Injuries to Permanent Dentition Symposium

Treatment Options: Apexogenesis and Apexification

Shahrokh Shabahang, DDS, MS, PhD
Abstract
This article will describe requirements for case selection
and review the procedures for apexogenesis and apexification in immature permanent teeth. Nonclinical and
clinical data will be presented to support the recommendations, and outcomes will be presented from clinical
studies. The dental pulp is an ectomesenchymally
derived connective tissue with certain unique properties
such as being encased in hard tissues, which limits its
collateral circulation. The pulp provides a matrix for
binding of its cells and provides support allowing
communication between the cells. In addition to
immune cells, the dental pulp contains odontoblasts,
which are specialized cells capable of producing dentin.
In the absence of a vital pulp, dentin deposition is
arrested. When an immature tooth is affected by caries
or trauma, the pulp requires proper management
according to the degree of inflammation and its vitality.
Maintenance of pulp vitality will allow continued root
development along the entire root length. If the pulp
is irreversibly inflamed or necrotic, root-end closure
procedures are required when the apex has not fully
formed. (J Endod 2013;39:S26S29)

Key Words
Apexification, apexogenesis, immature permanent
teeth, treatment

From the Department of Endodontics, Loma Linda University, Loma Linda, California.
This article is being published concurrently in Pediatric
Dentistry 2013;35(2). The articles are identical. Either citation
can be used when citing this article.
Address requests for reprints to Dr Shahrokh Shabahang, 5
East Citrus Avenue, Suite 201, Redlands, CA 92373. E-mail
address: shahrokh@shabahang.net
0099-2399/$ - see front matter
Copyright 2013 American Academy of Pediatric Dentistry
and American Association of Endodontists.
http://dx.doi.org/10.1016/j.joen.2012.11.046

S26

Shabahang

Role of the Dental Pulp in Tooth Development

he dental pulp contains immune cells that allow it to mount a response against offending irritants. The pulp also contains odontoblasts, which are specialized to form
dentin. In the absence of a vital pulp, the tooth structure is susceptible to infection, and
dentin deposition is arrested. Maintenance of pulp vitality is imperative in an immature
permanent tooth to allow continued root development. The pulp tissue is removed when
pathologically inflamed or necrotic.
Although studies are underway to develop materials and techniques for pulp
regeneration procedures, the purpose of this review is to provide an overview of apexogenesis and apexification in immature permanent teeth with pulpal pathosis.

Apexogenesis or Apexication
Proper assessment of the affected tooth is critical in determining an accurate diagnosis and prescribing the appropriate treatment plan. Assessment of pulp vitality will aid
in determining the proper treatment option. If vital and not irreversibly inflamed, maintenance of its vitality will allow natural continued root development. Figure 1 presents
a flow chart to facilitate the decision-making process when treating permanent teeth
with incomplete root development.
Assessment of the tooth in question is made by using radiographic evaluation to
determine the maturity of the developing root and clinical evaluation that is based on
history and clinical testing. Obviously immature teeth are frequently associated with
child patients. Pulp testing in children is a complex procedure and subjective in nature.
Maintenance of pulp vitality by using apexogenesis will allow continued root development along the entire root length. Depending on the extent of inflammation, pulp
capping, shallow pulpotomy, or conventional pulpotomy may be indicated. The dental
pulp in young patients is more cellular and able to recover from injuries. Cvek et al (1)
demonstrated that in teeth with complex crown fractures, the exposed pulp maintained
its vitality for up to 7 days. In these teeth, only the most superficial 2 mm of the pulp is
inflamed and requires removal.
If pulpal necrosis occurs in immature teeth, an alternative treatment approach
must be used because of the presence of an open apex (2). The young pulpless tooth
frequently has thin, fragile walls, which makes it difficult to adequately clean and to
obtain the necessary apical seal (2). Traditionally, the approach has been to use
calcium hydroxide (CH) to induce apexification after disinfection of the root canals
in the conventional manner (3). Completion of endodontic therapy was typically delayed until completion of root-end closure through apexification. Apexification is
defined as a method of inducing a calcified barrier in a root with an open apex or
the continued apical development of an incompletely formed root in teeth with necrotic
pulp (4).
The disadvantages of traditional, long-term CH therapy include variability in
treatment time, unpredictability of formation of an apical seal, difficulty in
following up patients, and delayed treatment. An alternative to CH therapy is
placement of an apical plug. Several investigators have demonstrated the
use of dentin apical plugs in nonsurgical root canal therapy of mature teeth
(59). Mineral trioxide aggregate (MTA) is a material that may be best suited
as an apical plug. In 1999, Shabahang et al (10) showed consistent barrier
formation when MTA was used as an apical plug in an in vivo dog model
with open apices. Several studies have confirmed successful clinical outcomes
including healing of existing periapical lesions in majority of immature teeth
that were treated with an MTA apical plug (11, 12).

