flow as compared to
EndoSequence® BC Sealer™, although it decreased with heat application [36]. Overall,
based on the available literature, CSBS flowability should be considered as overall compa-
rable to the conventional sealers, especially epoxy resin-based sealers such as AH Plus® .

2.1.3. Wettability
Root canal sealers should have a good wetting ability and adhesion to dentinal
walls [42]. Wettability reflects the spreading ability and the capability of sealers to penetrate
into both the main and lateral canals, as well as into the dentinal tubules [43]. Since CSBS
are hydrophilic, this might induce a good spreading ability on wet root canal walls [4].
This was confirmed by a recent study showed the best wetting ability and adhesion for
EndoSequence® BC Sealer™ and EndoSeal MTA® compared to AH Plus® [42].

2.1.4. Film Thickness

Film thickness of tested material is determined under stress by placing the sample of
the sealer between two glass slides and a load application. According to ISO6876/2012
and ANSI/ADA no 57, film thickness must not exceed 50 µm for sealers, as an end result
of the test conditions [29,30]. This property is respected by various formulations such
as EndoSequence® BC Sealer™ HiFlow® , Endoseal MTA® , and MTA Fillapex® [3,35,36],
presenting overall higher values compared to AH Plus® . Moreover, BioRoot™ RCS ex-
hibited the highest values of film thickness [35], and other studies described this property
as slightly above the standard values [13,41]. Here too, film thickness values were re-
ported to be increased by heat application for BioRoot™ RCS, EndoSequence® BC Sealer™,
and EndoSequence® BC Sealer™ HiFlow® [36,41]. Moreover, it can be considered that
this characteristic for CSBS should be put in perspective with their better dimensional
stability and their use with sealer-based obturation techniques such as cold hydraulic
condensation (CHC).

2.1.5. Dimensional Stability

CSBS dimensional stability is overall better than the one of conventional sealers,
especially zinc oxide–eugenol-based sealers, which tend to shrink upon setting, especially
if sealer film thickness increases [44–46]. It should be mentioned that this parameter is
no longer present in the latest ISO standard. As initially demonstrated for MTA-based
formulations, CSBS may present a slight hygroscopic expansion up to 0.2%, but this was
not highlighted for all formulations [44].
Lee et al. (2017) compared dimensional stability between AH Plus® , AD Seal® (Meta
Biomed, Cheongju, Korea), and Radic-Sealer ® (Seoul, Korea) and the CSBS formulation
Endoseal MTA® . It was shown that AH Plus® and Endoseal MTA® revealed the least
dimensional changes, especially for Endoseal MTA® , which remained lower than AH
Plus® 30 days later. The other two resin-based formulations had higher values than recom-
mended [39]. In another study, no significant difference in volumetric change between AH
Plus® and TotalFill BC sealer was reported [27]. On the other hand, MTA Fillapex® showed
a slight shrinkage upon setting (which might have been due to the presence of resin in
this formulation), while EndoSequence® BC Sealer™ demonstrated an expansion, but
inferior to 0.1% [3]. The expansion of EndoSequence® BC Sealer™ might be influenced by
direct contact of CSBS with enzymes [47]. By contrast, using micro-CT, a higher volumetric
loss also was reported [32], but to a lesser extent with the use of PBS [26]. The better
dimensional stability of CSBS is often highlighted as the main reason for allowing their
 AH Plus® and TotalFill BC sealer was reported [27]. On the other hand, MTA Fillapex®
showed a slight shrinkage upon setting (which might have been due to the presence of
resin in this formulation), while EndoSequence® BC Sealer™ demonstrated an expansion,
but inferior to 0.1% [3]. The expansion of EndoSequence® BC Sealer™ might be influenced
Materials 2021, 14, 3965 by direct contact of CSBS with enzymes [47]. By contrast, using micro-CT, a higher volu- 5 of 21
metric loss also was reported [32], but to a lesser extent with the use of PBS [26]. The better
dimensional stability of CSBS is often highlighted as the main reason for allowing their
use with cold hydraulic condensation, especially the single-cone (SC) technique (Figure
use with cold hydraulic condensation, especially the single-cone (SC) technique (Figure 2).
2). This aspect must also take into account the solubility of CSBS.
This aspect must also take into account the solubility of CSBS.

Figure 2. Updated single-cone technique with CSBS (sealer-based obturation) considering their enhanced dimensional
Figure 2. Updated single-cone technique with CSBS (sealer-based obturation) considering their enhanced dimensional
stability.
stability.
2.1.6. Solubility of CSBS
2.1.6. Solubility of CSBS
Overall, CSBS solubility indicated higher values than those of conventional sealers
Overall,
without CSBS solubility
necessarily respecting indicated higher values
the specifications of the than those of(less
standards conventional
than 3%) sealers
[29,30].
without necessarily respecting the specifications of the
Systematically, studies reported that CSBS present higher solubility compared standards (less than 3%)to[29,30].
epoxy
Systematically,
resin-based sealersstudies reported that CSBS However,
[3,26,27,32,34–36,47,48]. present higher whilesolubility
some studies comparedreportedto values
epoxy
resin-based
of solubilitysealers [3,26,27,32,34–36,47,48].
with respect to ISO 6876/2012 However,
and ANSI/ADAwhile some studies reported values
recommendations, others
of solubility with respect to ISO 6876/2012 and ANSI/ADA
did not. Indeed, although the standard recommends using water, solubility values mayrecommendations, others did
not. Indeed, although the standard recommends using water,
strongly differ depending on experimental conditions such as setting conditions and con- solubility values may
strongly
tact liquiddiffer depending
(water, on experimental
PBS, culture conditions
media); for example, such as reported
solubility setting conditions
for BioRoot™and con-
RCS
tact
andliquid
MTA (water, ®
FillapexPBS, culturethe
fulfilled media);
standard for example, solubility (inferior
recommendations reportedto for3%),
BioRoot™
and theRCS use
and MTA
of PBS Fillapex
lowered RCS solubility [34]. This was also the case for MTA Fillapex®
® fulfilled the standard recommendations (inferior to 3%), and the use
BioRoot™
of
andPBS lowered BioRoot™
EndoSequence ® BC Sealer™
RCS solubility
in the study[34].ofThis
Zhou was also
et al. the case
(2013), which forused
MTAa Fillapex
modified ®

