Clinical Research

Regenerative Endodontics Versus Apexification

in Immature Permanent Teeth with Apical
Periodontitis: A Prospective Randomized
Controlled Study
Jiacheng Lin, PhD,* Qian Zeng, PhD,† Xi Wei, PhD,† Wei Zhao, PhD,* Minyi Cui, PhD,‡
Jing Gu, PhD,§ Jiaxuan Lu, PhD,* Maobin Yang, DMD, MDS, PhD,k and Junqi Ling, PhD¶

Abstract
Introduction: The aim of the study was to compare the
outcomes of regenerative endodontic treatment (RET)
and apexification on immature permanent teeth with
pulp necrosis and apical periodontitis. Methods: A total
of 118 patients (118 teeth) were recruited and randomly
assigned to either RET or apexification treatment. Each
treatment group was divided into 2 subgroups according
to the etiology: dens evaginatus or trauma. Clinical
symptoms and complications were recorded, and
cone-beam computed tomographic imaging with a
limited field of view was used to measure the change
of root length, root thickness, and apical foramen size
at the 12-month follow-up. The t test/rank sum test
and Fisher exact test were applied to compare the
change of root morphology between RET and apexifica-
tion. Results: One hundred three of 118 cases were
completed at the 12-month follow-up. The survival
rate was 100% for both treatment groups. All cases
were asymptomatic with apical healing. The RET group
showed a significant increase in root length and root
thickness compared with the apexification group
(P < .05). In the RET group, the cases caused by dens
evaginatus achieved increased root length and root
thickness compared with those caused by trauma
(P < .05). Conclusions: RET and apexification achieved
a comparable outcome in regard to the resolution of
symptoms and apical healing. RET showed a better
outcome than apexification regarding increased root
thickness and root length. The etiology had an impact
on the outcome of RET. Dens evaginatus cases showed
better prognoses than trauma cases after RET. (J Endod
2017;-:1–7)
Key Words
Apexification, apical periodontitis, cone-beam computed tomography, immature teeth,
regenerative endodontics
I mmature teeth with pulp
necrosis and apical peri-
odontitis have been a
Significance
This clinical randomized controlled study compared
the outcomes of RET and apexification. The results
challenge for endodontic
showed a high success rate of the RET group at
treatment because of the
the 12-month follow-up. Dens evaginatus cases
thin root wall and open
showed better prognoses than trauma cases upon
apex. These cases are usu-
RET treatment.
ally caused by trauma,
caries, or a developmental
malformation, such as dens evaginatus or dens invaginatus (1–4), resulting in pulp
necrosis and arrested root development. Apexification is a conventional treatment
modality for these cases in which either calcium hydroxide paste is used to induce
an apical barrier or mineral trioxide aggregate (MTA) is placed as an apical barrier
in order to achieve closure of the apex. Although the success rate of apexification
has been reported to be between 74% and 100%, it may result in abnormal root
morphology such as the formation of calcified tissue inside the root canal (5), and
long-term calcium hydroxide placement may weaken the dentin and induce root frac-
ture (6).
Regenerative endodontic treatment (RET) provides a new treatment modality for
the previously described cases. In the 1960s, Dr Nygaard-Ostby (7) first raised the
concept of tissue regeneration inside the root canal. In 2004, Drs Banchs and Trope
(8) introduced a modified clinical regenerative endodontic protocol that involved
minimal instrumentation, copious irrigation, and placement of antibiotic paste as in-
tracanal medicament followed by inducing bleeding and the formation of a blood clot
inside the root canal. In addition to a blood clot, autologous platelet-rich plasma and
platelet-rich fibrin were also introduced into the root canal as alternative scaffolds
because of the fact that platelet-rich plasma and platelet-rich fibrin contained mole-
cules that could potentially induce tissue regeneration (9–11). In 2016, the American