JOE Volume 39, Number 3S, March 2013

Injuries to Permanent Dentition Symposium

used root canal irrigants (26, 27). MTAD is effective as a final
rinse before obturation to disinfect the root canal system and to
remove the smear layer. In 2001, Iwaya et al (28) published
a case that demonstrated the effectiveness of a double antibiotic
paste to disinfect a premolar with a necrotic pulp and a large periradicular radiolucent lesion. Three years later, Banchs and Trope
(29) published a similar case. In this case report and subsequent
studies, Tropes group recommended a mixture of metronidazole,
ciprofloxacin, and minocycline. In in vitro studies this antibiotic
combination has demonstrated the potential to disinfect the root
canal system (30).

Treatment Outcomes
Figure 1. Case selection for treatment of permanent teeth with incomplete
root development.

The advantages of using an apical plug include requirement for

fewer appointments to complete the treatment, more predictable
apical barrier formation, and reduced need for patient follow-up
appointments. The disadvantage of this technique is that, similarly to
CH therapy, it only addresses the apical opening and does not account
for complete root development along the entire root length. Regardless of the technique used, a critical step in treatment of pulpless teeth
with open apices is proper d
ebridement and disinfection of the canal
space.

Disinfection Protocols
Immature permanent teeth pose special challenges during
endodontic procedures not only because of the wide-open root apex
but also because of the thin dentin walls. Therefore, d
ebridement is
completed primarily by chemical means to remove any remaining
pulp tissues and for disinfection. Furthermore, an accurate determination of root length is required to ensure complete canal d
ebridement
and to confine treatment materials to the canal space to avoid damaging
the very valuable remnants of the Hertwig epithelial root sheath. Generally, electronic apex locators are not accurate in teeth with wide-open
apices (13). Radiographic root determination is the best means to
obtain accurate root length measurement.
Sodium hypochlorite (NaOCl) and CH have excellent tissuedissolving properties as well as antimicrobial efficacy (1418).
Whereas NaOCl exerts its effect during the course of the procedure,
CH requires additional exposure time. A 1-week obturation of the
canal space with CH will allow disinfection along with dissolution and
removal of pulpal remnants (19). Despite its convenient availability,
several investigators have reported shortcomings with respect to
NaOCls ability to completely disinfect the root canal space (2022).
Long-term exposure to CH may also have detrimental effects on
dentin. Studies have shown that long-term CH therapy that would expose
root dentin to CH for periods exceeding 1 month results in structural
changes in the dentin, with higher susceptibility to root fracture
(23, 24).
Use of antibiotics has also been documented during the past
years and is regaining popularity in recent years. In 1980, Das
(25) reported successful apexification of a tooth after root canal
debridement and intracanal antibiotic therapy with an oxytetracycline
HCl ointment. In 2003, Torabinejad and his group published a series
of reports to demonstrate the advantages of a mixture of doxycycline, citric acid, and detergent (BioPure MTAD; DENTSPLY Tulsa
Dental Specialties, Tulsa, OK) over NaOCl and other commonly
JOE Volume 39, Number 3S, March 2013

