doi:10.1111/iej.

13449

REVIEW
Efficacy of direct pulp capping for management of
cariously exposed pulps in permanent teeth: a
systematic review and meta-analysis

S. Cushley1, H. F. Duncan2 , M. J. Lappin1, P. Chua1, A. D. Elamin1, M. Clarke1 &

I. A. El-Karim1
1
School of Medicine Dentistry and Biomedical Sciences, Queen’s University Belfast, Belfast, UK; and 2Division of Restorative
Dentistry & Periodontology, Dublin Dental University Hospital, Trinity College Dublin, University of Dublin, Dublin, Ireland

Abstract checklist. Meta-analysis on combined clinical/radio-

Cushley S, Duncan HF, Lappin MJ, Chua P, Elamin
AD, Clarke M, El-Karim IA. Efficacy of direct pulp
capping for management of cariously exposed pulps in
permanent teeth: a systematic review and meta-analysis.
International Endodontic Journal, 54, 556–571, 2021.
Background The outcome of vital pulp treatment
after carious pulp exposure is multifactorial and
related to the procedure, biomaterial and pre-opera-
tive pulpal diagnosis.
Objectives To conduct a systematic review and
meta-analysis determining the outcome of direct pulp
capping (DPC) in mature permanent teeth with a car-
iously exposed pulp and a clinical diagnosis of reversi-
ble pulpitis, and ascertain whether the capping
material influences the outcome.
Methods Sources: MEDLINE Ovid-SP, Cochrane
Central Register of Controlled Trials (CENTRAL),
International Clinical Trials Registry Platform
(ICTRP), ClinicalTrials.gov, Embase and Web of
Science until April 2020. Inclusion: Prospective, ret-
rospective cohort studies and randomized trials inves-
tigating DPC outcome or comparing different capping
materials after carious pulp exposure. Exclusion: Pri-
mary teeth, mechanical, traumatic or not specified
pulp exposure, teeth with irreversible pulpitis or no
pulpal diagnosis. Risk of bias assessed using Cochrane
and modified Downs and Black quality assessment
graphic outcome was performed using a random
effect model. Success was defined as absence of signs
and symptoms of irreversible pulpitis, apical periodon-
titis or loss of pulp vitality.
Results Quality assessment highlighted four non-
randomized studies to be of fair and five of poor qual-
ity. Four randomized trials had a high risk of bias.
The pooled success rate differed based on material
and follow-up. Calcium hydroxide success rate was
74% at 6-months, 65% at 1-year, 59% at 2–3 years
and 56% at 4–5 years. Mineral trioxide aggregate
(MTA) success was 91%, 86%, 84% and 81% at the
same time points. Biodentine success was 96% at
6-months, 86% at 1 year and 86% at 2–3 years. The
meta-analysis revealed MTA had better success than
calcium hydroxide at 1-year (OR 2.66, 95% CI; 1.46-
4.84, P = 0.001) and 2- to 3-year follow-up (OR
2.21, 95% CI; 1.42–3.44, P = 0.0004). There was no
difference between MTA and Biodentine.
Discussion These results were based on poor
methodological quality studies. The effect size for of
MTA vs Ca(OH)2, although modest, was consistent
with narrow CI.
Conclusions Low-quality evidence suggests a high
success rate for direct pulp capping in teeth with cari-
ously exposed pulps with better long-term outcomes
for MTA and Biodentine compared with calcium
hydroxide.

Correspondence: Ikhlas A. El Karim, The Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry
and Biomedical Sciences, Queen’s University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK (Tel.: +442890976026; Email:
i.elkarim@qub.ac.uk).

556 International Endodontic Journal, 54, 556–571, 2021 © 2020 International Endodontic Journal. Published by John Wiley & Sons Ltd

