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© 2021 Journal of Pharmacy and Bioallied Sciences | Published by Wolters Kluwer - Medknow
This systematic review aims to compare the success rate of Endosequence
bioceramic root repair material (BCRRM), mineral trioxide aggregate (MTA),
and calcium hydroxide for apexification of necrotic immature permanent
teeth. Indexed Journals such as Google Scholar, PubMed, Scopus, Cochrane,
Research Gate, Wiley Online Library, and other related journals were hand
searched from inception till November 2020 and articles were selected for
review based on PRISMA guidelines. Of the 410 studies that were identified,
150 articles were selected after title/abstract reading. After full‑text reading
and based on inclusion and exclusion criteria, 9 studies were finalized for
systematic review. Clinical, radiographic success, and the time taken for
apical barrier formation were reviewed. All the three materials had almost
similar success rate in terms of clinical symptoms, but the time taken for
apical barrier formation and also single visit treatment makes MTA and
Endosequence BCRRM superior to calcium hydroxide. Studies comparing
EndoSequence Root Repair Material and MTA are very limited and need
further evaluation in the future.
Keywords: Apexification, bioceramic, calcium hydroxide, endosequence, mineral
trioxide aggregate, randomized controlled trials
Comparison of the Success Rate of Mineral Trioxide Aggregate,
Endosequence Bioceramic Root Repair Material, and Calcium
Hydroxide for Apexification of Immature Permanent Teeth: Systematic
Review and Meta‑Analysis
Izaz Shaik, Bhargavi Dasari, Rashmi Kolichala1
, Mina Doos2
, Fida Qadri3
, Jenefer Loveline Arokiyasamy4
,
Rahul Vinay Chandra Tiwari5
Access this article online
Quick Response Code:
Website: www.jpbsonline.org
DOI: 10.4103/jpbs.JPBS_810_20
Address for correspondence: Dr. Izaz Shaik,
Rutgers School of Dental Medicine, Newark, NJ, USA.
E‑mail: shaik.ajas@gmail.com
now. The gold standard treatment initially was calcium
hydroxide with camphorated monochlorophenol to
induce the formation of the apical barrier at the apex
was proposed by Kaiser in 1964. However, this material
required almost 5–20 months to form the hard‑tissue
Introduction
Traumatic injuries are very common in childhood and
toddlers and upper front teeth are more vulnerable
for fracture. The root apex closes only after 3 years of
eruption. The necrosed open apex might have some
residual vital pulp tissues and some residual apical
papilla cells in the periapical tissue.[1,2]
The stem cells
present in the apical papilla favor root development.
Apexification is the accepted nonsurgical treatment
of choice for the necrotic immature permanent teeth.
Several materials are available for apexification until
DMD Student, Rutgers
School of Dental Medicine,
Newark, NJ, USA, 1
DMD
Student, Sri Venkata Sai
Institute of Dental Sciences,
3
Dental Surgeon, Panineeya
Institute of Dental Sciences
and Research Centre,
Hyderabad, Telangana,
5
Department of OMFS,
Narsinhbhai Patel Dental
College and Hospital,
Sankalchand Patel University,
Visnagar, Gujarat, 4
Dental
Surgeon, Rajah Muthiah
Dental College and Hospital,
Annamalai University,
Chidambaram, Tamil Nadu,
India, 2
Dental Surgeon,
Faculty of Dentistry and Oral
Medicine, Pharos University,
Alexandria, Egypt
Submitted: 06‑Dec‑2020
Revised: 07-Dec-2020
Accepted: 08‑Dec‑2020
Published: 05-Jun-2021.
This is an open access article distributed under the terms of the Creative Commons
Attribution‑NonCommercial‑ShareAlike 4.0 License, which allows others to remix, tweak,
and build upon the work non‑commercially, as long as the author is credited and the new
creations are licensed under the identical terms.
For reprints contact: WKHLRPMedknow_reprints@wolterskluwer.com
How to cite this article: Shaik I, Dasari B, Kolichala R, Doos M, Qadri F,
Arokiyasamy JL, et al. Comparison of the success rate of mineral trioxide
aggregate, endosequence bioceramic root repair material, and calcium
hydroxide for apexification of immature permanent teeth: Systematic
review and meta-analysis. J Pharm Bioall Sci 2021;13:S43-7.
Abstract
Review Article
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S44 Journal of Pharmacy and Bioallied Sciences  ¦  Volume 13  ¦  Supplement 1  ¦  June 2021
Shaik, et al.: Apexification of immature permanent teeth: Systematic review and meta analysis
barrier.[3]
Mineral trioxide aggregate (MTA) is used as
reparative material for perforations and also used in
pulp capping and pulpotomy procedures, apical barrier
for open apex, and retrograde filling.[4]
Several clinical
studies of role of MAT in apexification is present in
literature.[5,6]
MTA is a mixture of Portland cement and
bismuth oxide, dicalcium silicate, tricalcium silicate,
tricalcium aluminate, and tetracalcium aluminoferrite,
as well as other mineral oxides.[7]
The pH of 12.5 after
setting is almost the same as calcium hydroxide.[7]
MTA
is the first material that had allowed overgrowth of
cementum and promotes regeneration of periodontal
tissues.[8]
Nevertheless, MTA had some disadvantages like
discoloration of the tooth and it weakened dentine walls
like calcium hydroxide.[9]
Recently, newer bioceramic
materials such as calcium‑enriched cement, Biodentine,
and EndoSequence Root Repair Material (ERRM) have
been marketed for various other endodontic procedures.[10]
ERRM contains calcium silicates, tantalum oxide, calcium
phosphate monobasic, and little amount of filler agents.
