Clinical Research
Influence of Age and Apical Diameter on the
Success of Endodontic Regeneration Procedures
Bishoy Safwat Estefan, BDS,* Kariem Mostafa El Batouty, PhD,* Mohamed Mokhtar Nagy, PhD,*
and Anibal Diogenes, DDS, MS, PhD†
Abstract
Introduction: Treatment of immature permanent teeth
with necrotic pulp and apical pathosis constitutes a chal-
lenge for endodontists. The present study was done to
T reatment of immature
evaluate the effect of age and apical diameter on the
regenerative potential of young permanent immature
teeth with necrotic pulps. Methods: Immature necrotic
permanent maxillary incisors (n = 40) of patients
9–18 years old were divided into 2 groups according
to the treatment protocol: group Y (younger age group),
9–13 years and group O (older age group), 14–18 years.
Each group was further subdivided into 2 subgroups ac-
cording to apical diameter, subgroup (n) (narrower
diameter) between 0.5 and 1 mm and subgroup (w)
(wider diameter) equal to or greater than 1 mm. Revas-
cularization procedures were performed for all patients.
Follow-up was done for up to 12 months. Standardized
radiographs were digitally evaluated for increase in root
length and thickness and decrease in apical diameter.
Results: After the follow-up period, most of the cases
demonstrated radiographic evidence of periapical heal-
ing. Group Y showed significant progressive increase in
root length and width and decrease in apical diameter.
Subgroup (w) representing wider apical diameter
showed significant progress as well. Conclusions: It
was found that revascularization procedures can be im-
plemented in any age ranging from 9 to 18 years; how-
ever, younger age groups were better candidates for
revascularization procedure than older ones. Regarding
the apical diameter, regeneration procedures were suc-
cessful with apical diameters as small as 0.5 mm. How-
ever, teeth with preoperative wider diameters ($1 mm)
demonstrated greater increase in root thickness, length,
and apical narrowing. (J Endod 2016;-:1–6)
Key Words
Age, apical diameter, regeneration
From the *Department of Endodontics, Faculty of Dentistry, Ain Shams University, Cairo, Egypt; and †Department of Endodontics, University of Texas Health Science
Center at San Antonio, San Antonio, Texas.
Address requests for reprints to Dr Mohamed Mokhtar Nagy, Department of Endodontics, Faculty of Dentistry, Ain Shams University, 14 Asmaa Fahmy Street,
Heliopolis, Cairo, Egypt. E-mail address: mmnagy80@gmail.com
0099-2399/$ - see front matter
Copyright ª 2016 American Association of Endodontists.
http://dx.doi.org/10.1016/j.joen.2016.06.020
JOE — Volume -, Number -, - 2016
permanent teeth with
necrotic pulp and apical
Significance
Pulp regeneration is a biologic treatment modality
for immature teeth with open apices. Regenerative
pathosis constitutes a
ability depends on both age and apical diameter.
challenge for endodon-
tists. Such cases are
commonly encountered in children because of trauma, dental anatomic variations
(eg, dens evaginatus), and untreated carious lesions. Many of these teeth develop pulpal
necrosis before completing root development. Such conditions are challenging not only
in root canal debridement and filling but also for the thin dentinal walls increasing the
risk of subsequent fracture (1).
Historically, immature apices have been managed with root-end closure through
apexification (2, 3). Although these procedures have excellent clinical success for the
resolution of infection and its associated symptoms, they do very little for continued root
development. Thus, teeth remain with thin dentinal walls after apexification procedures
(4). In addition, in highly immature teeth, clinician may elect the long-term use of cal-
cium hydroxide as the method to develop an apical calcific barrier. This technique has
several disadvantages because it requires multiple visits during long period of time,
requiring compliance, and the long-term use of calcium hydroxide might alter the me-
chanical properties of dentin, making the tooth more susceptible to fractures (5).
Therefore, even if apexification closure is successful, the long-term prognosis is ques-
tionable because of eventual root fracture (6).
Recently, the concept of immediate apical plug has been advocated. This technique
is performed by placement of artificial apical plug obliterating the apical portion of the
canal. Mineral trioxide aggregate (MTA) proved to be excellent candidate for this pro-
tocol. This protocol has the advantage of reduced number of visits, higher patient
compliance, and high success rate. However, the problem of thin brittle roots was
not solved (7–9).
An alternative approach to treating the immature necrotic permanent tooth is to
regenerate pulpal tissue, allowing for continued root formation. This treatment modality
was introduced as a biological alternative for continued maturation of the entire root
rather than the formation of an apical calcific barrier through apexification (10–12).
In regenerative endodontics, one of the goals is to promote continued root devel-