and EndoSequence
sample setting method ® BCand Sealer™ in the
fulfilled thestudy of Zhou
weight-loss et al. (2013), [3].
requirements which used astudy
Another modified
indi-
sample
cated lowsetting method
solubility ratesand
forfulfilled
EndoSequence ® BC Sealer™
the weight-loss requirements [3]. Another
and EndoSequence ® BC study
Sealer™ in-
dicated low solubility
HiFlow formulations rates
[36]. for EndoSequence
Moreover, ® BC Sealer™ and
solubility of EndoSequence ® BC EndoSequence
Sealer™ was higher ® BC
Sealer™
when in HiFlow formulations
contact with biological [36]. Moreover,
fluids such as solubility
the Esterase of enzyme
EndoSequence ® BC Sealer™
as compared to PBS
was higher when
but remained in contact with
in compliance withbiological fluids such
the ISO standard as the Esterase
requirement in bothenzymeconditionsas com-
[47].
On thetoother
pared hand,
PBS but other studies
remained have reported
in compliance with thevalues much higher
ISO standard requirement than the standard
in both con-
requirements
ditions [47]. On (frequently
the other above 10%), studies
hand, other also usinghaveclassical
reported or various
values muchassay higher
conditions,
than andthe
concerned the previously mentioned CSBS formulations [26,27,32,35,48].
standard requirements (frequently above 10%), also using classical or various assay con-
Investigation
ditions, and concerned of CSBS’ solubility ismentioned
the previously a major matterCSBSofformulations
debate. Indeed, higher solubility
[26,27,32,35,48].
of CSBS might leadoftoCSBS’
Investigation jeopardize
solubilitytheirislong-term sealing
a major matter of ability
debate.[5]. However,
Indeed, microscopic
higher solubility
analysis
of has demonstrated
CSBS might lead to jeopardizemineral deposition
their long-term and an infiltration
sealing ability [5].zone into themicroscopic
However, dentin [26],
which might
analysis call into question
has demonstrated mineral thedeposition
above concern.and an Indeed, it must
infiltration zone be into pointed out [26],
the dentin that
CSBS’ biological properties can be explained by their solubility
which might call into question the above concern. Indeed, it must be pointed out that and related release of
ions [49], which leads to specific interaction between CSBS and the
CSBS’ biological properties can be explained by their solubility and related release of ions dentin walls (mineral
infiltration zone). Furthermore, solubility may be overestimated due to the chemical
class of CSBS, which could explain the discrepancies sometimes found between the high
solubility values and the relatively lower ones concerning dimensional variations [27,32].
These contradictory results might be explained by the bias in the solubility of CSBS due to
their hydrophilic nature. Moreover, since fluid environments (use of culture media) might
strongly influence solubility results [35], it can be hypothesized that in vivo application of
endodontic sealer should be relatively different with notably limited contact with aqueous
fluids compared to in vitro test conditions.
Materials 2021, 14, 3965 6 of 21

2.1.7. Adhesion–Interaction with Dentin Walls

CSBS adhesion and interaction with dentin walls were investigated by push-out
test, filtration assays, or microscopy analysis. As mentioned previously, CSBS form a
specific interfacial layer at the dentin walls known as the mineral infiltration zone [49]. The
sealer’s hydration products alter the collagen of the interfacial dentin due to their alkaline
effects [50]. This alteration leads to the formation of a porous structure promoting the
diffusion of high concentrations of Ca2+ , OH− , and CO3 2− ions, favoring mineralization
in this area [18]. This chemical and micromechanical interaction (tag-like structures)
represents the main reason for assessment of the adhesion between CSBS and dentin [49,51].
Laboratory studies found higher push-out bond strength (POBS) values for AH Plus®
when compared to MTA Fillapex® , TotalFill® BC Sealer™, and BioRootTM RCS [52,53]. On
the other hand, Tuncel et al. (2015) compared the POBS of AH Plus® to iRoot SP® (IBC,
Burnaby, BC, Canada), and found that iRoot SP® had significantly better results [54]. CSBS
and conventional sealers showed variable results regarding bond strength and adhesion
to the dentin walls; however, only one study showed no difference between CSBS and
resin-based sealers [55]. Some variations have also been demonstrated between different
CSBS formulations and depending on the root canal filling technique used; Delong et al.
(2015) demonstrated that the lowest adhesion was found with MTA Plus® (Prevest, Jammu,
India) when warm obturation techniques were used. However, BC Sealer® had higher
bond-strength values than MTA Plus® when both were used with the SC technique [56].

2.1.8. Adhesion between the Gutta-Percha and the Sealer

CSBS are hydrophilic materials and the surface of gutta-percha cones is hydrophobic,
which is why this interface remains questionable regarding potential micro-organism leak-
age [22]. Some manufacturers have proposed different strategies to enhance the adhesion
between CSBS and gutta-percha. The use of specific pre-impregnated gutta-percha cones
with “bioceramic” nanoparticles has been suggested with premixed formulations, while
Septodont claimed the inclusion of an organic polymer (povidone) in their BioRoot™ RCS
formulation. The only available study showed that the interface between these specific
gutta-percha cones and the corresponding CSBS was not satisfactory [57]. Moreover, the
contact between gutta-percha and sodium hypochlorite for disinfection before any obtu-
ration technique has been shown to degrade the gutta-percha cones [58]. This led us to
wonder if specific coated gutta-percha cones may lose the claimed benefit when immersed
in sodium hypochlorite. To our knowledge, there is no available scientific evidence sup-
porting the use of specific pre-impregnated gutta-percha cones. Likewise, the effect of the
povidone included in BioRoot™ RCS has not been investigated yet.

2.1.9. Microhardness
Microhardness reflects the resistance of materials to deformation under a specific
load. This property is not a part of the ISO/ADA requirements, and so it has been rarely
investigated. Microhardness can be used as an indirect measurement of material setting [59].
The Vickers hardness test is used to assess the microhardness of sealers. Microhardness
may impact CSBS removal when a non-surgical retreatment is indicated [22,59].