The nanosphere particles present in the cement pass
through the dentin tubules and react with moisture present
in dentin. ERRM has a bioactive nature which simulates
tissue fluid and results in the precipitation of apatite
crystals.[11]
This systematic review is done to compare
the effectiveness of MTA and Endosequence bioceramic
root repair material (BCRRM) and calcium hydroxide in
clinical success of apexification of immature permanent
teeth, thus solving the problem for a clinician in choosing
the material for apexification is the main objective of the
present study.
Materials and Methods
PICO: Population, Intervention, Comparison, Outcome
is described in Table 1.
Search module for identification of studies
A detailed search of all databases were done for doing
this systematic review. The computer database list for
reviewing the article is listed in Table 2.
Strategy of publication research
An electronic search was performed with keywords
and filter in database as listed in Table  2. Comparative
studies of apexification of necrotic immature permanent
teeth that met the inclusion criteria were evaluated. The
reference list of relevant articles was also searched and
evaluated.
Inclusion criteria and exclusion criteria for the review
are listed in Table 3.
Data extraction and characteristics of the study
for review
The following information/data were extracted from
shortlisted studies: author’s name, year of publication,
Table 3: Inclusion and exclusion criteria
Inclusion criteria Exclusion criteria
Conducted clinical trials on patients with permanent immature
teeth for which apexification was indicated
Review articles
Randomized controlled trials, prospective and retrospective
studies, and case series
In vitro studies
Compared calcium hydroxide versus MTA versus endosequence Nonhuman studies, letters, comments
Reported quantitative clinical or radiographic outcomes Editorials, case reports, proceedings, and personal communications
were excluded
MTA: Mineral trioxide aggregate
Table 1: PICO question
P patient, population, or problem Immature necrotic permanent teeth
I intervention, prognostic factor, or exposure Biomaterials for apexification
C comparison or intervention (if appropriate) Calcium hydroxide, mineral trioxide aggregate, endosequence
O outcome you would like to measure or achieve Clinical success with no clinical signs and symptoms
radiographic apical closure (evaluating root length and thickness)
Table 2: Search strategy
Electronic
databases
Google Scholar, PubMed, Scopus, Cochrane, Research Gate, Wiley online library, and other hand searched journals:
Journal of endodontics, international endodontic journal, journal of conservative dentistry
Keywords Apexification, mineral trioxide aggregate, calcium hydroxide, bioceramic, endosequence, randomized controlled trials
Filters English language, humans, from source till November 2020
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S45
Journal of Pharmacy and Bioallied Sciences  ¦  Volume 13  ¦  Supplement 1  ¦  June 2021
Shaik, et al.: Apexification of immature permanent teeth: Systematic review and meta analysis
design of the study, number of teeth studied, age and
sex of the participants, clinical success and radiographic
success, time taken for apical barrier formation, and
follow‑up details evaluated.
Study selection
Of the 410 studies that were identified, 150 articles
were selected after title/abstract reading. After full‑text
reading and based on inclusion and exclusion criteria, 9
studies were finalized for systematic review. A flowchart
for selecting the articles for review was generated with
PRISMA guidelines listed in Figure 1.
Study characteristics
El Meligy and Avery[12]
aimed to compare the clinical
and radiographic success by conducting a study on 15
children with minimum 2 necrotic immature permanent
teeth. Apexification was done after root canal treatment
protocol with calcium hydroxide or MTA. The evaluation
was carried out every 3, 6, and 12 months. Only two teeth
among 15 teeth that were treated with calcium hydroxide
showed clinical symptoms such as tenderness on
percussion and persistent periradicular inflammation. None
of the teeth that were treated with MTA showed failure
on every 3‑, 6‑, and 12‑month follow‑up visit. Pradhan
et  al.[13]
conducted this study to compare the efficacy
and the time taken for apical biologic calcific barrier
formation and resolution of periapical radiolucencies on
20 teeth with unformed apices. Teeth were stratified based
on radiolucency in the periapical region. After routine
root canal treatment, Group I was packed with MTA
and obturated with gutta percha. In Group II, calcium
hydroxide dressing was done till the apical stop was
achieved and then obturated. The result showed that it
took 3 ± 2.9 months for apical barrier formation in MTA
groups and 7 ± 2.5 months in calcium hydroxide groups.
There was no significant difference in healing time of
periapical radiolucencies. Simon et  al.[14]
conducted a
prospective study (randomized) from June 2001 to June
2005 on 57 immature permanent teeth on 50 patients.
The same operator treated all teeth in one appointment.
The operator placed gray MTA in cases 1–11 and white
MTA in cases 11–57. The remaining part of the canal was
obturated with warm vertical compaction of gutta percha.
Two examiners assessed the pretreatment, posttreatment,
and review radiographs using magnifiers taken every 6
months, 12 months, and every year thereafter. Eighty‑one
percent of cases showed a decrease in size of the
periapical lesion. Apical foramen closure was 88%. Bonte
et al.[16]
conducted a randomized clinical trial on children
with necrotic permanent teeth with calcium hydroxide or
MTA apexification and evaluated after 6 and 12 months.