From the *Department of Pediatric Dentistry, †Operative Dentistry and Endodontics, ‡Department of Radiology, Guanghua School of Stomatology, Affiliated Sto-
matological Hospital, Guangdong Provincial Key Laboratory of Stomatology, §Department of Medical Statistics and Epidemiology, School of Public Health, and
¶
Guanghua School of Stomatology, Affiliated Stomatological Hospital, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou,
Guangdong, China; and kDepartment of Endodontology, Kornberg School of Dentistry, Temple University, Philadelphia, Pennsylvania.
Address requests for reprints to Dr Junqi Ling, Affiliated Stomatological Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510055, China, or Dr Maobin
Yang, Department of Endodontology, Kornberg School of Dentistry, Temple University, Philadelphia, PA 19140. E-mail address: lingjq@mail.sysu.edu.cn or myang@
temple.edu
0099-2399/$ - see front matter
Copyright ª 2017 American Association of Endodontists.
http://dx.doi.org/10.1016/j.joen.2017.06.023

JOE — Volume -, Number -, - 2017 Regenerative Endodontics vs Apexification 1

Clinical Research
TABLE 1. Cases Recruited in the Regenerative Endodontic Treatment (RET) and Apexification Groups
RET
Tooth types Premolar Central incisor
Etiology Dens evaginatus Trauma
Original case (n) 53 27
Lost case (n) 5 6
Final case (n) 48 21
(12-month follow-up)
Association of Endodontists proposed a standard protocol for
regenerative endodontic procedures (12). To date, numerous case re-
ports and cases series showed ‘‘success’’ of RET, which was defined as
the disappearance of the periapical lesion and continued root devel-
opment.
Comparison of the success rate between apexification and RET has
been reported in several retrospective and prospective studies (13–18)
although the result is still inconclusive because of the variable study
designs and limited sample numbers. A clinical randomized study
with a larger size of samples is needed. In some RET cases,
complications such as external root resorption and discoloration
were noticed but never systematically analyzed (14). The aim of this
study was to compare the outcomes of RET and apexification on imma-
ture permanent teeth with pulp necrosis and apical periodontitis.
Materials and Methods
Patient Recruitment and Randomization
This study was approved by the Ethics Committee of the Affiliated
Hospital of Stomatology, Sun Yat-sen University, Guangzhou, Guang-
dong, China, and registered in ClinicalTrials.gov (ID: NCT01799187).
Patients were recruited from the Department of Pediatric Dentistry of
the dental hospital from June 2013 to May 2015. The inclusion criteria
were as follows: patients between 6 and 18 years old; pulp necrosis,
which was defined by a negative response to the temperature test and
the electric pulp test; radiographic evidence of immature teeth with a
single canal, open apices larger than 1 mm in diameter, and presence
of periapical radiolucency; and the involved tooth had either dens eva-
ginatus or a history of trauma. The exclusion criteria were patients with
chronic systematic disease, patients allergic to the antibiotics used in the
study, a vital tooth, a tooth with periodontal disease, a tooth with more
than 1 canal, and radiographic evidence of a root fracture. Envelopes
containing information on RET or apexification were prepared with a
ratio of 2 to 1 and randomly assigned to the patients. All the clinical pro-