Keywords: direct pulp capping, exposed pulp, deep
caries, pulpitis, vital pulp treatment.
Introduction
Preservation of pulp vitality is a critical factor in
long-term tooth survival (Caplan et al. 2005). The
vitality of the dental pulp can be compromised by the
presence of a deep carious lesion and by its subse-
quent management (Ricketts et al. 2013); therefore,
treatment options aimed at preserving pulp vitality
are recommended (Innes et al. 2016, ESE 2019). Tra-
ditionally, such lesions are treated with complete
(non-selective) caries removal, but emerging evidence
suggests that risk of pulp exposure associated with
complete caries removal could be avoided by adopting
more conservative, partial (selective) caries removal
approaches (Bjørndal et al. 2010, Schwendicke et al.
2016). Despite advances in the understanding of the
effects of selective caries removal in managing deep
carious lesions (Banerjee et al. 2017, Bjørndal et al.
2019), non-selective caries removal techniques
remain common (Oen et al. 2007, Stangvaltaite et al.
2013, Schwendicke et al. 2017). It is evident from
these studies that non-selective caries removal and
pulp exposure are still not considered overtreatment
by many clinicians where removal of all caries is rou-
tine practice. Therefore, carious exposure in deep
lesions is a common occurrence in clinical practice in
cases with no or mild symptoms and may still be
inevitable even when a selective caries removal
approach is adopted (Maltz et al. 2012, Hoefler et al.
2016).
There are several treatment options available for
carious exposure, varying from conservative mini-
mally invasive vital pulp treatments (VPT), including
direct pulp capping (DPC), partial and complete pulpo-
tomy to the more invasive pulpectomy and root canal
treatment (ESE 2019). Although root canal treatment
is the traditional treatment of choice for the cariously
exposed pulps, it is destructive and a technically
demanding procedure (ESE 2019). Pulpotomies are
less invasive than root canal treatment and have high
success rates in pathologically exposed pulps particu-
larly when the clinical diagnosis was reversible pulpi-
tis (Alqaderi et al. 2016, Elmsmari et al. 2019,
Cushley et al. 2019). DPC is a more conservative
treatment strategy, based on the premise that a bio-
logically active material placed in direct contact with
© 2020 International Endodontic Journal. Published by John Wiley & Sons Ltd
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Cushley et al. Direct pulp capping for cariously exposed pulps
Received 25 August 2020; accepted 17 November 2020
the pulp wound can determine the pulpal response
and result in the development of a reparative hard tis-
sue bridge to preserve pulp vitality (Fransson 2012,
Fransson et al. 2016). The established technique has
been the subject of multiple studies over several dec-
ades, with earlier studies in which bacterial contami-
nation could not be controlled reporting low success
rates and casting doubt on the clinical utility of the
technique (Aguilar & Linsuwanont 2011). Recently,
however, studies using more biocompatible materials
with a good sealing ability such as mineral trioxide
aggregate (MTA), Biodentine (Septodont, Saint-Maur-
des-Foss
es, France) and other calcium silicate cements
have been associated with higher success rates in
traumatically as well as cariously exposed teeth (Nair
et al. 2009, Li et al. 2015).
Clinical and radiographic success of DPC in young
permanent teeth with carious exposures was reported
to be high (Brod
en et al. 2016), and the procedure
has been suggested as a cost-effective alternative to
root canal treatment in children and young adults in
modelling studies (Schwendicke & Stolpe 2014,
Brod
en et al. 2019).To date, many studies have evalu-
ated the outcome of DPC using various materials and
for several clinical indications. Previous systematic
reviews on the outcome of DPC compiled evidence
from carious as well as non-carious exposures and
used different outcomes (Li et al. 2015, Brod
en et al.
2016, Paula et al. 2018). The first of these DPC sys-
tematic reviews (Li et al. 2015) focused on compar-
isons between Mineral Trioxide Aggregate (MTA) and
calcium hydroxide in ‘sound’ teeth, including teeth
with experimental pulp capping and ex vivo histologi-
cal analysis (Nair et al. 2009). This has limited rele-
vance to clinical practice because DPC is generally
carried out after caries exposure (Bjørndal et al.
2019). The second systematic review (Brod
en et al.
2016) excluded patients over 20 years of age and did
not include pulpal diagnosis as a criteria for inclusion
so it was unable to evaluate the critical influence of
root formation and pulpitis in DPC (Al-Hiyasat et al.
2006). The most recent of the three systematic
reviews also did not select studies on pulpal diagnosis
and also included partial pulpotomy as well as DPC in
the inclusion criteria (Paula et al. 2018). To improve
on this, a more focussed PICO question was planned
International Endodontic Journal, 54, 556–571, 2021 557