Fifty percent of the teeth treated with calcium hydroxide
group showed mineralized barrier and 82% in the MTA
apexification. However, four teeth treated with calcium
hydroxide showed radicular fractures and 82% in the MTA
group. Lee et al.[17]
conducted apexification study on 40
necrotic immature open apex incisors and evenly divided
them into diffrent groups (calcium hydroxide and MTA
with hand and ultrasonic filing). Two conclusions derived,
that root length elongation was better in teeth treated with
calcium hydroxide and short time need for apical barrier
in MTA apexification with ultrasonic filing. A comparative
study by Damle et  al.[18]
compared and evaluated the
apexification potential of calcium hydroxide and MTA in
22 traumatized young permanent anterior teeth among the
age group of 10–11 years, and the study revealed MTA
showing superior clinical outcome compared to calcium
hydroxide with MTA showing 90.9% success and calcium
Figure 1: PRISMA guidelines for study selection
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S46 Journal of Pharmacy and Bioallied Sciences  ¦  Volume 13  ¦  Supplement 1  ¦  June 2021
Shaik, et al.: Apexification of immature permanent teeth: Systematic review and meta analysis
hydroxide showed only 81.8% success rate. Sarnowski[19]
had done a thesis on open apex treated with bioceramic
apical barrier and studied its success and survival rates at
Virginia Commonwealth University in 2019. Patient record
taken from resident cases completed at the university
from January 1, 2010 to May 31, 2018. A total of 119
teeth were identified that were treated for open apex with
BCRRM. Only 36 teeth were under follow‑up in which
72% were considered healed and 2% were healing which
shows bioceramic apical had showed a good clinical
outcome. Study by Barakat and Fethi.[20]
The study was
composed of sixty teeth from 54 children with age ranged
from 7 to 10 years. Children were divided in to two equal
groups: 1‑Group A: teeth were received apexification with
MTA 2‑Group B: teeth were received apexification with
bioceramic root canal sealer. All patients were followed
clinically and radiographically immediate postoperatively,
3 and 6 months [Table 4].
Results
The success rate in both bioceramic and MTA was
93.3% and 90%, respectively, with no statistically
significant difference. Conclusions: both MTA and
bioceramic sealer show good results.
Discussion
The purpose of this systematic review was to determine
whether Endosequence BCRRM, MTA or calcium
hydroxide provides better clinical and radiologic
outcomes for the apexification of immature permanent
teeth. These three materials have their unique
advantages and drawbacks and also there is no literature
evidence comparing these three materials. There are
few systematic reviews and meta‑analysis comparing
calcium hydroxide and MTA only. Three systematic
reviews and meta‑analysis by Lin et al.,[21]
Chala et al.[22]
and Nicoloso et al.,[23]
compared calcium hydroxide and
MTA for apexification of immature permanent teeth,
studies reviewed and concluded that MTA showed better
healing in terms of clinical and radiographic success,
and the apical barrier was formed within a short period
of time compared to calcium hydroxide. Although MTA
proved to be a promising material for apexification, it
carries some disadvantages such as discoloration and
weakening of dentine walls.[9]
Duraivel[24]
in   2014,
described a series of cases where apexification was
performed in single visit in three different patients using
ERRM, MTA, and Biodentin. All the patients were
recalled after 1 month for follow‑up and it proved that
ERRM can be used as an alternative to MTA. Although
ERRM is considered as a substitute for MTA, only
Table 4: Studies investigated for systematic review
Study (years) Study type Sample
size
Intervention Age
(years)
Clinical
success (%)
Radiographic
success (%)
Time required for apical
barrier formation
El Meligy and
Avery[12]
(2006)
RCT 15 MTA NR 100 100 NR (follow-up - 3, 6, and
9 months)
RCT 15 Calcium hydroxide 6-12 87 87 NR (follow-up - 3, 6, and
9 months)
Pradhan et al.[13]
(2006)
Clinical
comparative study
10 MTA NR 100 NR 3±2.9 months
10 Calcium hydroxide NR 100 NR 7±2.5 months
Simon et al.[14]
(2007)
Prospective study 57 MTA 18 81 88 Follow-up - 12 months
Neveu et al.[15]
(2011)
RCT 15
15
MTA
Calcium hydroxide
6-18 NR NRV Follow-up - 3, 6, and 12
months
Bonte et al.[16]
(2015)
In vivo clinical
trial
17
16
MTA
Calcium hydroxide
10.2
10.9
83.4
75
76.5
50
NR
Lee et al.[17]
(2015)
RCT 40 MTA and CaOH
with ultrasonic and
hand filing
6.5-10 100 100 5.4±1.1 weeks
Damle et al.[18]
(2016)
RCT 11
11
MTA
Calcium hydroxide
10±1.41
10.8±1.32
100
93.3
90.9
81.8
4.9
5.3
Sarnowski[19]
(2019)
Published
dissertation
36 Bioceramic (proroot
MTA, endosequence
root repair material)
17 92 92 Follow-up up to 2 years
Barakat and
Fethi[20]
(2020)
In vivo clinical
trial
30
30
MTA
Bioceramic root
canal sealer
9±1.2
9.5±1.08
100
100
90
93.3
3 months
MTA: Mineral trioxide aggregate, NR: Not reported, RCT: Randomized clinical trials
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S47
Journal of Pharmacy and Bioallied Sciences  ¦  Volume 13  ¦  Supplement 1  ¦  June 2021
Shaik, et al.: Apexification of immature permanent teeth: Systematic review and meta analysis
very few articles compared Endosequence and MTA
for apexification of nonvital immature permanent teeth.
Further clinical trials need to be conducted to compare
it with other apexification materials. Few stidues were
baised due to lack of proper random sequencing,
improper employed blinding and no long term follow
up. Therefore, more studies are required to compare all
apexification materials with an appropriate allocation
concealment, randomization technique, and blinding.