2.1.10. Radiopacity
The ISO 6876 standard establishes 3 mm of aluminum (Al) as the minimum radiopacity
for 1 mm root canal sealer sample thickness, as is the case of ANSI/ADA specification
No. 57 [29,30]. Two main radio-opacifiers are generally included in CSBS formulations:
Portland/MTA based-formulations most often contain bismuth oxide [60,61], whereas
other CSBS generally include zirconium oxide in their formulations [38]. Overall, the
standard specifications are respected in all CSBS formulations [62]. Different formulations
of CSBS demonstrated higher radiopacity compared to the ISO standards. This was
demonstrated for BioRoot™ RCS [13], EndoSequence® BC Sealer™, EndosealMTA® , and
MTA Fillapex® [39]. TotalFill® BC Sealer HiFlow™ might exhibit an additional radiopacity
Materials 2021, 14, 3965 7 of 21

of 20% compared to standard TotalFill® BC Sealer™ according to the manufacturer’s

instructions (FKG Dentaire catalogue, La Chaux-De-Fonds, Switzerland).

2.2. Biological Properties

As previously presented, CSBS’ biological properties rely on a hydration reaction lead-
ing to CSH and calcium hydroxide formation. Indeed, hydration byproducts, OH− , Ca+2 ,
and Si+4 ions are involved in modulating environment alkalization and cell metabolism,
especially cell differentiation and tissue mineralization [63–65]. As a biomaterial, CSBS
formulations must notably be non-genotoxic and non-cytotoxic, while also exhibiting
antimicrobial properties and inducing appropriate host response in their specific use.
These capacities, which rely on biocompatibility, are, among others, framed and evaluated
through the ISO standard series 10993 [66]. Moreover, it is important to highlight that
these studied properties, mostly in vitro, vary according to the protocols used. Indeed,
biomaterial state (freshly mixed/set), type of contact (direct/extracts and associated dilu-
tions), and targeted organisms chosen (cell lines/primary cell culture, planktonic bacterial
strains/organized biofilms) will more or less accurately reflect the clinical use.

2.2.1. Genotoxicity and Cytotoxicity

Genotoxicity is assessed using various protocols to study DNA breaks or nucleus
division anomalies. In a study using a γ-H2AX foci assay, no difference in genotoxicity
was highlighted between unset formulations of CSBS (BioRoot™ RCS, iRoot SP® , MTA
Fillapex® ) in comparison to conventional sealers (epoxy- and methacrylate-based), except
a slight increase for iRoot SP® , while BioRoot™ RCS was revealed to be less genotoxic on
periodontal ligament (PDL) cells [67]. However, when compared to a zinc oxide–eugenol
formulation (Tubliseal), iRoot SP® and EndoSequence® BC Sealer ™ were shown to be the
least genotoxic using a comet assay (DNA breaks) on L929 murine fibroblasts [68]. Further-
more, when human gingival fibroblast cultures were submitted to unset EndoSequence®
BC Sealer™, it led to a reduced genotoxicity potential as compared to AH Plus using a
micronucleus assay [69]. Finally, set formulations of MTA Fillapex® and AH Plus® , al-
though depending on the concentration and the incubation time used, were shown to be
more genotoxic by micronucleus assay on V79 fibroblasts as compared to classical MTA
formulation [70].
In parallel, cytotoxicity was studied on PDL cells using unset biomaterial samples,
and demonstrated a reduced effect of BioRoot™ RCS, iRootSP® , and MTA Fillapex® as
compared to other resin-based sealers such as AH Plus® . However, MTA Fillapex® was
revealed to be three times more cytotoxic than BioRoot™ RCS [67]. In another study,
evaluating both freshly mixed and set sealer sample on human PDL cells, it was shown that
BioRoot RCS was the least cytotoxic in both set and freshly mixed conditions, even allowing
cell proliferation [71]. By contrast AH Plus® was revealed to be cytotoxic in a freshly mixed
condition, but not after setting, while MTA Fillapex and Pulp Canal Sealer (PCS) were
characterized as cytotoxic in both fresh and set states [71]. Close results were obtained
while comparing AH Plus MTA Fillapex® and EndoSequence® BC Sealer™ on gingival
fibroblasts, indicating higher cell viabilities for EndoSequence® BC Sealer™ in fresh/set
conditions [72]. Conversely, AH Plus® was more cytotoxic when freshly mixed, while
MTA Fillapex® was reported to be cytotoxic in both conditions [72]. Using set biomaterial
samples, it was demonstrated on L929 murine fibroblasts by MTT assay that the zinc
oxide–eugenol formulation was the more cytotoxic as compared to EndoSequence® BC
Sealer™ and iRoot SP® [68]. Using direct contact with set biomaterial on isolated PDL cells,
a much greater number of present cells for BioRoot™ RCS were demonstrated compared
to a zinc oxide–eugenol (PCS) [12]. This has also been demonstrated on cell proliferation
using sealer extracts, leading to a greater decrease with the use of PCS [12]. These results
were confirmed in another study that used sealer extract on human PDL fibroblasts, and
which demonstrated an increase of cell proliferation with the use of BioRoot™ RCS extracts
as compared to PCS [73]. Moreover, a much lower CSBS cytotoxicity was also highlighted
Materials 2021, 14, 3965 8 of 21

using an adenosine triphosphate luminescence assay on a murine osteoblast precursor

cell line [74]. Indeed, AH Plus® was revealed to be cytotoxic at concentrations a hundred
times lower than EndoSequence® BC Sealer™ and ProRoot ES (Dentsply Tulsa Dental
Specialties, Tulsa, OK, USA) [74]. Cytotoxicity was also investigated in human PDL stem
cells (PDLSCs) in two works by Collado-Gonzalez et al. that evaluated set biomaterial
sample effects and indicated an overall cytotoxicity of MTA Fillapex® , Endoseal MTA® ,
and AH Plus® , while BioRoot™ RCS was characterized as highly biocompatible [7,75].
Similar findings have been reported in human PDLSCs by Rodríguez-Lozano et al., who
concluded that TotalFill® BC Sealer™ induced a lower cytotoxicity as compared to MTA
Fillapex® and AH Plus® [76]. Finally, it was recently also demonstrated using sealer eluates
from set biomaterials on PDLSCs that EndoSequence® BC Sealer™ and EndoSequence®
BC Sealer™ HiFlow formulations were not cytotoxic, conversely to AH Plus® [77].