cedures were performed by 1 experienced endodontist who also had
special training in pediatric dentistry.
Regenerative Endodontic Procedure
After local anesthesia with 2% lidocaine (no epinephrine [Lido-
caine Hydrochloride Injection; Hubei Tiansheng Kangdi Pharmaceu-
tical Co Ltd, Hubei Sheng, China]), the tooth was isolated with a
rubber dam, and access was performed with a #4 round bur. The canal
TABLE 2. Baseline of the Root Morphology Measured by Cone-beam Computed Tomographic Imaging (Preoperative)
Indexes (mm) RET (n = 69)
Size of apical foramen 2.11  0.86
Root length 11.60  1.17
Root thickness 1.41  0.02
*The t test/rank sum test.
2 Lin et al.
Apexification
Premolar Central incisor
Total Dens evaginatus Trauma Total Total
80 23 15 38 118
11 2 2 4 15
69 21 13 34 103
was then irrigated with 20 mL 1.5% sodium hypochlorite solution (Tan-
xiao Fengwei Pharmaceutical Co Ltd, Guangdong Province, China),
0.9% physiological saline, and 20 mL 17% EDTA (Zhongnan Reagent
Industry Co Ltd, Hunan Province, China). The canal was dried with a
paper point, and 0.1 mg/mL triple antibiotic paste was delivered into
the canal with a Lentulo spiral in which ciprofloxacin (Sigma-Aldrich,
St Louis, MO), metronidazole (Sigma-Aldrich), and clindamycin hydro-
chloride (Sigma-Aldrich) were equally mixed with distilled water. The
tooth was temporarily sealed with Caviton (GC Corporation, Tokyo,
Japan).
After 3 weeks, patients presented for the second visit. If the
symptom was not relieved, root canals were remedicated with triple
antibiotic paste for another 3 weeks. The asymptomatic tooth pro-
ceeded to the next step of RET treatment. After local anesthesia
with 2% lidocaine (no epinephrine) and rubber dam isolation, the
tooth was reaccessed. The triple antibiotic paste was removed with
0.9% saline, and 20 mL 17% EDTA solution was applied to the canal;
after this, the canal was dried with paper points. Bleeding was
induced by overinstrumenting with a #25 file and allowed to reach
3–4 mm below the cementoenamel junction (CEJ) to form a blood
clot. An absorbable collagen barrier (Heal-all Biological Membrane;
Zhenghai Biological Technology Co Ltd, Shandong Province, China)
was placed on top of the blood clot followed with white MTA (Pro-
Root MTA White; Dentsply International, Inc, Konstanz, Germany).
Then, the tooth was sealed with glass ionomer cement (GlasIonomer
FX-II; Shofu Inc, Kyoto, Japan). After 7 days, the glass ionomer
cement was removed, and the set of MTA was confirmed. The tooth
was finally restored with composite resin (Z350; 3M ESPE, St Paul,
MN).
Apexification Procedure
Local anesthesia was performed with 2% lidocaine. The tooth was
isolated with a rubber dam, and pulp access was performed. The canal
was irrigated with 20 mL 1.5% sodium hypochlorite and 0.9% physio-
logical saline followed by 20 mL 17% EDTA. After being dried with paper
points, calcium hydroxide paste was placed into the canal, and the tooth
was temporarily sealed with Caviton.
One week later, the tooth was reaccessed after isolation with a rub-
ber dam. Calcium hydroxide paste was removed using 17% EDTA irri-
tation. The root canal was dried with paper points, and Vitapex paste
(Neo Dental International, Inc, Tokyo, Japan) was injected into the ca-
nal before the tooth was sealed with glass ionomer cement. During the
Apexification (n = 34) P value*
2.02  0.82 .882
11.39  1.69 .912
1.43  0.04 .962
JOE — Volume -, Number -, - 2017