Conclusion
Based on the above studies evaluated, all the three
materials had almost similar clinical success rates,
radiographic success rates, and apical barrier formation
rates. However, MTA and Endosequence BCRRM were
associated with a significantly shorter time to achieve
apical barrier formation than the calcium hydroxide.
Although MTA and ERRM showed good results, there are
only limited studies to evaluate MTA and ERRM. Hence,
more comparative studies are required to prove the best
material for apexification of immature permanent teeth.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
References
1.	 Chueh LH, Ho YC, Kuo TC, Lai WH, Chen YH, Chiang CP.
Regenerative endodontic treatment for necrotic immature
permanent teeth. J Endod 2009;35:160‑4.
2.	 Huang  GT, Sonoyama  W, Liu  Y, Liu  H, Wang  S, Shi  S. The
hidden treasure in apical papilla: The potential role in pulp/dentin
regeneration and bioroot engineering J Endod 2008;34:645‑51.
3.	 Sheehy  EC, Roberts  GJ. Use of calcium hydroxide for apical
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teeth: A review. Br Dent J 1997;183:241‑6.
4.	 Anthonappa  RP, King  NM, Martens  LC. Is there sufficient
evidence to support the long‑term efficacy of mineral trioxide
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Endod J 2013;46:198‑204.
5.	 Damle SG, Bhattal H, Loomba A. Apexification of anterior teeth:
A comparative evaluation of mineral trioxide aggregate and
calcium hydroxide paste. J Clin Pediatr Dent 2012;36:263‑8.
6.	 Park M, Ahn BD. Immature permanent teeth with apical
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treatment using calcium hydroxide and MTA: A  report of two
cases. Pediatr Dent 2014;36:107‑10.
7.	 Sarkar NK, Caicedo R, Ritwik P, Moiseyeva R, Kawashima I.
Physicochemical basis of the biologic properties of mineral
trioxide aggregate. J Endod 2005;31:97‑100.
8.	 Parirokh  M, Torabinejad  M. Mineral trioxide aggregate:
A comprehensive literature reviewe Part III: Clinical applications,
drawbacks, and mechanism of action. J Endod 2010;36:400‑13.
9.	 Krastl G, Allgayer N, Lenherr P, Filippi A, Taneja P, Weiger R.
Tooth discoloration induced by endodontic materials: A literature
review. Dent Traumatol 2013;29:2‑7.
10.	 Utneja S, Nawal RR, Talwar S, Verma M. Current perspectives
of bio‑ceramic technology in endodontics: Calcium enriched
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applications. Restor Dent Endod 2015;40:1‑13.
11.	 Damas BA, Wheater MA, Bringas JS, Hoen MM. Cytotoxicity
comparison of mineral trioxide aggregates and endoSequence
bioceramic root repair materials. J Endod 2011;37:372‑5.
12.	 El Meligy  OA, Avery  DR. Comparison of apexification with
mineral trioxide aggregate and calcium hydroxide. J Pediatr Dent
2006;28:248‑53.
13.	 Pradhan  DP, Chawla  HS, Gauba  K, Goyal  A. Comparative
evaluation of endodontic management of teeth with unformed
apices with mineral trioxide aggregate and calcium hydroxide.
J Dent Child (Chic) 2006;73:79‑85.
14.	 Simon S, Rilliard F, Berdal A, Machtou P. The use of mineral
trioxide aggregate in one‑visit apexification treatment:
A prospective study. Int Endod J 2007;40:186‑97.
15.	 Neveu B, Bonte E, Baune B, Serreau S, Aissal F, Quinquis L,
et al. Mineral trioxyde aggregate versus calcium hydroxide in
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randomized controlled trial. Trials 2011;12:174.
16.	 Bonte E, Beslot A, Boukpessi T, Lasfargues JJ. MTA versus
Ca(OH)2
in apexification of non‑vital immature permanent
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17.	 Lee LW, Hsieh SC, Lin YH, Huang CF, Hsiao SH, Hung WC.
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Assoc 2015;114:139‑46.
18.	 Damle  SG, Bhattal  H, Damle  D, Dhindsa  A, Loomba  A,
Singla S. Clinical and radiographic assessment of mineral
trioxide aggregate and calcium hydroxide as apexification agents
in traumatized young permanent anterior teeth: A  comparative
study. Dent Res J 2016;13:284‑91.
19.	 Sarnowski A. Management of Open Apex Using a Bioceramic
apical Barrier‑its Success and Survival Rates at Virginia
Commonwealth University. VCU: Virginia Common Wealth
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20.	Barakat IF, Fethi A. Clinical and radiographical evaluation
of bioceramic root canal sealer and MTA in apexification of
immature permanent teeth. Egypt Dent J 2020;66:2057‑63.
21.	 Lin JC, Xuan Lu JX, Zeng Q, Zhao W, Li WQ, Ling JQ.
Comparison of mineral trioxide aggregate and calcium hydroxide
for apexification of immature permanent teeth: A  systematic
review and meta‑analysis. J Formos Med Assoc 2016;115:523‑30.
22.	 Chala  S, Abouqal  R, Rida  S. Apexification of immature teeth
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Radiol Endod 2011;112:e36‑42.