Direct pulp capping for cariously exposed pulps Cushley et al.
for this systematic review, specifically investigating
only DPC, limited to teeth with a clear pulpal diagno-
sis of reversible pulpitis and restricted to carious expo-
sure in mature permanent teeth. This is the first
systematic review reporting exclusively on the out-
come of DPC of the cariously exposed pulps of perma-
nent teeth and using clinical outcomes (clinical and
radiographic assessment) that are directly measurable
in clinical practice as recommend by the ESE position
statement on the management of deep caries and
exposed pulp (ESE 2019).
This review aims to provide unbiased, good quality
evidence on the effects of DPC for treating permanent
teeth with deep caries and the exposed pulp. It has
two aims:
1. To determine the success, clinically and radio-
graphically after at least 12 months, of DPC in
permanent teeth with cariously exposed pulps
and a diagnosis of reversible pulpitis.
2. To determine whether the choice of pulp capping
material influences the outcome of DPC in these
teeth.
Materials and methods
This systematic review is reported using the PRISMA
guidelines (Moher et al. 2009) and the PICO frame-
work to address the following clinical questions: ‘Is
direct pulp capping a clinically effective treatment for
cariously exposed pulps with a diagnosis of reversible
pulpitis and does success differ with different pulp
capping materials?’ The review was registered in
PROSPERO (CRD42020179136).
Information sources and search strategy
Electronic searches: Electronic database searches were
conducted using a combination of key search words
(pulp capping, pulpitis, caries, success rate, calcium
hydroxide, Biodentine, MTA and permanent teeth).
The MeSH search items and search strategy
(Table S1) were developed for the MEDLINE search
and adopted for other electronic databases. The fol-
lowing databases were searched, until April 2020:
MEDLINE (1960 to present, in-process and other non-
indexed citations, Ovid SP), Cochrane Central Register
of Controlled Trials (CENTRAL), International Clinical
Trials Registry Platform (ICTRP) and ClinicalTrials.-
gov, Embase (1960 to present) and Web of Science.
To ensure literature saturation, reference lists of
included studies and reviews were checked for eligible
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studies. The Open SIGLE database was also searched
for grey literature and to identify additional studies
not indexed in the other databases. Studies published
in English only were included.
Study selection process
The type of participants had mature permanent teeth
with deep caries and an exposed pulp with a clearly
stated pulpal diagnosis of normal or reversible pulpi-
tis. The intervention was DPC of a cariously exposed
pulp using either one material or comparing two or
more capping materials. The primary outcome was
the success of DPC after at least one-year follow-up
measured by (a) absence of clinical symptoms of spon-
taneous pain, tenderness to percussion or palpation,
(b) no radiographic evidence of periapical changes
indicative of apical periodontitis and (c) positive
response to pulp sensibility tests.
Exclusion criteria
Primary teeth; case reports, expert opinions or
reviews; studies in which exposure was in unrestored,
sound teeth; cases of pulp exposure caused by trauma
or mechanical exposure; teeth with immature apices;
studies which, did not specify whether the pulp was
cariously exposed, teeth with irreversible pulpitis or
where pulpal diagnosis was not provided and prospec-
tive studies on which the dropout rate was higher
than 20% (Strauss et al. 2019).
The PRISMA flow chart (Fig. 1) illustrates the
selection process. The screening and assessment of eli-
gibility criteria involved the screening of titles and
abstracts by three assessors independently (SC, IEK,
HD). The full text was obtained for all studies that
met the inclusion criteria or when the abstract did
not contain enough information to apply the selection
criteria. Any disagreement was resolved by discussion.
Full-text articles were assessed for quality and inclu-
sion in a possible meta-analysis by three assessors
independently.
Quality assessment of included studies
Three assessors (SC, IEK, ML) independently assessed
the risk of bias for each included study. The method-
ological quality of non-randomized studies was
assessed using modified Downs and Black quality
assessment checklist (Downs & Black 1998). Domains
covered by this scale included reporting, external and
internal validity (bias and confounding) and power.
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559
Cushley et al. Direct pulp capping for cariously exposed pulps

International Endodontic Journal, 54, 556–571, 2021

© 2020 International Endodontic Journal. Published by John Wiley & Sons Ltd
Figure 1 Review PRISMA Flow Diagram.

Direct pulp capping for cariously exposed pulps Cushley et al.
Each domain was assigned a score, and the total score
for each study is provided. Risk of bias in randomized
trials was assessed using the criteria outlined in the
Cochrane Handbook for Systematic Reviews of Inter-
ventions (Higgins & Green 2011). A high or low risk of
bias was assigned to an individual study when there
was evidence or absence of the following variables:
selection bias, detailed allocation information, perfor-
mance bias, detection details, attrition details, selective
reporting bias or ‘other bias’ that did not fall into any
of the listed categories. Unclear risk of bias was
assigned when there was insufficient information to
permit judgment of low or high risk. The evidence level
for each of the included studies was graded using the
Oxford Centre for Evidence-Based Medicine recommen-
dation (http://www.cebm.net/oxford-centre-evidence-
based-medicine-levels-evidence-march-2009/) (Oxford
Centre for Evidence-Based Medicine 2009).
Data collection/extraction process
Data were extracted by two authors independently (SC,
IEK) and included type of study, number and demo-
graphics of participants, diagnosis, intervention, cap-
ping material, follow-up period, the number lost to
follow-up, funding source, location of the study and
outcomes. The final data to be included were agreed by
three authors (SC, IEK, HD), and any differences of
opinion were resolved by further discussion. In studies
reporting mixed data (e.g. reversible and irreversible
pulpitis; traumatic and mechanical carious exposure;
mature and immature teeth), whenever possible, only
data that were relevant to the inclusion criteria were
extracted and if it was not possible to disaggregate data
in this way, the study was excluded. The extracted data
were checked for accuracy by two authors (IEK, HD).
Data synthesis
Data entry and synthesis was carried out on Review
Manager, Version 5.3. (The Nordic Cochrane Centre,
The Cochrane Collaboration, Copenhagen, Denmark).
Heterogeneity was assessed by calculating the I2
statistic and defined as low I2 25%: moderate I2 50%:
and high I2 75% (Higgins et al. 2003). The success
rate for DPC was calculated for each study by dividing
the number of successful cases by the total number of
cases. Meta-analysis using the random effect model
was performed when heterogeneity was acceptable or
moderate, and odds ratios with 95% confidence inter-
vals (CI) were calculated. Subgroup analysis was
560 International Endodontic Journal, 54, 556–571, 2021
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performed to determine if the study design influenced
the outcome. To evaluate the effect of the results of
the different studies in the pooled outcome, a sensitiv-
ity analysis was performed by omitting each study
from the meta-analysis. Results were presented in
tables and a forest plot, and bias associated with
study size (e.g. publication bias) was evaluated in a
funnel plot.
Results
Selected studies
Details of the study selection process are outlined in
Fig. 1. Thirty-eight, full-text articles were assessed for
eligibility and 24 of these were excluded. The reasons
for exclusion are explained in Table 1. The 14 studies
that met the inclusion criteria are five randomized tri-
als(Bjørndal et al. 2010, Kundzina et al. 2017, Awaw-
deh et al. 2018, Parinyaprom et al 2018, Suhag et al.
2019), five non-randomized comparative studies
(Mente et al. 2010, 2014, Cho et al. 2013, Linu et al.
2017, C
alıs
kan & G€
uneri 2017) and four single-arm
prospective studies (Barthel et al. 2000, Farsi et al.
2006, Bogen et al. 2008, Kusumvalli et al. 2019).
Details of the included studies are outlined in Table 2
and those of the study populations in Table 3.
Quality assessment of included studies
The quality assessment of non-randomized studies
was determined using the modified Downs and Black
checklist (Table S2). These revealed five studies to be
of fair quality, and the remaining were assessed as
being of poor quality. Risk of bias assessment of the
randomized trials provided evidence of a high risk of
bias, particularly on blinding of operators (perfor-
mance bias) and outcome assessors (detection bias)
(Figs 2 and 3). There was no evidence of publication
bias with the studies investigating Ca(OH)2 versus
MTA as seen in the funnel plot Fig. S1(a); however,
publication bias exists in studies comparing MTA to
Biodentine Fig. S1(b).
Overall success rates for DPC
All the included studies reported clinical and radio-
graphic success of DPC based on the definition of suc-
cess described in the methods section. The success
rate for each study was calculated by dividing the
number of teeth considered successful by the total
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Cushley et al. Direct pulp capping for cariously exposed pulps