2.2.2. Antimicrobial Activity

CSBS’ antimicrobial activity is mostly linked to their ability to increase pH, as pre-
sented before, consecutive to hydroxyl ion releasing. Indeed, a pH increase was highlighted
by many studies, in comparison to conventional sealer formulations [3,13,14,40,78,79]. Un-
like the latter, CSBS induced an alkalization lasting in time, although this property was
sometimes reported as reduced in the case of MTA Fillapex® . Evaluation of CSBS’ antimi-
crobial activity was also widely studied, using various protocols, micro-organism strains,
and types of contact/micro-organism organization. Indeed, using set material sample for a
direct-contact test on planktonic micro-organisms and a biofilm model on dentin, it was
shown that TotalFill BC Sealer® was more efficient against both E. faecalis and C. albicans [80].
In comparison with many other formulations, a fast and significant effectiveness of iRoot
SP® was shown just after mixing against E. faecalis, even after 3 days, conversely to AH
Plus® using a direct-contact test [81]. Regarding the antibacterial effect of CSBS, Candeiro
et al. (2016) found a similar antibacterial effect of EndoSequence® BC Sealer™ and AH
Plus® against E. faecalis using a direct-contact test up to 7 days [69]. Assessment against
multiple bacterial strains in both a planktonic state and in simulated mono-specie biofilms,
it was reported that TotalFill BC Sealer® and AH Plus® possessed antibacterial activity [82].
However, while AH Plus® presented high antibacterial activity against all planktonic and
biofilm bacteria strains during the first day, this property was drastically reduced for longer
times. TotalFill BC Sealer® use showed an antibacterial effect on planktonic strains up to
7 days, while its effect was lower on mono-specie biofilms, especially against S. aureus and
E. faecalis [82]. Using an 8-week-old biofilm of E. faecalis in an infected root model, Bukhari
and Karabucak demonstrated a superior antibacterial effect of EndoSequence® BC Sealer™
after 1 day and up to 2 weeks, in comparison to AH Plus® [83]. Antibacterial property was
also studied depending on final irrigant use by an agar diffusion test and an intratubular
infection model for BioRoot™ RCS, MTA Fillapex® , and AH Plus® against E. faecalis. It
was concluded that the formulations exhibited higher antimicrobial effects after EDTA use
as compared to PBS, and that BioRoot™ RCS exhibited the highest activity [84].
Overall, CSBS presented similar or even higher antimicrobial properties than conven-
tional sealers. However, a lack of standardization for assessment of antimicrobial properties
has been highlighted [85]. Moreover, it must be pointed out that the clinician should rely
on the root canal disinfection/cleaning procedure instead of the antibacterial properties of
endodontic sealers.

2.2.3. Bioactivity
Although a biomaterial can be characterized as biocompatible, its bioactivity qualifi-
cation implies an ability to stimulate metabolic/cellular-specific events, leading to tissue
healing, whether through regenerative step induction, inflammation control, or both. In the
case of endodontic sealers, events such mesenchymal stem cell migration, growth factor
secretion, and cell differentiation are implicated in periapical healing, just as the modula-
Materials 2021, 14, 3965 9 of 21

tion of pro-inflammatory factor cell secretion/expression or immune cells recruitment are

related to periapical inflammation resolution.
Jung et al. (2018) showed in two studies that in comparison to PCS, AH Plus® , and
MTA Fillapex, only the BioRoot™ RCS had a positive influence on cell metabolism of both
PDL cells and osteoblasts [71,86]. Furthermore, human PDLSC activity and migration were
evaluated using a scratch wound healing assay and adhesion to collagen type I with set
sealer eluates of TotalFill BC Sealer® , MTA Fillapex® , and AH Plus® [76]. Results indicated
the most-favorable responses with the use of TotalFill BC Sealer® , while the use of MTA
Fillapex® resulted in the least-favorable responses, even compared to AH Plus® [76]. All
of these previously mentioned cell populations are essential in periapical tissue regen-
eration, and alteration of their metabolism/activity may impact this latter. Evaluating
PDL lipopolysaccharides (LPS)-stimulated fibroblast implication in both regeneration and
inflammation events, it was demonstrated that BioRoot™ RCS, conversely to PCS, did not
alter PDL stem cell migration while controlling immune cell (THP-1 model) migration and
activation. Furthermore, this study highlighted that BioRoot™ RCS induced PDL fibroblast
growth factor (TGF-β1) secretion and reduced pro-inflammatory cytokine (IL-6) secretion
by ELISA [73]. It has also been shown that the use of BioRoot™ RCS did not alter the cell
mesenchymal character and migration ability of human PDLSCs [7]. Moreover, PDL cell
angiogenic/osteogenic growth factor secretions (VEGF, FGF, BMP-1) were shown to be
increased by the use of BioRoot™ RCS extracts [12]. In addition to their secretion, it has
also been shown that the expression of osteogenic factor by murine osteoblast precursor cell
line was increased by EndoSequence® BC Sealer™ and ProRoot ES, using fluorescence and
RT-PCR (DMP-1, ALP), while the use of AH Plus® impaired this osteogenic potential [74].
However, using diluted material extracts of EndoSequence® BC Sealer ™, MTA Fillapex®
and AH Plus® both increased the cell osteogenic potential of an osteoblast cell line after an
LPS-induced inflammation state [87]. Moreover, in addition to an osteogenic potential, it
has also been demonstrated by qPCR that the EndoSequence® BC Sealer™ and HiFlow for-
mulations were able to stimulate human PDLSC mineralization and cementogenic marker
expressions (ALP, CEMP, RUNX2, and CAP), while AH Plus® did not [77]. Concerning
the inflammation process, the effect of iRoot® SP use was studied on macrophage viability,
cytokine expression, and macrophage polarization [88,89]. Indeed, the inflammatory reac-
tion is a complex process, and while often considered to be deleterious, is necessary for the
implementation of the regeneration steps, and macrophage polarization plays an important
role. Indeed, the macrophage M1 phenotype is recognized as pro-inflammatory, while
shifting to the M2 phenotype acts as anti-inflammatory [90]. Zhu et al. demonstrated that
iRoot® SP was not cytotoxic for a model of macrophage (RAW 264.7) and induced both pro-
and anti-inflammatory cytokine expressions (IL-1b, TNF-a, IL-10, IL-12p40). Moreover, use
of this CSBS formulation induced an increase of M1 and M2 macrophage marker expression
and reduced the balance of M1/M2 macrophage phenotypes, indicating that this sealer
could promote healing processes [89]. Close results were obtained by Yuan et al., who
studied iRoot® SP’s effects on the same events after an LPS-induced inflammatory state
simulation. This work also found a potential effect of iRoot® SP on mRNA inflammation
factor expressions and M1/M2 macrophage phenotype balance [88].
Taken together, the whole of these in vitro studies, clearly demonstrated that CSBS,
presented promising biological properties, when compared to conventional sealers. It
may hypothesize that, in addition to an adequate endodontic clinical protocol, CSBS could
promote the healing process in case of apical periodontitis due to their enhanced biocompat-
ibility and certain bioactivity. However, it must be pointed out that additive in formulations
can alter these properties. Indeed, more inconsistent results in the literature were obtained
with MTA Fillapex® formulation. This is often explained by the presence of resinous
compounds of the salicylic type in their formulations and substance leaching [72,91,92],
just as a silicate hydration reaction alteration and reduced or absent calcium hydroxide
formation [25].
Materials 2021, 14, 3965 10 of 21