Nonclinical and clinical studies have reported good results with

a variety of techniques. The most significant shortcoming of longterm CH therapy is the length of time required to complete treatment
and frequent challenges in following up with patients over time. A
root fracture at the cervical region is a common cause of failure
in these cases. Thin dentin at the cervical region and changes in
the dentin structure resulting from long exposure times to CH are
the causative factors. Table 1 summarizes the outcome results
from several studies.
Depending on the study, the speed of barrier formation by using
CH therapy varies from 3 to 24 months (2, 31). The suggested time
to change the CH in the canal varies from once every 3 months, once
every 68 months, or not at all (3133).
Torneck and Smith (34) have indicated that there may be
incomplete bridging of the apex, even though a two-dimensional
radiograph may give the appearance of complete bridge formation.
Periradicular inflammation may persist around the apices of many
teeth because of the presence of necrotic tissue in the irregularities
of the apical bridge. Therefore, the presence of a radiographically
and clinically closed apex is not necessarily indicative of a normal
periodontium (35).
Another major drawback of the apexification protocol that uses CH
is the effect that a long-term application of CH has on the structural
integrity of the root dentin. Several studies have demonstrated that
with longer exposures of dentin to CH, its ability to resist fracture is
significantly decreased (23, 36).
In a systematic review and meta-analysis comparing the
outcomes of CH apexification and MTA apical plug, the authors
concluded that the clinical success of both procedures was the
same (37). On the basis of the combined data of the 2 studies,
the difference in clinical success between the 2 treatment regimens
was not statistically significant.
Overall, the results of several studies show that MTA plugs are
effective in treating immature permanent teeth with necrotic pulps.
The advantages of apexification that uses an MTA plug are reduced treatment time and a more predictable barrier formation. The shortcoming,
similar to CH therapy, is that placement of an apical plug does not
account for continued root development along the entire root length.
Complete root development requires a viable pulp containing cells
that can differentiate into dentin-producing odontoblasts. For this,
ongoing studies are aiming to identify procedures and materials that
allow pulp regeneration. The dental pulp is complex with a variety of
cells, nerves, and blood vessels. To regenerate this organelle, it is
important to keep in mind the required prerequisites, including cells
that are capable of differentiating into pulp cells, the proper signal
that is required for the differentiation, and an appropriate scaffold
that is suitable for guiding regeneration of the desired tissues, while
keeping out the faster growing osseous tissues.

Apexogenesis and Apexification

S27

Shabahang

Technique/material

Investigator(s)

No. of cases

Observation

JOE Volume 39, Number 3S, March 2013

CH therapy
CH therapy
CH therapy

Heithersay, 1970
Ghose et al, 1987
Morfis and Siskos, 1991

21
43
34

1475 months
310 months

CH therapy
CH therapy

Lee et al, 2010

Walia et al, 2000

32
15

1014 weeks

CH therapy

Dominguez Reyes et al, 2005

26

Average time 12.19 months

CH therapy

Mendoza et al, 2010

28

Comparison of MTA plug

with CH therapy
Comparison of MTA plug
with CH therapy

El-Meligy and Avery, 2006

15

3.2413.96 months (mean

8.6 months)
12 months

Pradhan et al, 2006

20

8 months

MTA plug

Pace et al, 2007

11

2 years

MTA plug
MTA plug
MTA plug
MTA plug
MTA plug
MTA plug

Erdem and Sepet, 2008

Sarris et al, 2008
Holden et al, 2008
Nayar et al, 2009
Annamalai and Mungara, 2010
Moore et al, 2011

5
17
20
38
30
22

MTA plug
MTA plug

Simon et al, 2007

Witherspoon et al, 2008

43
78

2 years
11.7 years
1244 months
12 months
12 months
Mean follow-up time
23.4 months
12 months
Mean recall time was
19.4 months

A PubMed search was conducted in August 2012 to identify citations with CH, MTA, apical plug, outcomes, and clinical studies.

Outcomes
Apical canal seen radiographically, but no apical barrier clinically
49 of 51 developed an apical barrier
Continued root development in 6 cases, continued root development
and bridge formation in 3 cases, bridge formation in 21 cases, and
in 4 cases no root-end closure
Apical closure in necrotic cases with or without lesion
100% apical closure with porous barrier. Older children with narrow
apex had shorter time; teeth without periapical infection showed
faster results.
Apical closure obtained in 100% of cases; 88.4% needed 34 sessions
(average of 3.23 sessions)
Cementoid tissue (85.72%) or osseous tissue (14.28%)
2 of CH teeth had become reinfected, but all teeth treated with MTA
plug remained successful
Periapical lesions resolved in 4.6  1.5 months for MTA group
and in 4.4  1.3 months for CH group. Total treatment was
completed in 0.75  0.5 months for MTA group and 7  2.5 months
for CH group.
10 of 11 cases healed, and remaining case considered incomplete
healing
4 of 5 teeth healed; 1 case in MTA was extruded
94.1% clinical success, 76.5% radiographic success; 17.6% uncertain
Healing rate was 93.75%
All teeth were clinically and radiographically successful
100% success clinically and radiographically
Clinical and radiographic success rate of 95.5%; discoloration in
22.7% of teeth
81% healed
93.5% of teeth treated in 1 visit healed, and 90.5% of teeth treated in
2 visits healed

Injuries to Permanent Dentition Symposium

S28
TABLE 1. Outcomes of Clinical Studies with CH Therapy and MTA Apical Plug

Injuries to Permanent Dentition Symposium

Acknowledgments
The author denies any conflicts of interest related to this study.