opment in addition to the crucial resolution of the disease process. Therefore, the
advantage of this treatment is continued root lengthening and reinforcement of lateral
dentinal walls with deposition of new hard tissue. Revascularization, regeneration, and
revitalization are commonly used terms to describe the regrowth of de novo tissue
within the root canal space (13–21).
Influence of Age and Apical Diameter on Regeneration 1
Clinical Research
It has been appreciated in the dental trauma literature that regen-
erative potential of the dental pulp in replanted immature teeth is influ-
enced by age, stage of root development, and apical diameter (22).
Because the patient’s age is directly related to stage of root formation
and apical diameter, it is likely a modifying factor in regenerative end-
odontic procedures. Thus, the aim of this study was to evaluate the effect
of age and the apical diameter on the outcomes of the regenerative
procedures.
Materials and Methods
Forty patients with immature, non-vital maxillary anterior teeth
presenting with or without signs and/or symptoms of periapical pathol-
ogy were included in this study from the outpatient clinic of the Faculty
of Dentistry, Ain Shams University, Cairo, Egypt. A detailed medical and
dental history was obtained from each patient’s parents or guardians.
Only systemically healthy patients were included in this research. The
clinical and radiographic exclusion criteria were teeth with vertical frac-
tures, periodontally involved teeth, and non-restorable teeth. All pro-
cedures were performed after obtaining proper institutional review
board approval that was based on the regulations of the Ethical Commit-
tee of the Faculty of Dentistry, Ain Shams University. Intraoral periapical
radiographs revealed immature apices. The age of the patients ranged
between 9 and 18 years. Informed consent including the proposed
treatment and possible outcomes or complications was signed for
each case by the patient’s parents or guardians.
Preoperative radiographs were acquired by using the standardized
paralleling technique with the Rinn XCP alignment system (Rinn Corpo-
ration, Elgin, IL). Periapical radiographs were digitized by using a trans-
parency scanner (HP Scanjet G3110; Hewlett-Packard Development Co,
Palo Alto, CA) for apical diameter measurement via ImageJ software
(ImageJ v1.44; National Institutes of Health, Bethesda, MD).
Cases were divided into 2 groups (20 patients for each group):
group Y (younger age group), aged 9–13 years; and group O (older
age group), aged 14–18.
Each group was subdivided according to apical diameter into 2
equal subgroups (n = 10): subgroup (n) narrower range, apical diam-
eter between 0.5 mm and 1 mm; and subgroup (w) wider range, apical
diameter equal to or greater than 1 mm.
Teeth were anesthetized by using local anesthesia without a
vasoconstrictor (Scandonest 3% plain; Septodont, Saint-Maur-Des-
Fosses, France). After rubber dam isolation, access cavities were pre-
pared, and root canals were irrigated by using 10 mL 2.6% sodium
hypochlorite, with circumferential filling of the canal walls by using
hand files. The triple antibiotic paste was prepared by using metro-
nidazole (500-mg tablets, Flagyl 500 mg; Aventis, Cairo, Egypt), cip-
rofloxacin (250-mg tablets, Ciprocin 250 mg; EPICO, Cairo, Egypt),
and doxycycline (100-mg capsules, Vibramycin; Pfizer, Cairo, Egypt).
The doxycycline capsule content was evacuated in a sterile mortar; a
tablet of metronidazole and a tablet of ciprofloxacin were crushed
and ground into homogenous powder in the same mortar by using
a pestle. Saline drops were added and mixed by using the pestle until
a creamy paste was achieved. The canal space was dried by using
paper points, and 1 mL prepared paste was injected into the canals
by using a sterile plastic syringe with a 20-gauge needle. A sterile cot-
ton pellet was then applied, and the access cavity was sealed by using
a temporary restoration (Coltosol F; Coltene Whaledent, Altstatten,
Switzerland) for 3 weeks. The final visit was scheduled when the
tooth was asymptomatic with no signs of discharge. In cases of
persistent infection, 1 or more visits were scheduled for further
drainage and chemical disinfection. After anesthesia and proper
isolation, the temporary restoration and the cotton pellet were
removed. The canal was irrigated with 10 mL NaOCl 2.6%, followed
by 17% EDTA for about 1 minute. Canals were then dried with sterile
paper points.
A sterile hand file size #50 was used with sharp strokes into the
periapical tissue 2 mm beyond the apex until bleeding was evident at
the cervical portion of the canal. An MTA orifice plug was used to
seal the canal orifice covered by a moist cotton pellet. After 1 week, ad-
hesive composite resin was used to seal the access cavity.
After treatment, patients were recalled for follow-up every 3
months for up to 1 year.
Evaluation
The clinical assessment of pain and/or swelling and standardized
radiographic assessment included the following:

TABLE 1. Summary of Patients’ Demographic Data

Group I Group II
Patient no. Tooth no. Age (y)/sex Follow-up (mo) Patient no. Tooth no. Age (y)/Sex Follow-up (mo)
Subgroup a
1 8 9/m 12 1 8 9/m 12
2 8 9/m 12 2 8 9/f 12
3 9 9/f 12 3 10 10/f 12
4 8 10/f 12 4 7 10/f 12
5 9 11/m 12 5 8 11/f 12
6 7 11/m 10 6 8 11/m 12
7 10 12/m 12 7 9 11/m 12
8 8 13/f 12 8 10 13/m 11
9 9 13/m Excluded 9 10 13/m Failed
10 8 12/m Excluded 10 7 11/f Excluded
Subgroup b
1 9 14/m 12 1 8 14/f 12
2 9 14/f 12 2 9 15/f 12
3 9 14/m 12 3 9 15/m 12
4 8 15/m 12 4 8 15/m 12
5 10 15/f 12 5 7 16/f 10
6 10 16/f 12 6 9 17/m 12
7 7 17/m 12 7 8 18/m 12
8 7 18/f 12 8 10 18/m 12
9 8 18/f Failed 9 10 18/m 10
10 9 17/m Excluded 10 10 15/f Excluded

2 Estefan et al. JOE — Volume -, Number -, - 2016

 Clinical Research

Figure 1. Representative cases. (A) Preoperative radiograph representing group O(n); (B) radiograph of same case in group O(n) after 12 months of follow-up;
(C) preoperative radiograph representing group O(w); (D) radiograph of same case in group O(w) after 12 months of follow-up; (E) preoperative radiograph
representing group Ia; (F) radiograph of same case in group Y(n) after 12 months of follow-up; (G) preoperative radiograph representing group Y(w);
(H) radiograph of same case in group Y(w) after 12 months of follow-up.

1. An increase in root length Increase in Root Length

2. An increase in root thickness A measuring scale was set in the ImageJ software (ImageJ v1.44)
3. A decrease in apical diameter by measuring a known clinical dimension to its radiographic dimen-
All measurements were performed blindly by 2 examiners and sion. The scale was calculated as the number of measured pixels per
averaged. millimeter length. Root lengths were measured as a straight line from

JOE — Volume -, Number -, - 2016 Influence of Age and Apical Diameter on Regeneration 3
Clinical Research
TABLE 2. Increase in Length in Millimeters for All Groups during Different Follow-up Periods
Group 3 months 6 months 9 months 12 months Overall
Ia 0.21  0.2a 0.18  0.12a 0.41  0.27a 0.29  0.18a 1.09  0.5a
Ib 0.36  0.28a 0.43  0.4b 0.25  0.21b 0.22  0.14a 1.26  1.08a
IIa 0.13  0.11b 0.17  0.1a 0.08  0.03c 0.05  0.02b 0.43  0.19b
IIb 0.12  0.1b 0.08  0.06a 0.15  0.1c 0.1  0.01b 0.45  0.3b
P value .02 .036 .007 #.001 #.001
Significant at P # .05. Different letters indicate significant difference.