2.3. Obturation Quality

The main objective of obturation is to prevent leakage and reinfection of the root canal
system [93]; microleakage can occur due to gaps or voids occurrence [94,95]. While the
postoperative radiograph helps in assessing the obturation quality in a clinical approach,
many laboratory methods can value the root canal filling quality in vitro: dye penetration,
dye diffusion, bacterial and endotoxin infiltration, electrochemical, microscopy, or 3D
evaluation [62]. Voids are often investigated because they represent some spaces where
residual bacteria might re-grow and release their byproducts, thus jeopardizing the long-
term success of the root canal treatment [96,97].
A study evaluating apical sealing ability using apical linear dye penetration and
comparing AH Plus® , Endosequence BC® Sealer™, and MTA Fillapex ® showed the lowest
apical leakage value for the SC technique used with the EndoSequence BC® Sealer™ [98].
As already shown in the literature, results for the dye techniques remain contradictory,
inducing a wide variability. An important consideration in relation to dye penetration
studies is that air trapped in voids within the root canal obturation material might interfere
with fluid movement [62,99].
One study evaluated the microleakage of different types of sealer, demonstrating that
the Endosequence BC® Sealer™ group showed the least dye leakage, while the highest
leakage was observed in zinc oxide–eugenol-based sealer [100].
Materials 2021, 14, x FOR PEER REVIEW Nevertheless, many factors may influence voids’ proportion, including the root 11 canal
of 22
filling technique (Figure 3), film thickness, flowability, and wettability.

Figure3.3.Large
Figure Largevoid
voidfollowing
followingroot
rootcanal
canalobturation
obturationwith
withsingle
singlecone
conetechnique.
technique.

Voidincidence
Void incidencehashasbeen
beenreported
reportedto tobe
begreater
greaterwithin
withinovalovalroot
rootcanals,
canals,especially
especially
whenthis
when thisspace
spacewaswasfilled
filledwith
withCHC
CHCandandespecially
especiallywhen
whenusing
usingthetheSCSCtechnique
techniqueor orcold
cold
lateralcompaction
lateral compaction[101,102].
[101,102].Another
Anotherstudy
studyassessed
assessedthe
thefilling
fillingquality
qualityof offive
fiveobturation
obturation
techniquesin
techniques inoval-shaped
oval-shapedrootrootcanals
canalsby
byusing
usingan
anoptical
opticalnumeric
numericmicroscope,
microscope,SEM, SEM,and
and
energy-dispersive X-rays
energy-dispersive X-rays (EDX)
(EDX) [103].
[103]. This
This study
study investigated
investigated the the proportions
proportions of of gutta-
gutta-
percha-filledareas,
percha-filled areas,sealer-filled
sealer-filledareas,
areas,void
voidareas,
areas,and
andthe
thesealer/gutta
sealer/guttatagstagsinto
intodentinal
dentinal
tubules.
tubules.Obturation
Obturationquality
qualitywas
wasoverall better
overall when
better whenusing a warm
using a warmgutta-percha
gutta-perchaobturation
obtura-
technique compared
tion technique to the use
compared of the
to the useSC
of technique, regardless
the SC technique, of the type
regardless of of
thesealer.
type ofA recent
sealer.
study based on confocal microscopic evaluation showed that the use
A recent study based on confocal microscopic evaluation showed that the use of warm of warm vertical
compaction enhanced
vertical compaction the penetration
enhanced of CSBS of
the penetration into the into
CSBS dentinal tubules tubules
the dentinal in comparison
in com-
parison with the SC technique [104]. The inherent limitations of the SC technique even
using CSBS was demonstrated in a micro-CT study [105].
Micro-CT has been suggested to be the most reliable technique to investigate the fill-
ing quality differentiating gutta-percha, sealer, and voids. This technique allows the eval-
uation of void/porosity incidence (apical, middle, or coronal thirds), and the identification
Materials 2021, 14, 3965 11 of 21

with the SC technique [104]. The inherent limitations of the SC technique even using CSBS
was demonstrated in a micro-CT study [105].
Micro-CT has been suggested to be the most reliable technique to investigate the filling
quality differentiating gutta-percha, sealer, and voids. This technique allows the evaluation
of void/porosity incidence (apical, middle, or coronal thirds), and the identification of their
type (internal, external, or combined) [106,107]. A study assessed the remaining voids after
obturation between Endosequence® BC Sealer™ and AH Plus® using the SC technique.
EndoSequence® BC Sealer™ showed a lower ratio of voids compared to AH Plus® in the
apical third, but it was highlighted by the authors that this difference was likely due to root
canal anatomy variations [108]. A recent study showed that the proportion of open and
closed porosity can change over time [107]. Initially, significantly greater open and total
porosity were found for MTA Fillapex® than for AH Plus® . After 6 months, the percentage
of open and total porosity increased in BioRoot™ RCS and MTA Fillapex® , and decreased
in AH Plus® and Endosequence® BC Sealer™. These findings were explained by the greater
solubility of BioRoot™ RCS and MTA Fillapex® compared to AH Plus® . The better ability
of EndoSequence® BC Sealer™ to create apatite formation compared to BioRoot™ RCS
might explain the reduction of porosity for EndoSequence® BC Sealer™ 6 months after
storage [107].
When compared to conventional sealers, CSBS have overall shown comparable results
when evaluating void incidence using micro-CT [109]. However, void incidence should be
always put in perspective with the root canal anatomy and the obturation technique used.