TABLE 3. Clinical Symptoms and Root Canal Morphology at the 12-month Follow-up
Resolution of
Asymptomatic, radiolucency,
Treatment n (%) n (%)
RET (n = 69) 69 (100) 69 (100)
Apexification (n = 34) 34 (100) 34 (100)
follow-up visit, once radiographic evidence of an apical barrier was
confirmed, the tooth was reaccessed, and the canal was obturated
with warm gutta-percha and restored with composite resin.
Follow-up Observation and Measurement
Periapical radiographic and limited field of view cone-beam
computed tomographic (CBCT) (PHT-6500; Vatech Co, Ltd,
Gyeonggi-do, Korea [90 kV and 7.0 mA]) images were taken before
treatment. The patients were scheduled to follow up at 3, 6, 9, and
12 months after the completion of therapy. Clinical symptoms such
as pain, swelling, sinus tract, mobility, tooth discoloration, and the oc-
clusion relationship were recorded, and a periapical radiograph was
taken every 3 months. At the 12-month follow-up, CBCT images were
taken to quantitatively analyze the root development. In this study, treat-
ment success was defined as the elimination of symptoms, the disap-
pearance of apical radiolucency with an increase of root length or a
decrease of the apical foramen, or both. We regarded cases as failures
if 1 of the following was present: the presence of clinical symptoms
(pain, swelling, or sinus tract), no change in root length or apical
size, recurrence of apical periodontitis, and external root resorption.
The failed cases and the complications including discoloration and
calcification in the RET group were recorded.
Root length, root thickness, and apical foramen size were
measured using CBCT imaging by 1 experienced oral radiologist using
the Ez3D2009 software according to the standardized protocol of the
manufacturer. Briefly, axial planes x, y, and z were used to determine
Figure 1. Two representative cases of RET showed the apical radiolucency disappeared and the root developed gradually. (A–E) Case 1 and (F–J) case 2. (A and F)
Preoperative radiographs, (B and G) 3-month follow-up, (C and H) 6-month follow-up, (D and I) 9-month follow-up, and (E and J) 12-month follow-up.
JOE — Volume -, Number -, - 2017
Clinical Research
Increase of
root length, Increase of root Apex closure, Survival rate,
n (%) thickness, n (%) n (%) n (%)
56 (81.16) 57 (82.60) 46 (65.21) 69 (100)
9 (26.47) 0 (0) 28 (82.35) 34 (100)
the central location of the measurement. The x axial plane was parallel
to the long axis of the teeth with the buccal tip and lingual tip on the
plane. The y axial plane was perpendicular to the x axial plane and
went across the maximum diameter of the pulp from the mesiodistal di-
rection. The z axial plane was perpendicular to both the x and y axial
planes and connected the top of the alveolar ridge crest mesially and
distally to the teeth. The distance between the CEJ and the apical end
point was measured distally and mesially, which was then averaged as
the root length. Root thickness was measured at 4, 6, and 8 mm
from the CEJ at the distal, mesial, buccal, and lingual positions, and
the average values were achieved using CBCT imaging. The size of the
apical foramen was averaged from the values of the buccolingual and
mesiodistal directions in CBCT imaging (Supplemental Figures S1
and S2 are available online at www.jendodon.com). In apexification
cases, the apical foramen size was recorded as 0 if the apical barrier
formed.
Statistical Analysis
The changes in root length, root thickness, and size of the apical
foramen were expressed as the average  standard deviation of the
mean and compared with the t test/rank sum test. The Fisher exact
test was used to explore if etiology would affect the outcome of RET
or apexification treatment. All data were analyzed using SPSS Statistics
17.0 for Windows (SPSS Inc, Chicago, IL), and P < .05 was regarded
as statistically significant.
Regenerative Endodontics vs Apexification 3
Clinical Research