Table 1 Excluded studies and reasons for exclusion 55% for calcium hydroxide and 83% for MTA. At 2–
Number
3 years, it was increased to 62% for calcium hydrox-
of ide and 88% for MTA (Table S3A,B).
Reason for exclusion articles Author, year

Review 1 Asgary et al. 2013 Calcium hydroxide versus MTA as pulp capping
Article unavailable 1 Haskell et al. 1978
material
Study inconsistent with 9 Asgary 2013, Santucci
SR criteria 1999, Oz et al. 2019, To compare the success of DPC of calcium hydroxide
Vural et al. 2017, Katge
with MTA, a meta-analysis was performed at three
et al. 2017, Freitas
et al. 2014, Fitzgerald
follow-up periods, using data from both the random-
and Heys 1991, Miles ized and the non-randomized comparative studies. As
et al. 2010, Harms shown in Fig. 2, there is no significant difference in
et al. 2019 the success rate of calcium hydroxide and MTA at
Methodology 1 Hilton et al. 2013
6 months, but MTA performed better than calcium
Data clarity prevents 3 Matsuo et al. 1996,
data extraction Jang et al. 2015, Lipski
hydroxide at 12 months (OR 2.66, 95% CI; 1.46–
et al. 2018 4.84, P = 0.001) and 2–3 years (OR 2.21, 95% CI;
Data clarity prevents 3 Willerhausen et al. 1.42–3.44, P = 0.0004). Subgroup analysis demon-
data extraction- 2011, Al-Hiyasat 2006, strated that there was no statistical heterogeneity, as
combination of Hørsted et al. 1985
measured by the I2 statistic, between the results of
traumatic, carious or
mechanical exposures
the randomized and non-randomized studies at
or unclear cause of 12 months (v2 0.22, P = 0.64, I2 = 0%), but consid-
exposure erable at 2–3 years (v2 2.62, P = 0.11, I2 = 61%). In
Pulpotomy 1 Linsuwanont et al. 2017 the sensitivity analyses, the study whose data might
Less than 12-month 1 Hedge et al. 2017
be contaminated by teeth with immature apices (Cho
follow-up
Unacceptable drop our 3 Bjørndal et al. 2017,
et al. 2013) was removed, MTA out-performed cal-
rate Brizuela et al. 2017, cium hydroxide at 12 months (OR 2.34 95% CI;
Marques et al. 2015 1.05–5.23, P = 0.04) and 2–3 year (OR 2.65, 95%
Language- not in 1 Gora et al. 2008 CI; 1.40–5.04, P = 0.003).
English

MTA versus Biodentine as pulp capping material

receiving the intervention (thereby assuming that
those lost to follow-up were failures). Success rates for
DPC were pooled from the randomized trials and
other non-randomized comparative studies based on
the material used and follow-up at 6, 12, 36, and
60 months (Table 4). This analysis revealed that the
pooled success rates for DPC with calcium hydroxide,
MTA and Biodentine at 6 months were 74%, 91%
and 96% respectively. At 12-month follow-up, the
rates were 65% for calcium hydroxide, 86% for MTA
and 86% for Biodentine. At 2- to 3-year follow-up,
calcium hydroxide had a pooled success rate of 59%,
MTA was 84% and Biodentine was 86%. Finally, at
4- to 5-year review, the calcium hydroxide success
rate was 56% and it was 81% for MTA.
If the results of the study where it was not possible
to disaggregate data for teeth with immature apices
were removed from the meta-analysis, this did not
significantly alter the success rate (Cho et al. 2013),
where the success rate at 1 year slightly reduced to
A meta-analysis on the success of pulp capping using
MTA in comparison with Biodentine is shown in
Fig. 3, again demonstrating randomized and non-ran-
domized studies separately and combined. There is no
significant difference between the two materials at
any of the three time-points or between the results of
the randomized and the non-randomized studies at
the one time-point when both are available (1 year).
Discussion
There is currently no consensus on the most appro-
priate evidence-based approach to the management of
cariously exposed pulp (ESE 2019). The recommended
approach to the management of the deep caries lesion
is to use selective caries removal to avoid pulp expo-
sure (Schwendicke et al. 2016), but when exposure
occurs, a conservative approach is recommended.
Amongst the treatment options, DPC is the most con-
servative and simplest approach to maintain the