23.	 Nicoloso GF, Pötter IG, Rocha RO, Montagner F, Casagrande L.
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24.	 Duraivel D. Management of non vital teeth with open apex using
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253rd publication jpbs- 7th name

  • 1. S43 © 2021 Journal of Pharmacy and Bioallied Sciences | Published by Wolters Kluwer - Medknow This systematic review aims to compare the success rate of Endosequence bioceramic root repair material (BCRRM), mineral trioxide aggregate (MTA), and calcium hydroxide for apexification of necrotic immature permanent teeth. Indexed Journals such as Google Scholar, PubMed, Scopus, Cochrane, Research Gate, Wiley Online Library, and other related journals were hand searched from inception till November 2020 and articles were selected for review based on PRISMA guidelines. Of the 410 studies that were identified, 150 articles were selected after title/abstract reading. After full‑text reading and based on inclusion and exclusion criteria, 9 studies were finalized for systematic review. Clinical, radiographic success, and the time taken for apical barrier formation were reviewed. All the three materials had almost similar success rate in terms of clinical symptoms, but the time taken for apical barrier formation and also single visit treatment makes MTA and Endosequence BCRRM superior to calcium hydroxide. Studies comparing EndoSequence Root Repair Material and MTA are very limited and need further evaluation in the future. Keywords: Apexification, bioceramic, calcium hydroxide, endosequence, mineral trioxide aggregate, randomized controlled trials Comparison of the Success Rate of Mineral Trioxide Aggregate, Endosequence Bioceramic Root Repair Material, and Calcium Hydroxide for Apexification of Immature Permanent Teeth: Systematic Review and Meta‑Analysis Izaz Shaik, Bhargavi Dasari, Rashmi Kolichala1 , Mina Doos2 , Fida Qadri3 , Jenefer Loveline Arokiyasamy4 , Rahul Vinay Chandra Tiwari5 Access this article online Quick Response Code: Website: www.jpbsonline.org DOI: 10.4103/jpbs.JPBS_810_20 Address for correspondence: Dr. Izaz Shaik, Rutgers School of Dental Medicine, Newark, NJ, USA. E‑mail: shaik.ajas@gmail.com now. The gold standard treatment initially was calcium hydroxide with camphorated monochlorophenol to induce the formation of the apical barrier at the apex was proposed by Kaiser in 1964. However, this material required almost 5–20 months to form the hard‑tissue Introduction Traumatic injuries are very common in childhood and toddlers and upper front teeth are more vulnerable for fracture. The root apex closes only after 3 years of eruption. The necrosed open apex might have some residual vital pulp tissues and some residual apical papilla cells in the periapical tissue.[1,2] The stem cells present in the apical papilla favor root development. Apexification is the accepted nonsurgical treatment of choice for the necrotic immature permanent teeth. Several materials are available for apexification until DMD Student, Rutgers School of Dental Medicine, Newark, NJ, USA, 1 DMD Student, Sri Venkata Sai Institute of Dental Sciences, 3 Dental Surgeon, Panineeya Institute of Dental Sciences and Research Centre, Hyderabad, Telangana, 5 Department of OMFS, Narsinhbhai Patel Dental College and Hospital, Sankalchand Patel University, Visnagar, Gujarat, 4 Dental Surgeon, Rajah Muthiah Dental College and Hospital, Annamalai University, Chidambaram, Tamil Nadu, India, 2 Dental Surgeon, Faculty of Dentistry and Oral Medicine, Pharos University, Alexandria, Egypt Submitted: 06‑Dec‑2020 Revised: 07-Dec-2020 Accepted: 08‑Dec‑2020 Published: 05-Jun-2021. This is an open access article distributed under the terms of the Creative Commons Attribution‑NonCommercial‑ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non‑commercially, as long as the author is credited and the new creations are licensed under the identical terms. For reprints contact: WKHLRPMedknow_reprints@wolterskluwer.com How to cite this article: Shaik I, Dasari B, Kolichala R, Doos M, Qadri F, Arokiyasamy JL, et al. Comparison of the success rate of mineral trioxide aggregate, endosequence bioceramic root repair material, and calcium hydroxide for apexification of immature permanent teeth: Systematic review and meta-analysis. J Pharm Bioall Sci 2021;13:S43-7. Abstract Review Article [Downloaded free from http://www.jpbsonline.org on Sunday, June 6, 2021, IP: 175.101.146.64]
  • 2. S44 Journal of Pharmacy and Bioallied Sciences  ¦  Volume 13  ¦  Supplement 1  ¦  June 2021 Shaik, et al.: Apexification of immature permanent teeth: Systematic review and meta analysis barrier.[3] Mineral trioxide aggregate (MTA) is used as reparative material for perforations and also used in pulp capping and pulpotomy procedures, apical barrier for open apex, and retrograde filling.[4] Several clinical studies of role of MAT in apexification is present in literature.[5,6] MTA is a mixture of Portland cement and bismuth oxide, dicalcium silicate, tricalcium silicate, tricalcium aluminate, and tetracalcium aluminoferrite, as well as other mineral oxides.[7] The pH of 12.5 after setting is almost the same as calcium hydroxide.[7] MTA is the first material that had allowed overgrowth of cementum and promotes regeneration of periodontal tissues.[8] Nevertheless, MTA had some disadvantages like discoloration of the tooth and it weakened dentine walls like calcium hydroxide.[9] Recently, newer bioceramic materials such as calcium‑enriched cement, Biodentine, and EndoSequence Root Repair Material (ERRM) have been marketed for various other endodontic procedures.