Figure 2. Two representative cases of apexification treatment showed that the apical radiolucency disappeared and the apical barrier finally formed. (A–E) Case 1
and (F–J) case 2. (A and F) Preoperative radiographs, (B and G) 3-month follow-up, (C and H) 6-month follow-up, (D and I) 9-month follow-up, and (E and J)
12-month follow-up.

Results crease in root length (1.64  1.43 mm vs 0.60  1.06 mm) and
A total of 118 patients (118 teeth) were recruited in this study. The root thickness (0.24  0.25 mm vs 0.08  0.21 mm) but less of a
age of the patients ranged from 8–16 years old, with an average age of decrease in the size of the apical foramen (1.49  0.96 mm vs
10.50 years old (standard deviation = 1.80). The teeth were randomly 1.85  0.67 mm) (P < .05). To analyze the relationship of etiology
assigned to RET and apexification groups with a 2:1 ratio. A total of 80 and treatment outcome, each treatment group was divided into 2 sub-
teeth (27 central incisors and 53 premolars) were assigned to the RET groups, trauma and dens evaginatus. The results showed that for the
group, and a total of 38 teeth were assigned to the apexification group cases caused by dens evaginatus, RET significantly increased the root
(15 central incisors and 23 premolars). During the follow-up, 11 RET length and root thickness in comparison with apexification treatment
cases and 4 apexification cases were lost or quit. Therefore, a total of (P < .05) (Table 5). For the cases caused by trauma, only the increase
103 teeth completed the study, including 69 RET cases (21 central in- in root thickness showed a significant difference with RET compared
cisors and 48 premolars) and 34 apexification cases (13 central inci- with apexification treatment (P < .05) (Table 5).
sors and 21 premolars) (Table 1). In regard to the etiology, all 69 To better evaluate the treatment outcomes, root morphology was
premolar cases were caused by dens evaginatus, whereas all 34 central classified into the following 4 types based on the changes in root length
incisor cases were caused by trauma (Table 1). Before the treatment, and apical foramen size at the 12-month follow-up (Table 6): type I,
root length, root thickness, and the size of the apical foramen were continued root maturation and a decrease in apical foramen size;
measured by CBCT imaging, and the parameters on baseline were com- type II, increased root length but no change in apical foramen size;
parable between the 2 groups (Table 2). type III, no increased root length but a decrease in the size of the apical
At the 12-month follow-up, all the teeth survived (100% survival foramen; and type IV, no significant root length increase or decrease in
rate) and were asymptomatic (100%). The periapical lesions disap- the size of the apical foramen. We regarded types I, II, and III as effective
peared in all cases (100%). The cases with a root length increase, a outcomes and type IV as failure. The results showed that for the cases
root thickness increase, or apex closure are shown in Table 3. In the caused by dens evaginatus and treated with RET, type I was the most
RET group, 81.16% and 82.60% cases achieved an increased root
length and root thickness, respectively, whereas 65.21% cases showed TABLE 4. Quantitative Changes of Root Morphology at the 12-month Follow-
apex closure (Table 3). Two successful cases of RET treatment are up Measured by Cone-beam Computed Tomographic Imaging
shown in Figure 1A–J. In the apexification group, only 9 cases Root changes RET Apexification P
(26.47%) showed increased root length, whereas no case showed (mm) (n = 69) (n = 34) value*
increased root thickness, and 28 cases (82.35%) showed apex closure Increase of root length 1.64  1.43 0.60  1.06 < .001†
by the formation of a calcification barrier. Figure 2A–J shows 2 repre- Increase of root thickness 0.24  0.25 0.08  0.21 < .001†
sentative cases with apexification treatment. Decrease of apical 1.49  0.96 1.85  0.67 .033‡
The changes in root length, root thickness, and the size of the api- foramen size
cal foramen at the 12-month follow-up were quantitatively calculated *The t test/rank sum test.
based on the measurement from CBCT imaging (Table 4). Compared †
P < .001
with the apexification group, the RET group showed a significant in- ‡
P < .05.