© 2020 International Endodontic Journal. Published by John Wiley & Sons Ltd International Endodontic Journal, 54, 556–571, 2021 561
 13652591, 2021, 4, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/iej.13449 by Nat Prov Indonesia, Wiley Online Library on [27/07/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
Direct pulp capping for cariously exposed pulps Cushley et al.

Table 2 Population/participants characteristics

Teeth Mean/Median
receiving Mean (age follow-up Type of Gender Pulpal Cause of Root
Studies intervention years) (months) Tooth (M : F) diagnosis exposure development

Awawdeh 68 32.5 18 5-I, 18-PM 23 : 35 RP Carious CA

et al. 2018 45-Mo
Bjørndal 27 NS 14.86 NS NS RP Carious CA
et al. 2010
Bogen et al. 53 16.6 47.28 51-Mo, 1- 15 : 22 RP Carious 15 OA, 38
2008 PM, 1-I CA
Barthel et al. 401 10–70 60&120 NS 60 : 63 RP Carious CA
2000

alıs
kan and
C 172 29.7 37.3 25-Ant;127- 85 : 67 RP Carious CA
G€uneri, Post
2017
Cho et al. 175 NS 13.7 123 Mo, 36 85 : 90 RP Carious NS
2013 PM, 16
Ant
Farsi et al. 30 10.5 6–24 Mo NS RP Carious 22 OA, 8CA
2006
Kundzina 70 30 18 Mo NS Normal Carious CA
et al. 2017 or RP
Kusumvalli 7 15–40 12 Mo/PM NS RP Carious CA
et al. 2019
Linu et al. 30 15–30 12&18 Mo 5 : 21 RP Carious CA
2017
Mente et al. 167 40.1 27 NS NS RP 106 carious, NS
2010 61
mechanical
Mente et al. 229 44 24–123 NS NS RP 176 carious, NS
2014 53
mechanical
Parinyaprom 59 10  2 18.9  12.9 NS NS Normal, Carious 27OA, 28CA
et al. 2018 RP,IRP
Suhag et al. 64 21.8  5.91 12 Mo 41 : 23 RP Carious CA
2019

Ant, Anterior Teeth, Post, Posterior teeth; C, Canine; CA, Closed apex; F, Female; I, Incisor; M, Male; Mo, Molar; NS, Not Specified;
OA, Open Apex; PM, Premolar; RP, Reversible Pulpitis.

vitality of pulp as it does not involve the removal of
pulp tissue compared with pulpotomy procedures.
This systematic review aimed to provide unbiased,
high-quality evidence on the outcomes of DPC for
teeth with deep caries and cariously exposed pulps.
The review adopted specific inclusion criteria to
address the clinical question of whether DPC of cari-
ously exposed pulp with a diagnosis of normal or
reversible pulpitis is clinically effective. The findings
highlighted that in general, the success rate for DPC
is high, particularly at early time points and that the
choice of capping material influenced the outcome
over longer-term follow-up. The outcome for pulp
capping using calcium hydroxide was comparable to
that of the hydraulic calcium silicate cements, MTA
and Biodentine at six-month follow-up, but at 12-
month and longer follow-up, MTA performed better
than calcium hydroxide in both the randomized and
non-randomized direct comparisons. MTA and Bio-
dentine had similar outcomes to each other in both
short and longer term follow-up. The overall success
reported for DPC with MTA is comparable to that
reported for other VPT techniques, including indirect
pulp capping (Maltz et al. 2012), partial pulpotomy
(Elmsmari et al. 2019) and complete pulpotomy
(Alqaderi et al. 2016).
The optimal pulpcapping material should be bio-
compatible, antimicrobial, have mechanical strength,
effectively seal the pulp wound and stimulate the pro-
duction of a hard tissue barrier and promote tissue
repair (Schwendicke et al. 2016). Many materials
have been used (or suggested for use) for DPC

562 International Endodontic Journal, 54, 556–571, 2021 © 2020 International Endodontic Journal. Published by John Wiley & Sons Ltd
 Table 3 Included studies characteristics

Rubber Final Level of

Author, year Study design Location Intervention Comparator dam Restoration Outcome assessment Funding evidence*