2.4. Retreatability
Non-surgical retreatment implies removal of root canal filling material in order to
re-establish apical patency, then clean and fill the entire root canal system (AAE 2012).
Therefore, retreatability is one of the requested properties of filling materials [110,111].
Currently there is no technique allowing complete removal of filling materials from a root
canal system [111]. In addition, several factors may influence the retreatability, such as the
filling technique implemented, and the type of sealer used with gutta-percha [110,111].
CSBS are known to be hard upon setting [112] and to create hydroxyapatite crystals
upon their interface with dentin [113]. In addition to that, they are capable of pene-
trating into the dentinal tubule. These properties may render retreatment procedures
difficult [114]. To study removal of filling materials, different methods have been used such
as micro-computed tomography (micro-CT), cone-beam computed tomography (CBCT),
radiography, tooth splitting and direct visualization by SEM, confocal microscopy, stere-
omicroscopy or digital cameras, and rendering the teeth transparent [110,114–117]. As
it has already shown to be reliable for evaluation of the quality of the root canal filling,
micro-CT is non-invasive and allows for the comparison of the remaining volume of the
filling material to the initial volume. In addition to visualizing and measuring the remain-
ing filling material, SEM and confocal microscopy can also be used to assess the degree
of penetration of the sealer inside dentinal tubules, or to quantify the number of open
tubules [114,116].
Ersev et al. (2012) compared the retreatability of four root canal sealers (Hybrid Root
SEAL, EndoSequence® BCSealer™, the Activ GP system, and AH Plus® ) and found no
significant differences between the different sealers, or between the techniques used [118].
As demonstrated in many investigations, no technique allowed the complete removal of
the filling material. Simsek et al. (2014) compared the number of opened tubules using
SEM after the removal of iRoot® SP, AH Plus® , and MM Seal® in straight premolars filled
with the lateral compaction technique after the use of R-endo rotary instruments or ESI
ultrasonic tips. Likewise, no group showed complete removal of the filling material, with
greatest leftover in the apical third [116].
Kim et al. (2015) also did not find any significant differences between Endosequence®
BC Sealer™ and AH Plus® when comparing the amount of residual material using SEM
analysis [114]. According to Uzunoglu et al. (2015), more remaining filling material was
Materials 2021, 14, 3965 12 of 21

observed following the SC technique with iRoot® SP compared to SC with AH-26® or

lateral compaction with AH-26® (DeTrey, Dentsply Maillefer, USA), when assessed with
SEM [110]. In addition, Suk et al. (2017) did not find any significant differences in the
removability of EndoSequence® BC Sealer™ and AH Plus® . In this study, MTA Fillapex®
was found to be the easiest to remove [117].
Hess et al. (2011) noted better removability of AH Plus® compared to Endosequence®
BC Sealer™ in canals of less than 20 degrees of curvature [119]. More remnants of this CSBS
were found in the apical third upon SEM analysis, and patency was not re-established in
20% of samples with BC Sealer and master cone to the WL, or in 70% of samples with BC
Sealer and master cone short of the WL. Agrafioti et al. (2015) compared the retreatability
of Total Fill® BC Sealer™, MTA Fillapex® , and AH Plus® in straight canals [113]. Authors
have demonstrated that WL and apical patency were re-established in 100% of cases, when
the gutta-percha cones were placed at WL. Oltra et al. (2017) compared the retreatability of
BC Sealer and AH Plus® using micro-CT imaging and found that the latter was associated
with less residual filling materials, and that the use of chloroform may help BC Sealer
removal [120]. On the other hand, Donnermeyer et al. (2018) found that AH Plus® was
associated with more remnants when compared to Bio Root™ RCS, MTA Fillapex® , and
Endo CPM (Egeo, Buenos Aires, Argentina) [112].
Contradicting results between studies [112,120] could be related to the application
of different methodologies, especially the length of adjustment of the gutta-percha cone
and the dental sample anatomy. In the study conducted by Hess et al. (2011), gutta-percha
cones were intentionally placed short of the apical foramen. It must be pointed out that
this method represented the most realistic scenario of a non-surgical retreatment. This
could clearly compromise retreatment outcome [119]. In other studies, gutta-percha cones
were placed at full WL This different protocol could strongly influence the ability to re-
establish the apical patency after removal of root canal filling material. Indeed, with the
gutta-percha cone being introduced to the full working length, the apical patency could
easily be re-established following easy removal of the latter. However, these situations
did not correspond to the vast majority of retreatment indications. Indeed, it is well
known that apical periodontitis is usually diagnosed in the case of poor quality and short
obturation [121].
On the other hand, root canal anatomy, such as canal curvature and cross-section, may
also impact retreatability. Hess et al. (2011) used mesial canals of mandibular molars, while
in Agrafioti et al. (2015), straight canals from anterior teeth were evaluated [113,119].
In addition, the obturation technique used can influence the results. Manufacturers
usually recommend CSBS with the SC technique, and some studies demonstrated that
the use of these sealers with continuous wave condensation may decrease their bond
strength [56]. This may explain the absence of differences between CSBS and resin-based
sealers in the studies conducted by Agrafioti et al. (2015) and Kim et al, (2015) [113,114].
Contradictory results were also obtained regarding the retreatment time. Simsek et al.
(2014) did not find a statistical difference in the time to reach WL when removing iRoot®
SP, MM Seal, and AH Plus® [116]. Similar findings were obtained by Kim et al. (2015)
when comparing time for removal of EndoSequence® BC Sealer™ and AH Plus® [114].
Uzunoglu et al. (2015) reported a faster retreatment when the filling material consisted of
gutta-percha and MTA Fillapex® compared to AH Plus® and iRoot® SP, which showed
similar results [110]. Donnermeyer et al. (2018) found that the removal of CSBS (BioRoot™
RCS and Endo CPM) was faster than for AH Plus® [112].
In conclusion, most ex vivo studies showed possible CSBS removal, and an ability
to regain apical patency in the majority of cases. However, methodological bias could be
observed in many studies, and further studies better simulating retreatment indications
and conditions are needed.
Materials 2021, 14, 3965 13 of 21