4 Lin et al. JOE — Volume -, Number -, - 2017


TABLE 5. Root Changes in the Dens Evaginatus and Trauma Groups at the 12-month Follow-up
Dens evaginatus group
Root changes (mm) RET (n = 48) Apexification (n = 21)
Decrease of apical 1.58  1.00 1.95  0.71
foramen
Increase of root length 2.06  1.29 0.77  1.19
Increase of root thickness 0.26  0.27 0.09  0.19
*The t test/rank sum test.
†
P < .001
‡
P < .05.
common (91.6%), whereas types II, III, and IV (failure) were rare
(6.3%, 0%, and 2.1%, respectively). For those cases caused by trauma
and treated with RET, the outcomes of root morphology were almost
evenly distributed into the 4 types. A significant difference was found be-
tween these 2 subgroups (P < .05) (Table 7).
For the RET group, 6 cases in the trauma group and 1 case in the
dens evaginatus group did not show any continued root development
and were classified as type IV (failure). External root resorption was
found in 2 cases; both were in the trauma group (Fig. 3A–E). In the
RET cases with successful outcomes, discoloration and calcification
were the 2 main complications. A total of 30 RET cases showed discol-
oration, mainly occurring in the first 3 months after treatment, whereas
diffused calcification was found in 26 RET cases, the majority of which
occurred at the 6-month follow-up (Fig. 4A–E).
Discussion
RET and apexification are 2 treatment modalities for an immature
tooth with pulp necrosis and apical periodontitis. The success rate of
RET and apexification have been reported in several clinical studies
(13, 14, 16, 17). Calcium hydroxide and MTA have been used for
apexification. One-session apexification using MTA could build an arti-
ficial barrier without any change of the root, whereas apexification with
calcium hydroxide could achieve a calcification barrier, which may
contribute to an increased root length. To better evaluate the effect
on root development of RET, we chose the apexification technique (cal-
cium hydroxide) as the control group in the present study. In order to
compare the success rate between RET and apexification, it is critical to
define the criteria for ‘‘success.’’ The definition of success depends on
which level of the goals of treatment has been achieved. RET and apex-
ification have the same primary goal—elimination of symptoms with ev-
idence of bony healing. Therefore, it is straightforward to make a
comparison of success rates between RET and apexification based on
the primary goal, and most previous studies did so (13, 14, 16, 17).
The secondary goals of RET and apexification are different; RET is to
promote the continued formation of root, evidenced by the increased
root wall thickness and/or increased root length, whereas the
secondary goal for apexification is to form the apical barrier, with no
or less intent to promote continued root development (19–23).
Because of this difference, it is difficult to make a direct comparison
on the success rate between RET and apexification based on the
TABLE 6. Classification of Root Morphology at the 12-month Follow-up
Types Root length Apical foramen size
I Increased Decreased
II Increased Unchanged
III Unchanged Decreased
IV Unchanged Unchanged
JOE — Volume -, Number -, - 2017
Clinical Research
Trauma group
P value* RET (n = 21) Apexification (n = 13) P value*
.084 1.30  0.86 1.68  0.59 .176
<.001 †
0.68  1.29 0.31  0.75 .112
<.001† 0.19  0.18 0.08  0.26 .020‡
secondary goal, especially when the achievement of the secondary
goal (root morphology) is judged only by 2-dimensional radiography.
In present study, we used CBCT imaging to accurately measure the
change of root morphology, and we combined the primary goal and sec-
ondary goal to define the success (ie, the elimination of symptoms and
the disappearance of apical radiolucency with either an increased root
length or a decreased apical foramen). Although the results showed that
the overall success rate was 89.8% in the RET group and 97% in the
apexification group, the advantages of RET over apexification was
noticed because RET significantly promoted increased root length
and decreased apical foramen size (type I).
Radiographic images have been used to evaluate the outcome of
root morphology. The parameter radiographic root area is recommen-
ded (24), which requires not only the paralleling technique but also
taking x-rays from the exact same angle on preoperation and postoper-
ation. Compared with the 2-dimensional image, 3-dimensional data
offer valuable insights into the outcome for teeth treated with RET
(25). CBCT imaging provides 3-dimensional images of roots, canals,
and the apical area with high resolution as well as accurate measure-
ment on the root canal and periapical area (26, 27). In the present
study, we applied limited field of view CBCT imaging to measure the
changes in the root. The scope of CBCT radiation was limited to
target the tooth and the adjacent teeth to minimize the radiation
exposure. CBCT imaging provided not only accurate measurement on
the tooth development and healing of the apical lesion but also
additional information such as the calcification that occurred inside
canals, therefore offering better measurement than x-ray
radiography. In this clinical research, CBCT imaging was used as a
tool to provide better assessment of the outcomes, and the use of
CBCT imaging was approved by the ethics committee for this
research project only. For clinical practice, because of the
consideration of radiation dosage, we do not encourage using CBCT
imaging routinely to evaluate the outcome. The guidelines (the
American Association of Endodontists and the American Academy of
Oral and Maxillofacial Radiology joint statement) should be followed,
and the abuse of CBCT imaging on patients should be avoided.
In the RET group, different morphologies of the root apical
portion were found at the 12-month follow-up. Chen et al (28) reported
5 types of root morphology in 20 RET cases:
1. The thickness of the canal wall increased, and the root continued to
mature.
2. The root did not significantly develop, and the root apex became
blunt and closed.
3. The root continued to develop, but the apical foramen remained
open.
4. Severe calcification was formed in the canal space.
5. A hard tissue barrier was formed in the canal space between the cor-
onal MTA and the root apex including the scenario of severe calci-
fication in the canal space.
Regenerative Endodontics vs Apexification 5
Clinical Research
TABLE 7. Outcomes of Root Morphology in the Regenerative Endodontic Treatment (RET) and Apexification Groups
RET Apexification
Types Dens evaginatus (n = 48) Trauma (n = 21) Dens evaginatus (n = 21) Trauma (n = 13)
I 44 (91.6%) 7 (33.3%) 7 (33.3) 2 (15.4)
II 3 (6.3%) 2 (9.5%) 0 0
III 0 6 (28.6%) 14 (66.7) 10 (76.9)
IV 1 (2.1%) 6 (28.6%) 0 1 (7.7)
Success rate (%) 97.9* 71.4 100 92.3
Overall success rate (%) 89.8 97
Types I, II, and III were regarded as successes.
*A significant difference than the trauma group in the same treatment group.