Awawdeh et al. 2018 Randomized controlled Jordan DPC DPC MTA* Yes 14 Amalgam Clinical & NS 1b
trial Sweden Biodent 53 Composite Radiographic
Bjørndal et al. 2010 Randomized controlled Denmark DPC CaOH NA Yes Composite Clinical & DASTI 1b
trial Radiographic
Bogen et al. 2008 Prospective/single arm USA DPC MTA** NA Yes Composite Clinical & NS 2b
Radiographic
Barthel et al. 2000 Retrospective Germany DPC CaOH NA Yes NS Clinical & NS 3b
Radiographic
C uneri,

alıs
kan and G€ Retrospective/ Turkey DPC MTA** DPC CaOH NS NS Clinical & No 3b
2017 comparative Radiographic
Cho et al. 2013 Retrospective/ South DPC MTA** DPC CaOH Yes NS Clinical and NS 3b
comparative Korea Radiographic
Farsi et al. 2006 Prospective/single arm Saudi DPC MTA** NA No NS Clinical & NS 4
Arabia Radiographic

© 2020 International Endodontic Journal. Published by John Wiley & Sons Ltd
Kundzina et al. 2017 Randomized controlled Norway DPC MTA** DPC CaOH Yes NS Clinical & NS 1b
trial Radiographic
Kusumvalli et al. 2019 Prospective single arm India DPC NA Yes Composite Clinical & NS 4
Biodent Radiographic
Linu et al. 2017 Retrospective / India DPC MTA** DPC NS NS Clinical & NS 3b
Comparative Biodent Radiographic
Mente et al. 2010 Retrospective / Germany DPC MTA** DPC CaOH Yes NS Clinical & NS 3b
Comparative Radiographic
Mente et al. 2014 Retrospective / Germany DPC MTA** DPC CaOH Yes NS Clinical & NS 3b
Comparative Radiographic
Parinyaprom et al. Randomized controlled Thailand DPC MTA** DPC NS NS Clinical & PMU 2b
2018 trial Biodent Radiographic
Suhag et al. 2019 Randomized controlled India DPC CaOH DPC MTA NS NS Clinical & NS 1b
trial Radiographic

Biodent, Biodentine; Ca (OH), Calcium hydroxide; DASTI, Danish Agency for Science Technology and Innovation; DPC, Direct pulp capping; MTA, Mineral Trioxide Aggregate; NA,
not applicable; NS, not specified; PMU, Pomeranian Medical University.
*Oxford Centre for Evidence-based Medicine.
*MTA (Angelus, Londrina, Brazil), **ProRoot MTA (Dentsply, Tulsa, OK, USA).

International Endodontic Journal, 54, 556–571, 2021

Cushley et al. Direct pulp capping for cariously exposed pulps

563
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Direct pulp capping for cariously exposed pulps Cushley et al.

(a)

(b)

(c)

Figure 2 Outcome of DPC of cariously exposed pulp with CaOH and MTA at: (A) 6-month, (B) 1 year and (C) 2–3 years.
There is no difference between MTA and CaOH at 6 months, but at one year and 2- to 3-year follow-up, MTA has better suc-
cess compared to CaOH. Subgroup analysis showed no significant effect of study design on the overall difference between the
groups. Risk of Bias Legend A: Random sequence generation; B: Allocation concealment; C: Blinding of participants; D: Blind-
ing of outcome assessment; E: incomplete outcome data; F: Selective reporting; G: other bias. Red: high, Green low and yellow
unclear risk of bias.

564 International Endodontic Journal, 54, 556–571, 2021 © 2020 International Endodontic Journal. Published by John Wiley & Sons Ltd
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Cushley et al. Direct pulp capping for cariously exposed pulps

(a)

(b)

(c)

Figure 3 Outcome of DPC in cariously exposed pulp with Biod (Biodentine) and MTA at: (A) 6 month, (B) 1 year and (C)
3 years. There is no difference in the outcome of the two materials at any follow-up period. Subgroup analysis for 1-year fol-
low-up (B) showed no significant effect of study design on the overall difference between the groups. Risk of Bias Legend A:
Random sequence generation; B: Allocation concealment; C: Blinding of participants; D: Blinding of outcome assessment; E:
Incomplete outcome data; F: Selective reporting; G: other bias. Red: high, Green: low and Yellow: unclear risk of bias.

including calcium hydroxide, adhesives and hydraulic
calcium silicate cements (da Rosa et al. 2018). The
search criteria adopted for this review were not based
on the material used, but only studies in which cal-
cium hydroxide, MTA and Biodentine had been used
satisfied the inclusion criteria.
In summary, the data gathered for this review sug-
gest that the success of calcium hydroxide reduces
with long-term follow-up, whilst that of MTA and
Biodentine remained reasonably stable. Although
MTA and Biodentine share common biological proper-
ties with calcium hydroxide, the structural stability
and sealing ability of calcium hydroxide have been
reported to be lower than that of calcium silicate
cements such as MTA (Kitasako et al. 2008, Okiji &
Yoshiba 2009, Parirokh et al. 2018). Microleakage
and bacteria contamination are known to influence
the long-term outcome of VPT and preservation of
pulp vitality in general (Ritter & Swift 2003, Zanini
et al 2016). It is likely, therefore, that in the long-
term, failures in DPC with calcium hydroxide are
related to factors other than the biological effect of
the material. In support of this argument, calcium
hydroxide has a long-term track record of clinical

© 2020 International Endodontic Journal. Published by John Wiley & Sons Ltd International Endodontic Journal, 54, 556–571, 2021 565
 13652591, 2021, 4, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/iej.13449 by Nat Prov Indonesia, Wiley Online Library on [27/07/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
Direct pulp capping for cariously exposed pulps Cushley et al.