3. A Proposal for Clinical Perspectives on CSBS with Cold Hydraulic Condensation

3.1. Root Canal Anatomy
CHC and cold lateral compaction are known to increase void occurrence compared to
warm gutta-percha obturation techniques, especially in large and oval canals regardless of
the type of sealer [103,105,122,123]. However, in case of narrow, long, and curved canals,
the use of warm vertical compaction can be questionable, since penetration of the heat
plugger at the appropriate level (4 mm short of the working length) can sometimes be
impossible. Thus, the gutta-percha is not heated and melted in the apical third, and the
obturation of this area behaves as a SC technique [124]. Using CHC with CSBS in these
types of anatomy makes root canal obturation easier and faster while taking advantage of
CSBS’ physico-chemical and biological properties.

3.2. Operative Accessibility

It is common sense to highlight that CHC and CSBS should make the obturation
procedure easier and faster when dealing with a restricted access (limited mouth open-
ing/posterior teeth) compared to the use of thermoplasticized gutta-percha obturation
Materials 2021, 14, x FOR PEER REVIEW 14 of 22
techniques. Indeed, by using CHC, the technical difficulties are limited to the intracanal
sealer placement and the insertion of the gutta-percha cones (Figure 4).

Figure 4. Example
Exampleofofindication
indicationofofthe
thesingle-cone technique
single-cone with
technique CSBS.
with CSBS.(A)(A)
Preoperative periapical
Preoperative radiograph
periapical of aof
radiograph ne-
a
crotic maxillary molar with long roots, sinus proximity, and patient’s limited mouth opening. (B) Postoperative periapical
necrotic maxillary molar with long roots, sinus proximity, and patient’s limited mouth opening. (B) Postoperative periapical
radiograph of
radiograph of root
root canal
canal obturation
obturation using
using CSBS.
CSBS.

Biological Aspects
3.3. Biological Aspects
mentioned previously, their biological properties are the main advantages of
As mentioned
CSBS over conventional sealers. A A recent international survey showed that this has been
claimed to be the most-frequent
claimed to be the most-frequent reason reasonto to justify
justify their
their clinical
clinical useuse
[22].[22].
Based Based
on theonfind-
the
findings
ings of inofvitro
in vitro studies,
studies, CSBS
CSBS antibacterial
antibacterial activityand
activity andbiomineralization
biomineralization ability
ability might
the potential
have the potential totostimulate
stimulateand
andimprove
improvethe theperiapical
periapical healing,
healing, andand thus
thus should
should be
be suitable
suitable in case
in the the case of apical
of apical periodontitis.
periodontitis. Likewise,
Likewise, CSBS alkalization
CSBS alkalization ability
ability and and
calcium
hydroxide formation might make them interesting to use in the case of external inflam-
matory root resorptions.
Finally, even if sealer extrusion in the periapical area is not suitable and should re-
main inadvertent, a sealer “puff” during obturation can be difficult to predict and control
[125]. Taking into consideration better CSBS biological properties over the ones of con-
Materials 2021, 14, 3965 14 of 21

calcium hydroxide formation might make them interesting to use in the case of external
inflammatory root resorptions.
Finally, even if sealer extrusion in the periapical area is not suitable and should
remain inadvertent, a sealer “puff” during obturation can be difficult to predict and
control [125]. Taking into consideration better CSBS biological properties over the ones of
conventional sealers highlighted in this narrative review, CSBS might be preferable to use
in the following situations:
• Connection between the roots and the maxillary sinus, especially for immunocompro-
mised patients for whom zinc oxide–eugenol-based and formaldehyde-based sealers
are not recommended [22].
• Connection between the roots and inferior alveolar nerve: CSBS are more biocompati-
ble, and their use with CHC avoids thermal nerve injuries.
• Middle or apical root canal perforations, consequences of a false canal: the use of
CSBS with CHC allows the filling of the root canal and the perforation at the same
time while also taking advantage of their biological properties.
• Patients with high risks of osteonecrosis connected to treatments such as radiotherapy
or anti-resorptive drugs such as bisphosphonates, because it is suitable to reduce bone
aggression factors in these situations.
However, it must be highlighted that regarding the biological aspects, a direct trans-
lation from the findings of in vitro studies to clinical outcome is not relevant. Indeed,
the healing of the periapical area is not only related to the sealer’s choice, but involves
numerous complex mechanisms, including the patient’s immune system [126].

4. Clinical Application of CSBS

4.1. Can CSBS Be Used with Any Type of Gutta-Percha?
Based on our review of the literature investigating the interface between gutta-percha
and CSBS, there is no available evidence supporting the use of specific pre-impregnated
gutta-percha cones with CSBS. However, a different interface quality between CSBS and the
gutta-percha cone might be observed, depending on the type of gutta-percha and related
chemical composition [22,57,127].