In the present study, we did not consider 4 and 5 as success or
failure. Instead, we focused on change of the root morphology, specif-
ically the changes of root length and the size of the apical foramen. We
established 4 types of outcomes: type I, continued root maturation and a
decrease in apical foramen size; type II, increased root length but no
change in apical foramen size; type III, no increased root length but
a decrease in the size of the apical foramen; and type IV, no significant
root length increase nor decrease in the size of the apical foramen.
Among these 4 types, type I was regarded as the ideal outcome, and
type IV was defined as failure. Types I, II, and III were recognized as
a ‘‘successful’’ outcome when there was no recurrence of apical peri-
odontitis or external root resorption.
Developmental malformation, trauma, and caries were the 3 most
common causes of immature teeth that developed pulp necrosis and api-
cal periodontitis. In order to analyze the effect of etiology on the outcome,
we recruited the teeth that were caused by dens evaginatus or trauma. Af-
ter RET, 91.6% of cases showed type I in the dens evaginatus group,
whereas only 33.3% of cases were shown in the trauma group, indicating
that the dens evaginatus group had better prognoses than the trauma
group when treated by RET. After apexification treatment, type III was
the most common outcome in both the evaginatus and trauma groups
(66.7% and 76.9%, respectively), and only 33% and 15.4% of type I
was seen in the dens evaginatus group and trauma group, respectively.
This finding was consistent with a previous case reported by Cehreli
et al (2) in which trauma was found to induce root resorption and
may cause damage to the Hertwig epithelial root sheath as well as the api-
cal papilla, resulting in the failure of regenerative therapy. One limitation
of the present study was it coincidentally happened that all the recruited
central incisors were caused by trauma and all the premolars were caused
by dens evaginatus. The potential effect of tooth type on the outcome could
be a confounding variable that was not analyzed in the present study.
Calcification and discoloration in the root canal are 2 major com-
plications of RET treatment reported by previous case studies (29), and
both were found in our study. A total of 26 RET cases showed calcifica-
tion, mainly occurring at the 6-month follow-up. The calcified tissue in
the root canal may partly be caused by the use of MTA as a sealing ma-
terial (30) or other unknown reasons. Discoloration was also found in
30 RET cases. The majority of them were detected as early as the first
3 months and mainly occurred in the teeth cervix area. Kohli et al
(31) reported that MTA (both white and gray) and triple antibiotic paste
caused teeth discoloration. In the present study, discoloration was un-
likely to be caused by the root canal medication, but MTA as minocy-
cline was not used. It is suggested that materials such as
EndoSequence Root Repair Material (Brasseler USA, Savannah, GA),
EndoSequence Root Repair Material Fast Set Paste (Brasseler USA),
and Biodentine (Septodont, Saint-Maur-des-Fosses, France) should
be considered to prevent teeth discoloration.
In conclusion, the outcomes of RET and apexification were eval-
uated based on the morphology of the apical root and measured using
CBCT imaging. The etiology had an impact on the outcome of RET treat-
ment. Dens evaginatus cases showed better prognoses than trauma
cases upon RET treatment. Although about a 90% success rate has
been observed in the RET group at the 12-month follow-up and a
100% survival rate was found in both the RET and apexification groups
in the present study, failure cases have been reported beyond 12 months
by a previous study (17). A longer follow-up of the patients in our study
should be performed in order to provide better evaluation on the
changes of the success rate, survival rate, and complications.

Figure 3. Progressive external root resorption in the anterior tooth occurring after RET in a case with trauma history. (A) Preoperative radiography, (B) 3-month
follow-up, and (C) 6-month follow-up. External root resorption was noted (red arrow). (D) The external root resorption was progressively developed at the
9-month follow-up. (E) The root resorption was continuously developed almost at the 12-month follow-up. The red arrow shows the field where the external
root resorption occurred.

6 Lin et al. JOE — Volume -, Number -, - 2017


Figure 4. Diffused intracanal calcification in the root canal of a tooth with trauma history after RET treatment. (A) Preoperative radiography, (B) 3-month follow-
up, and (C) 6-month follow-up. An intracanal calcification was noted (red arrow). (D) The calcification became diffused in the root canal at 9 months. (E) The
diffused intracanal calcification at the 12-month follow-up. The red arrow shows the field where the calcification occurred.
Acknowledgments
Jiacheng Lin and Qian Zeng contributed equally to this study.
The authors gratefully thank Dr Lusai Xiang for reconstructing
the CBCT images.
Supported by the Sun Yat-sen University Clinical Research
5010 Programme (no. 2012016).
The authors deny any conflicts of interest related to this study.
Supplementary Material
Supplementary material associated with this article can be
found in the online version at www.jendodon.com (http://dx.doi.
org/10.1016/j.joen.2017.06.023).
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