the cementoenamel junction to the radiographic apex of the tooth in
millimeters. Pretreatment and follow-up root lengths were measured,
and the difference in root length was calculated (4). The percentage
of increase in length was calculated as follows:
Percentage of increase in length
postoperative length  preoperative length
¼  100
preoperative length
Increase in Root Thickness
By using the preset measurement scale, the level of the apical third
was determined and fixed from the cementoenamel junction. The root
thickness and the pulp width were measured at this level in millimeters.
Dentin thickness was measured by subtracting the pulp space from the
whole root thickness (4).
Measurements were performed preoperatively and postopera-
tively at the same fixed level. The difference in thickness was calculated.
The percentage of increase in dentin thickness was calculated as
follows:
Dentin Thickness ¼ root thickness  pulp width
Percentage of increase in thickness
postoperative thickness  preoperative thickness
¼  100
preoperative thickness
Sciences 20.0; IBM, Armonk, NY). Two-way analysis of variance was
performed. The Tukey post hoc test was used in case of significance.
Results
Patients’ demographic data are summarized in Table 1. A total of 5
patients were excluded from the study because of inadequate compli-
ance and failure to recall. Two cases were excluded from group
Y(n), 1 case was excluded from group Y(w), 1 case was excluded
from group O(n), and 1 case was excluded from group O(w). The per-
centages of recall for groups Y(n), Y(w), O(n), and O(w) were 80%,
90%, 90%, and 90%, respectively. Clinical and radiographic examina-
tion during the follow-up period showed signs and symptoms of failure
in 2 of the 35 recalled cases, with overall success rate of 94.3%. One
case belonged to group Y(w), and the other case belonged to group
O(n). The failed cases were reevaluated, and the treatment plan was
shifted to MTA apexification. Representative cases are shown in
Figure 1.
Increase in Root Length
Statistical analysis showed no significant difference between the
subgroups (n) and (w) in both age groups Y and O through the whole
follow-up period (Table 2). Younger age groups [Y(n) and Y(w)]
showed significantly greater increase (1.09  0.5 and 1.26 
1.08 mm, respectively) in root length than in older age groups [O(n)
and O(w)] (0.43  0.19 and 0.45  0.3 mm, respectively).

Decrease in Apical Diameter

Increase in Root Thickness
By using the preset measurement scale, the diameter of the apical
Statistical analysis demonstrated no significant difference between
foramen was measured in millimeters. Measurements were performed
the subgroups (n) and (w) in age group Y (increase 0.5  0.24 and
preoperatively and postoperatively. The difference in apical diameter
0.61  0.38 mm, respectively). However, in age group O subgroup
was calculated (23).
(n), a significantly lower increase in root thickness was observed
The percentage of apical closure was calculated as follows:
(0.14  0.11 mm) (Table 3).
Percentage of apical closure
postoperative apical diameterpreoperative apical diameter
¼ 100 Decrease in Apical Diameter
preoperative apical diameter
Group Y(w) showed the highest decrease in apical diameter at the
follow-up period, followed by group Y(n) and O(w). Conversely, group
Data were collected, tabulated, and statistically analyzed by using O(n) (older age group with narrower diameter) showed the least sig-
statistical analysis software SPSS (Statistical Packages for the Social nificant change in apical diameter (Table 4).

TABLE 3. Increase in Thickness in Millimeters for All Groups during Different Follow-up Periods
Group 3 months 6 months 9 months 12 months Overall
Ia 0.09  0.09 a
0.08  0.07 a
0.04  0.02 a
0.29  0.18 a
0.5  0.24a
Ib 0.09  0.08a 0.19  0.13b 0.11  0.09b 0.22  0.14a 0.61  0.38a
IIa 0.02  0.01b 0.05  0.02a 0.02  0.02c 0.05  0.02b 0.14  0.11b
IIb 0.18  0.16c 0.11  0.12b 0.06  0.03c 0.1  0.01b 0.45  0.23a
P value .004 .027 .002 .015 #.001
Significant at P # .05. Different letters indicate significant difference.