4.2. Do CSBS Usage Impact the Final Irrigation Protocol and the Root Canal Drying Technique?
Intracanal moisture negatively influences the setting process of conventional sealers
and their adhesion to dentinal walls [128]. Unlike them, CSBS need water to initiate the
hydration reaction that conditions their setting process, and also their biological proper-
ties [4]. According to the manufacturers, the dentinal tubules’ moisture initiates the setting
of premixed formulations [4]. Therefore, intracanal dentin desiccation should be avoided,
leading to gently dry the root canal before obturation [129]. This procedure is difficult to
control, as it was shown in restorative dentistry in a wet-bonding procedure [130]. The
use of intracanal micro-suction to empty the canal before the use of one sterile paper point
could help preventing over-dehydration [129]. On this basis, a final rinse with ethanol is
contra-indicated when using CSBS [22,129].
Finally, since the canal has to remain slightly wet, potential interactions between the
final irrigant and CSBS should be taken into account. Indeed, several studies showed that
most of the available irrigants (NaOCl, CHX, EDTA) may negatively affect CSBS [52,84,131].
So far, the clinical significance of such interactions remains unclear. However, it seems
suitable to perform a final rinse with sterile water to flush out the last irrigant before root
canal drying.

4.3. How to Reduce Voids Occurrence When Using CSBS with CHC?
As mentioned previously, the presence of open porosity occurring at the interface
between the sealer and dentinal wall/gutta-percha may constitute a space for residual
micro-organisms to regrow and leak toward the periapical area [107,132].
Materials 2021, 14, 3965 15 of 21

SC obturation induces a higher void ratio compared to warm obturation techniques,

especially in oval or wide root canals [103]. However, as reported in the literature, all
the filling techniques investigated are never “void-free” regardless of the type of sealer
used [133,134]. When dealing with CHC, especially the SC technique, more emphasis is
put on the sealer than the gutta-percha (sealer-based obturation concept). Although the
intracanal sealer placement technique might impact void incidence, the latter is rarely
specified in most publications. Many techniques can be used to place CSBS into the root
canal system, depending on the formulation and the anatomy:
• Coating the master cone with CSBS followed by its slow insertion to the full working
length. This technique might be insufficient when dealing with oval or wide canals.
Accessory cones can also be used to complete the sealer distribution.
• Lentulo spiral usage at low speed (around 700–800 rpm) or flexible injection tip before
master cone insertion.
Applying sonic/ultrasonic activation and other sealer activation/agitation procedures
may also contribute to improve CSBS distribution in the root canal space [135], but the
level of evidence on these points is still weak.

4.4. Can CSBS Be Used with Thermoplasticized Gutta-Percha Obturation Techniques?

As stated previously, the SC technique being associated with greater void incidence,
using CSBS with thermoplasticized gutta-percha obturation could make sense, as this
would combine the advantages of these techniques already used by many endodontic
specialists with the improved properties of CSBS. However, this leads us to question the
impact of heat on CSBS’ properties, which have been addressed in several studies showing
different findings according to the formulations tested [25,37,136,137]. A temperature rise
(especially above 100 ◦ C) may lead to a change in CSBS’ physical properties, especially
their flowability, setting time, and adhesion to dentin walls [104,136]. Based on the avail-
able knowledge, Endosequence® BC Sealer™ HiFlow® and EndoSequence® BC Sealer™
formulations could be used with heat [104], but not all CSBS can. For instance, BioRoot™
RCS is contra-indicated with warm gutta-percha obturation [25,37]. Therefore, there is a
need for additional studies to clarify the impact of heat on each CSBS formulation. These
considerations should also take into account the real temperature delivered by the heater
plugger, which has been reported to be much lower than the one displayed on the device
screen [137]. Finally, conventional sealers have also been reported to be negatively im-
pacted by heat application in laboratory studies [37], while they have been used widely for
decades with thermoplasticized gutta-percha obturation techniques and with satisfactory
clinical outcome. This points out the gap existing between the findings of in vitro studies
and the complexity of parameters involved in the clinical outcome.

4.5. Does Use of CSBS Make Non-Surgical Retreatment More Difficult?

The literature showed that CSBS may be removed with difficulty in the case of retreat-
ments [119]. No specific solvent is available for removing CSBS during retreatments, even if
formic acid and chloroform may help the endodontist. As stated previously, studies assess-
ing CSBS retreatability have shown that apical patency could be properly achieved when
the obturation of the previous treatment reached the full working length [112,118,138,139].
Nevertheless, non-surgical retreatments are mainly indicated when the obturation is short.
Good flowability of CSBS may result in CSBS penetration beyond the gutta-percha cone tip.
The presence of CSBS only and its hardness may make apical patency much more challeng-
ing to achieve, especially in curved root canals [119] blocking the access to the apical third
and resulting in possible procedural errors such as ledges. Furthermore, retreatments also
aim to remove all previous materials and disinfect the root canal system before filling it
again. Nevertheless, the complete removal of the obturation material remains impossible,
and all the techniques shown in the literature were only able to partially remove CSBS
from the root canal [114,117] as demonstrated with any filling material.
Materials 2021, 14, 3965 16 of 21

5. Conclusions
This narrative review aimed to discuss the properties of CSBS and their clinical impli-
cations, and to propose rational indications based on the current knowledge. This work
may help practitioners in selecting the appropriate sealer and pave the way for reasoned
CSBS usage. CSBS have shown good all-around performance when compared to conven-
tional sealers, but significant differences could be observed between the different CSBS
formulations. Their particularity remains in their interesting biological properties, which
were proven to be better than those of conventional sealers. However, the clinical impact
of CSBS solubility must be clarified in the future. Likewise, available CSBS formulations
can present specificities that have to be considered by the practitioner for proper clinical
usage. Finally, the usual clinical endodontic protocol has to be slightly revised to consider
CSBS specific behavior.

Author Contributions: Conceptualization, G.S., F.B. and C.Z.; methodology, F.B., C.Z. and V.N.;
validation, F.B., C.Z. and V.N.; literature search and data extraction, G.S., C.Z. and F.B.; writing—
original draft preparation, G.S., F.B. and C.Z.; writing—review and editing, G.S., C.Z., S.P., T.G., V.N.
and F.B.; supervision, C.Z. and F.B.; funding acquisition, G.S. and C.Z. All authors have read and
agreed to the published version of the manuscript.
Funding: This research was funded by the University of Saint-Joseph, Beirut, Lebanon.
Institutional Review Board Statement: Not Applicable.
Informed Consent Statement: Not Applicable.
Data Availability Statement: No new data were created or analyzed in this study. Data sharing is
not applicable to this article.
Conflicts of Interest: The authors have stated explicitly that there are no conflicts of interest in
connection with this article.

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