Table 4 Summary of the success rate of direct pulp capping of all studies in four follow-up points. The success rate for direct
pulp capping with Ca(OH)2, MTA and Biodentine was shown at 6 months follow-up (A), 1 year (B), 2- 3yrs (C) and 4–5 year
(D)

Ca(OH)2 MTA Biodentine

(A) 6 Months Success Total Success Total Success Total Success

Farsi et al. 2006 --- -- 8 8 (100%) -- --

Kundzina et al. 2017 37 30 (82%) 33 31 (95%) --- ---
Parinyaprom et al. 2018 --- --- 19 19 (100%) 17 16 (94%)
Awawdeh et al. 2018 --- --- 6 6 (100%) 11 11 (100%)
Suhag et al. 2019 32 21 (66%) 32 25 (78%) --- ---
Total 69 51 (74%) 98 89 (91%) 28 27 (96.4%)

Ca(OH)2 MTA Biodentine

(B) 1 year Success Total Success Total Success Total Success

Farsi et al. 2006 --- --- 8 6 (75%) --- ---

Cho et al. 2013 105 78 (74%) 70 63 (90%) --- ---
Kusumvalli et al. 2019 --- --- --- --- 7 6 (86%)
Linu et al. 2017 --- --- 15 11 (73%) 15 12 (80%)
Kundzina et al. 2017 37 26 (70%) 33 28 (90%)
Parinyaprom et al. 2018 --- --- 19 18 (95%) 17 15 (88%)
Bjørndal et al. 2010 27 7(26%) --- --- --- ---
Awawdeh et al. 2018 --- --- 6 6 (100%) 11 10 (91%)
Suhag et al. 2019 32 20 (63%) 32 25 (78%) --- ---
Total 201 131 (65%) 183 157 (86%) 50 43 (86%)

Ca(OH)2 MTA Biodentine

(C) 2–3 Years Success Total Success Total Success Total Success

Barthel et al. 2000 54 20 (37%) --- --- --- ---

Bogen et al. 2008 --- --- 53 49 (93%) --- ---
Cho et al. 2013 105 56 (53%) 70 47 (67%) --- ---
Farsi et al. 2006 --- --- 8 6 (75%) --- ---
Mente et al. 2010 47 29 (62%) 59 47(80%) --- ---

alıs
kan and G€
C uneri, 2017 67 60 (89.5%) 85 79 (93) --- ---
Kundzina et al. 2017 37 19 (52%) 33 28 (85%) --- ---
Awawdeh et al. 2018 --- --- 6 6 (100%) 11 9 (82%)
Parinyaprom et al. 2018 --- --- 19 17 (85%) 17 15 (88%)
Total 310 184 (59%) 333 279 (84%) 28 2( 86%)

Ca(OH)2 MTA Biodentine

(D) 4–5 Years Success Total Success Total Success Total Success

Barthel et al. 2000 54 20 (37%) --- --- ---- -----

Mente et al. 2014 49 28(57%) 127 101 (80%) ---- ----

alıs
kan and G€
C uneri, 2017 75 52(69.3%) 97 76(78.3%) ---- ----
Total 178 100 (56.1%) 218 177 (81%) ---- -----

success as a DPC when used by experienced clinicians
and in traumatically exposed pulp with no or mini-
mal bacterial contamination (Baume & Holz 1981).
It is worth noting here that the direct pulp capping
reported in the included studies falls under type II
pulp capping as defined by the ESE position statement
(ESE 2019). In type II cases, the pulp exposure hap-
pens through a zone of bacterial contamination and
the underlying pulp tissue is likely inflamed. It has
been suggested in this case that an enhanced opera-
tive protocol including aseptic procedure, use of mag-
nification, disinfectant and application of a hydraulic
calcium silicate cement is recommended (ESE, 2019).
The findings also show comparable results for MTA
and Biodentine at long-term follow-up. MTA and Bio-
dentine share common biological, chemical and

566 International Endodontic Journal, 54, 556–571, 2021 © 2020 International Endodontic Journal. Published by John Wiley & Sons Ltd