[10] ERRM contains calcium silicates, tantalum oxide, calcium phosphate monobasic, and little amount of filler agents. The nanosphere particles present in the cement pass through the dentin tubules and react with moisture present in dentin. ERRM has a bioactive nature which simulates tissue fluid and results in the precipitation of apatite crystals.[11] This systematic review is done to compare the effectiveness of MTA and Endosequence bioceramic root repair material (BCRRM) and calcium hydroxide in clinical success of apexification of immature permanent teeth, thus solving the problem for a clinician in choosing the material for apexification is the main objective of the present study. Materials and Methods PICO: Population, Intervention, Comparison, Outcome is described in Table 1. Search module for identification of studies A detailed search of all databases were done for doing this systematic review. The computer database list for reviewing the article is listed in Table 2. Strategy of publication research An electronic search was performed with keywords and filter in database as listed in Table  2. Comparative studies of apexification of necrotic immature permanent teeth that met the inclusion criteria were evaluated. The reference list of relevant articles was also searched and evaluated. Inclusion criteria and exclusion criteria for the review are listed in Table 3. Data extraction and characteristics of the study for review The following information/data were extracted from shortlisted studies: author’s name, year of publication, Table 3: Inclusion and exclusion criteria Inclusion criteria Exclusion criteria Conducted clinical trials on patients with permanent immature teeth for which apexification was indicated Review articles Randomized controlled trials, prospective and retrospective studies, and case series In vitro studies Compared calcium hydroxide versus MTA versus endosequence Nonhuman studies, letters, comments Reported quantitative clinical or radiographic outcomes Editorials, case reports, proceedings, and personal communications were excluded MTA: Mineral trioxide aggregate Table 1: PICO question P patient, population, or problem Immature necrotic permanent teeth I intervention, prognostic factor, or exposure Biomaterials for apexification C comparison or intervention (if appropriate) Calcium hydroxide, mineral trioxide aggregate, endosequence O outcome you would like to measure or achieve Clinical success with no clinical signs and symptoms radiographic apical closure (evaluating root length and thickness) Table 2: Search strategy Electronic databases Google Scholar, PubMed, Scopus, Cochrane, Research Gate, Wiley online library, and other hand searched journals: Journal of endodontics, international endodontic journal, journal of conservative dentistry Keywords Apexification, mineral trioxide aggregate, calcium hydroxide, bioceramic, endosequence, randomized controlled trials Filters English language, humans, from source till November 2020 [Downloaded free from http://www.jpbsonline.org on Sunday, June 6, 2021, IP: 175.101.146.64]
  • 3. S45 Journal of Pharmacy and Bioallied Sciences  ¦  Volume 13  ¦  Supplement 1  ¦  June 2021 Shaik, et al.: Apexification of immature permanent teeth: Systematic review and meta analysis design of the study, number of teeth studied, age and sex of the participants, clinical success and radiographic success, time taken for apical barrier formation, and follow‑up details evaluated. Study selection Of the 410 studies that were identified, 150 articles were selected after title/abstract reading. After full‑text reading and based on inclusion and exclusion criteria, 9 studies were finalized for systematic review. A flowchart for selecting the articles for review was generated with PRISMA guidelines listed in Figure 1. Study characteristics El Meligy and Avery[12] aimed to compare the clinical and radiographic success by conducting a study on 15 children with minimum 2 necrotic immature permanent teeth. Apexification was done after root canal treatment protocol with calcium hydroxide or MTA. The evaluation was carried out every 3, 6, and 12 months. Only two teeth among 15 teeth that were treated with calcium hydroxide showed clinical symptoms such as tenderness on percussion and persistent periradicular inflammation. None of the teeth that were treated with MTA showed failure on every 3‑, 6‑, and 12‑month follow‑up visit. Pradhan et  al.[13] conducted this study to compare the efficacy and the time taken for apical biologic calcific barrier formation and resolution of periapical radiolucencies on 20 teeth with unformed apices. Teeth were stratified based on radiolucency in the periapical region. After routine root canal treatment, Group I was packed with MTA and obturated with gutta percha. In Group II, calcium hydroxide dressing was done till the apical stop was achieved and then obturated. The result showed that it took 3 ± 2.9 months for apical barrier formation in MTA groups and 7 ± 2.5 months in calcium hydroxide groups. There was no significant difference in healing time of periapical radiolucencies. Simon et  al.[14] conducted a prospective study (randomized) from June 2001 to June 2005 on 57 immature permanent teeth on 50 patients. The same operator treated all teeth in one appointment. The operator placed gray MTA in cases 1–11 and white MTA in cases 11–57. The remaining part of the canal was obturated with warm vertical compaction of gutta percha. Two examiners assessed the pretreatment, posttreatment, and review radiographs using magnifiers taken every 6 months, 12 months, and every year thereafter. Eighty‑one percent of cases showed a decrease in size of the periapical lesion. Apical foramen closure was 88%. Bonte et al.