4 Estefan et al. JOE — Volume -, Number -, - 2016


TABLE 4. Decrease in Apical Diameter in Millimeters for All Groups during Different Follow-up Periods
Group 3 months
Ia 0.11  0.09a
Ib 0.27  0.22a
IIa 0.03  0.02c
IIb 0.18  0.17a
P value .0031
Significant at P # .05. Different letters indicate significant difference.
Discussion
Endodontic treatment of immature permanent teeth with necrotic
pulp, with or without apical pathosis, poses several clinical challenges
(1). There is a risk of inducing dentin wall fracture or extending gutta-
percha or other restorative materials into the periapical tissue during
compaction of the root canal filling. Recently, regenerative endodontics
has gained much attention as a biologically based treatment alternative.
Regenerative approaches differ from apexification procedures in that
they can allow for further root maturation in length and thickness by
regenerated vital tissue (10–12).
Thorough disinfection of the root canal that is followed by stimu-
lation of residual stem cells gave the way to ingrowth of de novo pulp-
like tissue (revascularization procedure), which can induce formation
of new hard tissue on the existing dentin wall and continued root devel-
opment (14). Revascularization is considered a simple protocol by
which pulp regeneration is enhanced by the use of the blood clot as
a scaffold for autogenous release stem cells, as stated by Lovelace
et al (24).
The outcome of revascularization procedures remains somewhat
unpredictable and multifactorial. The aim of this study was to evaluate
the effect of preoperative apical diameter and age on the outcomes of
regenerative endodontic procedures. The evaluation was based on
the increase in root length thickness and the decrease in apical diam-
eter. The choice of age as a factor represented the healing capacity of the
patient, whereas the apical diameter can be a limiting factor for allowing
the influx of stem cells and apical blood vessels into the newly formed
tissue (22).
Disinfection of the root canal used the disinfection protocol
described by Sato et al (25) and Hoshino et al (26), which was adopted
in many studies implementing the revascularization procedures. The
use of the triple antibiotic paste in this study resulted in resolution of
the disease within 3 weeks in the great majority of patients (33 patients).
However, there were some patients who required additional application
of the medication (7 patients), and some patients who had systemic
manifestation of the infection had to take orally administered antibi-
otics. In addition, 17% EDTA was used to remove the smear layer, which
allowed for better cell adhesion to dentin and enhanced the release of
the dentin growth factors (27, 28).
The increase in root length and thickness among all groups was
noticed after 1-year follow up in most of the cases with variable records.
The root length was increased probably via the deposition of mineral-
ized tissue along the dentinal walls, which might be intracanal
cementum or bone-like tissue as stated by many authors (16, 23).
However, the nature of the tissues formed was not evaluated in this
study, which focused on clinical outcomes. Nonetheless, the younger
age group showed significant increase in length independent of the
apical diameter when compared with older age group. This might be
attributed to greater stem cell regenerative potential seen in younger
individuals (29, 30).
The results on the increase in root thickness were similar to the
root length results except for the older age group with wider apical
JOE — Volume -, Number -, - 2016
Clinical Research
6 months 9 months 12 months Overall
0.06  0.05a 0.11  0.04a 0.14  0.11a 0.42  0.24a
0.29  0.13b 0.32  0.21b 0.23  0.14a 1.11  0.56a
0.02  0.02a 0.03  0.02c 0.05  0.04c 0.13  0.09c
0.09  0.07a 0.19  0.13a 0.22  0.16a 0.68  0.41a
.048 .012 .005 #.001
diameter, which were similar to the younger age group. The older group
with narrower diameter was significantly lower in root thickness in-
crease. This might indicate the apical diameter is a second factor gov-
erning the progress of revascularization process. The new tissue such as
cementum or bone itself would not grow into the canal space through
the apical foramen. Cementoblasts or osteoblasts migrate into the canal
space and produce cementum or bone. The sizes of cementoblasts and
osteoblasts (10–100 mm) are much smaller than those of many blood
vessels entering the apical foramen.
Thus, the apical diameter at the time of treatment completion ap-
pears to be a strong predictor of root development. Also, it was found
that the greatest narrowing of the apical diameter occurred in the
younger patients. For the older patient group, the narrowing was
more limited than in the younger patients, and it occurred more predict-
ably when the apical diameter was greater than 1 mm preoperatively.
Conclusions
Under the circumstances of this study, it was found that revascu-
larization procedures can be implemented in any age ranging from 9
to 18 years; however, younger age groups were better candidates for
revascularization procedures than older age groups. Regarding the api-
cal diameter as the second factor in the predictability of the procedure
outcomes, regeneration procedures were successful with apical diam-
eters as small as 0.5 mm. However, teeth with preoperative wider diam-
eters ($1 mm) in both groups demonstrated greater increase in root
thickness, length, and apical narrowing.
Acknowledgments
The authors deny any conflicts of interest related to this study.
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