physical properties, but Biodentine is claimed to be
easier to handle and quicker setting than MTA (Tora-
binejad et al. 2018). However, the available studies
investigating Biodentine are limited by a small sample
size compared with the studies of MTA with evidence
of publication bias, the results for this material should
therefore be interpreted with caution (Careddu &
Duncan 2018).
There has been much debate about how age of
patients influences the outcome of DPC (Dammaschke
et al. 2010, Lipski et al. 2018). Ageing generally neg-
atively influences the dentine-pulp complex with pro-
gressive degenerative changes taking place. A second
factor related to age, which may also influence the
outcome is the state of root maturity. Two of the
included studies categorized patients by age without
confirming the stage of root development. Mente et al.
(2010) included subjects below the age of 25 years
but found age to not affect the success of DPC. Cho
et al. (2013) grouped participants according to age
into those ≥ 40 and < 40 years and found age to
influence success. In this study, mean age for the
study participants was not provided; therefore, there
is uncertainty as to whether all of the teeth included
were mature. The sensitivity analysis, which is
reported here, however, showed that the removal of
this study did not influence the outcomes.
Another important factor to be considered when
assessing outcomes of DPC in cariously exposed pulp
is the depth of caries penetration. The ESE position
statement (ESE 2019) considered penetration depth at
two levels; deep caries in which caries reached the
inner quarter of dentine, but with a zone of hard or
firm dentine between caries and the pulp, which is
radiographically detectable when located on an inter-
proximal or occlusal surface. In this situation, there is
a risk of pulp exposure during operative treatment.
The second depth, extremely deep caries penetrates
the entire thickness of the dentine, radiographically
detectable when located on an interproximal or occlu-
sal surface and pulp exposure is unavoidable during
operative treatment. Within the current review, some
included studies did not define the depth of caries
penetration and of those which did, the definitions of
carious depth varied (Kundzina et al. 2017, Awawdeh
et al. 2018, Parinyaprom et al. 2018, Suhag et al.
2019 ) to such an extent that it was not possible to
state categorically if they met the ESE definition of
deep caries. Bogen et al. (2008) description of caries
penetration is likely to fit with the current definition
of extremely deep caries, yet he reported a very high
© 2020 International Endodontic Journal. Published by John Wiley & Sons Ltd
13652591, 2021, 4, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/iej.13449 by Nat Prov Indonesia, Wiley Online Library on [27/07/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
Cushley et al. Direct pulp capping for cariously exposed pulps
success rate for MTA direct pulp capping of 93% at 3-
year follow-up. Unquestionably, caries depth is an
important factor in determining pulp status and
although the focus of this review was the pulpal diag-
nosis, it must be accepted that this is based on subjec-
tive symptoms and ‘crude’ diagnostic tests. In the
future, it is hoped that caries depth will be more rou-
tinely reported in clinical studies in this area.
This review, although limited by the number and
quality of the included studies has important
strengths. Unlike previous systematic reviews, it aims
to answer a specific and clinically relevant question
using a practical clinical outcome measure. The data
included only deep carious teeth with cariously
exposed pulp and established pulpal diagnosis. The
outcome measure was defined to reflect routine clini-
cal practice in which dentists will first assess teeth for
DPC based on the symptoms and responses to clinical
tests and thereafter assess outcome based on clinical
and radiographic findings to suggest the absence of
pulpal and periapical disease as well as confirming
pulp vitality using sensibility tests. Previous studies
have used hard tissue bridge formation as an outcome
for DPC (Fransson et al. 2016), which is an ideal his-
tologically attained outcome measure after VPT, but
hard tissue bridge may not be visible in all successful
cases of VPT (Kunert et al. 2015) and may have lim-
ited clinical relevance. The review excluded studies
with a dropout rate greater than 20% as it is well
known that greater than 20% loss poses serious
threats to trial validity (Schulz & Grimes 2002).
Inclusion of trials with high dropout may subse-
quently impact on the outcomes of systematic reviews
(Strauss et al. 2019).
A robust risk of bias assessment of included stud-
ies was used for this review, which demonstrated
that many studies have low methodological quality,
and this needs to be taken into account when
interpreting the strength of the results of the
review. Furthermore, there was considerable clinical
heterogeneity across the included studies. At the
population level, they studied different age groups,
different tooth types and gender ratios. Studies were
principally carried out in University Dental Hospi-
tals, with a more limited number carried out in
General Practice settings. The included studies were
of low to moderate quality and many are com-
pounded with high risk of bias. The level of evi-
dence of all the included studies was assessed using
OCfE-b, which represents a hierarchy of the likely
best evidence. OCfE-b provides a feasible and explicit
International Endodontic Journal, 54, 556–571, 2021 567

Direct pulp capping for cariously exposed pulps Cushley et al.
approach to evidence synthesis for practising clini-
cians. The level of evidence is graded from 1 to 5
based on study quality, precision, consistency and
effect size. As seen in the results, the level of evi-
dence varied amongst the studies including level 1b
which indicate good quality randomized control tri-
als to level 4 designated for poor-quality observa-
tional studies.
Future studies should adopt designs that take these
issues into account and also address other issues,
including the adoption of specific inclusion criteria,
adequate sample size (based on the previous litera-
ture) and appropriate practicality-based study design
and length of follow-up.
The evidence in this review suggests that direct
pulp capping is generally a clinically effective proce-
dure for treating teeth with deep caries and pathologi-
cally exposed pulps if the pulpal diagnosis is reversible
pulpitis. There is no evidence to support a difference
in short-term success (up to 6 months) between cal-
cium hydroxide and calcium silicate cements, but
MTA and Biodentine were better than calcium
hydroxide in the long term. Critically, this evidence
comes from studies with evidence of high risk of bias
and low methodological quality. Future well designed
and adequately powered randomized trials are
required to determine whether these findings are cor-
rect in order to resolve ongoing uncertainties.
Conflict of interest
The authors have stated explicitly that there are no
conflicts of interest in connection with this article.
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Supporting Information
Additional Supporting Information may be found in
the online version of this article:
Table S1. Search methods
Table S2. Quality assessment of non randomized
studies
Table S3. Summary sensitivity analysis
Figure S1. Publication bias graphs
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