[16] conducted a randomized clinical trial on children with necrotic permanent teeth with calcium hydroxide or MTA apexification and evaluated after 6 and 12 months. Fifty percent of the teeth treated with calcium hydroxide group showed mineralized barrier and 82% in the MTA apexification. However, four teeth treated with calcium hydroxide showed radicular fractures and 82% in the MTA group. Lee et al.[17] conducted apexification study on 40 necrotic immature open apex incisors and evenly divided them into diffrent groups (calcium hydroxide and MTA with hand and ultrasonic filing). Two conclusions derived, that root length elongation was better in teeth treated with calcium hydroxide and short time need for apical barrier in MTA apexification with ultrasonic filing. A comparative study by Damle et  al.[18] compared and evaluated the apexification potential of calcium hydroxide and MTA in 22 traumatized young permanent anterior teeth among the age group of 10–11 years, and the study revealed MTA showing superior clinical outcome compared to calcium hydroxide with MTA showing 90.9% success and calcium Figure 1: PRISMA guidelines for study selection [Downloaded free from http://www.jpbsonline.org on Sunday, June 6, 2021, IP: 175.101.146.64]
  • 4. S46 Journal of Pharmacy and Bioallied Sciences  ¦  Volume 13  ¦  Supplement 1  ¦  June 2021 Shaik, et al.: Apexification of immature permanent teeth: Systematic review and meta analysis hydroxide showed only 81.8% success rate. Sarnowski[19] had done a thesis on open apex treated with bioceramic apical barrier and studied its success and survival rates at Virginia Commonwealth University in 2019. Patient record taken from resident cases completed at the university from January 1, 2010 to May 31, 2018. A total of 119 teeth were identified that were treated for open apex with BCRRM. Only 36 teeth were under follow‑up in which 72% were considered healed and 2% were healing which shows bioceramic apical had showed a good clinical outcome. Study by Barakat and Fethi.[20] The study was composed of sixty teeth from 54 children with age ranged from 7 to 10 years. Children were divided in to two equal groups: 1‑Group A: teeth were received apexification with MTA 2‑Group B: teeth were received apexification with bioceramic root canal sealer. All patients were followed clinically and radiographically immediate postoperatively, 3 and 6 months [Table 4]. Results The success rate in both bioceramic and MTA was 93.3% and 90%, respectively, with no statistically significant difference. Conclusions: both MTA and bioceramic sealer show good results. Discussion The purpose of this systematic review was to determine whether Endosequence BCRRM, MTA or calcium hydroxide provides better clinical and radiologic outcomes for the apexification of immature permanent teeth. These three materials have their unique advantages and drawbacks and also there is no literature evidence comparing these three materials. There are few systematic reviews and meta‑analysis comparing calcium hydroxide and MTA only. Three systematic reviews and meta‑analysis by Lin et al.,[21] Chala et al.[22] and Nicoloso et al.,[23] compared calcium hydroxide and MTA for apexification of immature permanent teeth, studies reviewed and concluded that MTA showed better healing in terms of clinical and radiographic success, and the apical barrier was formed within a short period of time compared to calcium hydroxide. Although MTA proved to be a promising material for apexification, it carries some disadvantages such as discoloration and weakening of dentine walls.[9] Duraivel[24] in   2014, described a series of cases where apexification was performed in single visit in three different patients using ERRM, MTA, and Biodentin. All the patients were recalled after 1 month for follow‑up and it proved that ERRM can be used as an alternative to MTA. Although ERRM is considered as a substitute for MTA, only Table 4: Studies investigated for systematic review Study (years) Study type Sample size Intervention Age (years) Clinical success (%) Radiographic success (%) Time required for apical barrier formation El Meligy and Avery[12] (2006) RCT 15 MTA NR 100 100 NR (follow-up - 3, 6, and 9 months) RCT 15 Calcium hydroxide 6-12 87 87 NR (follow-up - 3, 6, and 9 months) Pradhan et al.[13] (2006) Clinical comparative study 10 MTA NR 100 NR 3±2.9 months 10 Calcium hydroxide NR 100 NR 7±2.5 months Simon et al.[14] (2007) Prospective study 57 MTA 18 81 88 Follow-up - 12 months Neveu et al.[15] (2011) RCT 15 15 MTA Calcium hydroxide 6-18 NR NRV Follow-up - 3, 6, and 12 months Bonte et al.[16] (2015) In vivo clinical trial 17 16 MTA Calcium hydroxide 10.2 10.9 83.4 75 76.5 50 NR Lee et al.[17] (2015) RCT 40 MTA and CaOH with ultrasonic and hand filing 6.5-10 100 100 5.4±1.1 weeks Damle et al.[18] (2016) RCT 11 11 MTA Calcium hydroxide 10±1.41 10.8±1.32 100 93.3 90.9 81.8 4.9 5.3 Sarnowski[19] (2019) Published dissertation 36 Bioceramic (proroot MTA, endosequence root repair material) 17 92 92 Follow-up up to 2 years Barakat and Fethi[20] (2020) In vivo clinical trial 30 30 MTA Bioceramic root canal sealer 9±1.2 9.5±1.08 100 100 90 93.3 3 months MTA: Mineral trioxide aggregate, NR: Not reported, RCT: Randomized clinical trials [Downloaded free from http://www.jpbsonline.org on Sunday, June 6, 2021, IP: 175.101.146.64]
  • 5. S47 Journal of Pharmacy and Bioallied Sciences  ¦  Volume 13  ¦  Supplement 1  ¦  June 2021 Shaik, et al.: Apexification of immature permanent teeth: Systematic review and meta analysis very few articles compared Endosequence and MTA for apexification of nonvital immature permanent teeth. Further clinical trials need to be conducted to compare it with other apexification materials. Few stidues were baised due to lack of proper random sequencing, improper employed blinding and no long term follow up. Therefore, more studies are required to compare all apexification materials with an appropriate allocation concealment, randomization technique, and blinding. Conclusion Based on the above studies evaluated, all the three materials had almost similar clinical success rates, radiographic success rates, and apical barrier formation rates. However, MTA and Endosequence BCRRM were associated with a significantly shorter time to achieve apical barrier formation than the calcium hydroxide. Although MTA and ERRM showed good results, there are only limited studies to evaluate MTA and ERRM. Hence, more comparative studies are required to prove the best material for apexification of immature permanent teeth. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest. References 1. Chueh LH, Ho YC, Kuo TC, Lai WH, Chen YH, Chiang CP. Regenerative endodontic treatment for necrotic immature permanent teeth. J Endod 2009;35:160‑4. 2. Huang  GT, Sonoyama  W, Liu  Y, Liu  H, Wang  S, Shi  S. The hidden treasure in apical papilla: The potential role in pulp/dentin regeneration and bioroot engineering J Endod 2008;34:645‑51. 3. Sheehy  EC, Roberts  GJ. Use of calcium hydroxide for apical barrier formation and healing in non‑vital immature permanent teeth: A review. Br Dent J 1997;183:241‑6. 4. Anthonappa  RP, King  NM, Martens  LC. Is there sufficient evidence to support the long‑term efficacy of mineral trioxide aggregate (MTA) for endodontic therapy in primary teeth? Int Endod J 2013;46:198‑204. 5. Damle SG, Bhattal H, Loomba A. Apexification of anterior teeth: A comparative evaluation of mineral trioxide aggregate and calcium hydroxide paste. J Clin Pediatr Dent 2012;36:263‑8. 6. Park M, Ahn BD. Immature permanent teeth with apical periodontitis and abscess treated by regenerative endodontic treatment using calcium hydroxide and MTA: A  report of two cases. Pediatr Dent 2014;36:107‑10. 7. Sarkar NK, Caicedo R, Ritwik P, Moiseyeva R, Kawashima I. Physicochemical basis of the biologic properties of mineral trioxide aggregate. J Endod 2005;31:97‑100. 8. Parirokh  M, Torabinejad  M. Mineral trioxide aggregate: A comprehensive literature reviewe Part III: Clinical applications, drawbacks, and mechanism of action. J Endod 2010;36:400‑13. 9. Krastl G, Allgayer N, Lenherr P, Filippi A, Taneja P, Weiger R. Tooth discoloration induced by endodontic materials: A literature review. Dent Traumatol 2013;29:2‑7. 10. Utneja S, Nawal RR, Talwar S, Verma M. Current perspectives of bio‑ceramic technology in endodontics: Calcium enriched mixture cement – Review of its composition, properties and applications. Restor Dent Endod 2015;40:1‑13. 11. Damas BA, Wheater MA, Bringas JS, Hoen MM. Cytotoxicity comparison of mineral trioxide aggregates and endoSequence bioceramic root repair materials. J Endod 2011;37:372‑5. 12. El Meligy  OA, Avery  DR. Comparison of apexification with mineral trioxide aggregate and calcium hydroxide. J Pediatr Dent 2006;28:248‑53. 13. Pradhan  DP, Chawla  HS, Gauba  K, Goyal  A. Comparative evaluation of endodontic management of teeth with unformed apices with mineral trioxide aggregate and calcium hydroxide. J Dent Child (Chic) 2006;73:79‑85. 14. Simon S, Rilliard F, Berdal A, Machtou P. The use of mineral trioxide aggregate in one‑visit apexification treatment: A prospective study. Int Endod J 2007;40:186‑97. 15. Neveu B, Bonte E, Baune B, Serreau S, Aissal F, Quinquis L, et al. Mineral trioxyde aggregate versus calcium hydroxide in apexification of non vital immature teeth: Study protocol for a randomized controlled trial. Trials 2011;12:174. 16. Bonte E, Beslot A, Boukpessi T, Lasfargues JJ. MTA versus Ca(OH)2 in apexification of non‑vital immature permanent teeth: A randomized clinical trial comparison. Clin Oral Investig 2015;19:1381‑8. 17. Lee LW, Hsieh SC, Lin YH, Huang CF, Hsiao SH, Hung WC. Comparison of clinical outcomes for 40 necrotic immature permanent incisors treated with calcium hydroxide or mineral trioxide aggregate apexification/apexogenesis. J  Formos Med Assoc 2015;114:139‑46. 18. Damle  SG, Bhattal  H, Damle  D, Dhindsa  A, Loomba  A, Singla S. Clinical and radiographic assessment of mineral trioxide aggregate and calcium hydroxide as apexification agents in traumatized young permanent anterior teeth: A  comparative study. Dent Res J 2016;13:284‑91. 19. Sarnowski A. Management of Open Apex Using a Bioceramic apical Barrier‑its Success and Survival Rates at Virginia Commonwealth University. VCU: Virginia Common Wealth University; 2019. 20. Barakat IF, Fethi A. Clinical and radiographical evaluation of bioceramic root canal sealer and MTA in apexification of immature permanent teeth. Egypt Dent J 2020;66:2057‑63. 21. Lin JC, Xuan Lu JX, Zeng Q, Zhao W, Li WQ, Ling JQ. Comparison of mineral trioxide aggregate and calcium hydroxide for apexification of immature permanent teeth: A  systematic review and meta‑analysis. J Formos Med Assoc 2016;115:523‑30. 22. Chala  S, Abouqal  R, Rida  S. Apexification of immature teeth with calcium hydroxide or mineral trioxide aggregate: Systematic review and meta‑analysis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2011;112:e36‑42. 23. Nicoloso GF, Pötter IG, Rocha RO, Montagner F, Casagrande L. A comparative evaluation of endodontic treatments for immature necrotic permanent teeth based on clinical and radiographic outcomes: A systematic review and meta‑analysis. Int J Paediatr Dent 2017;27:217‑27. 24. Duraivel D. Management of non vital teeth with open apex using endosequence root repair material, mineral trioxide aggregate and biodentin – A case series. J Conserv Dent 2014;17:340‑3. [Downloaded free from http://www.jpbsonline.org on Sunday, June 6, 2021, IP: 175.101.146.64]