References
1. Cvek M, Cleaton-Jones PE, Austin JC, Andreasen JO. Pulp reactions to exposure after
experimental crown fractures or grinding in adult monkeys. J Endod 1982;8:3917.
2. Frank AL. Therapy for the divergent pulpless tooth by continued apical formation.
J Am Dent Assoc 1966;72:8793.
3. Seltzer S. The root apex. In: Seltzer S, Krasner P, eds. Endodontology: Biologic
Considerations in Endodontic Procedures. Malvern, PA: Lea & Febiger; 1988:130.
4. Sheely 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:
2416.
5. Tronstad L. Tissue reactions following apical plugging of the root canal with dentin
chips in monkey teeth subjected to pulpectomy. Oral Surg Oral Med Oral Pathol
1978;45:297304.
6. Holland R, De Souza V, Nery MJ, et al. Tissue reactions following apical plugging of
the root canal with infected dentin chips: a histologic study in dogs teeth. Oral Surg
Oral Med Oral Pathol 1980;49:3669.
7. Holland R, Nery MJ, Souza V, et al. The effect of the filling material in the tissue reactions following apical plugging of the root canal with dentin chips: a histologic study
in monkeys teeth. Oral Surg Oral Med Oral Pathol 1983;55:398401.
8. Holland GR. Periapical response to apical plugs of dentin and calcium hydroxide in
ferret canines. J Endod 1984;10:714.
9. Brady JE, Himel VT, Weir JC. Periapical response to an apical plug of dentin filings
intentionally placed after root canal overinstrumentation. J Endod 1985;11:3239.
10. Shabahang S, Torabinejad M, Boyne PJ, et al. A. comparative study of root-end
induction using osteogenic protein-1, calcium hydroxide, and mineral trioxide
aggregate in dogs. J Endod 1999;24:15.
11. Holden DT, Schwartz SA, Kirkpatrick TC, Schindler WG. Clinical outcomes of artificial root-end barriers with mineral trioxide aggregate in teeth with immature apices.
J Endod 2008;34:8127.
12. Moore A, Howley MF, OConnell AC. Treatment of open apex teeth using two types of
white mineral trioxide aggregate after initial dressing with calcium hydroxide in children. Dent Traumatol 2011;27:16673.
13. Hulsmann M, Pieper K. Use of an electronic apex locator in the treatment of teeth
with incomplete root formation. Endod Dent Traumatol 1989;5:23841.
14. Th
e SD. The solvent action of sodium hypochlorite on fixed and unfixed necrotic
tissue. Oral Surg Oral Med Oral Pathol 1979;47:55861.
15. Cunningham WT, Balekjian AY. Effect of temperature on collagen-dissolving ability
of sodium hypochlorite endodontic irrigant. Oral Surg Oral Med Oral Pathol 1980;
49:1757.
16. Cunningham WT, Joseph SW. Effect of temperature on the bactericidal action of
sodium hypochlorite endodontic irrigant. Oral Surg Oral Med Oral Pathol 1980;
50:56971.
17. Morgan RW, Carnes DL Jr, Montgomery S. The solvent effects of calcium hydroxide
irrigating solution on bovine pulp tissue. J Endod 1991;17:1658.

JOE Volume 39, Number 3S, March 2013

18. Baumgartner JC, Cuenin PR. Efficacy of several concentrations of sodium hypochlorite for root canal irrigation. J Endod 1992;18:60512.
19. Sjogren U, Figdor D, Sp
angberg L, Sundqvist G. The antimicrobial effect of calcium
hydroxide as a short-term intracanal dressing. Int Endod J 1991;24:11925.
20. Shabahang S, Pouresmail M, Torabinejad M. In vitro antimicrobial efficacy of MTAD
and sodium hypochlorite. J Endod 2003;29:4502.
21. Waltimo T, Trope M, Haapasalo M, rstavik D. Clinical efficacy of treatment procedures in endodontic infection control and one year follow-up of periapical healing.
J Endod 2005;31:8636.
22. Siqueira JF Jr, Rocas IN. Clinical implications and microbiology of bacterial persistence after treatment procedures. J Endod 2008;34:1291301.
23. Andreasen JO, Farik B, Munksgaard EC. Long-term calcium hydroxide as a root
canal dressing may increase risk of root fracture. Dent Traumatol 2002;18:
1347.
24. Hatibovi
c-Kofman S, Raimundo L, Zheng L. Fracture resistance and histological findings of immature teeth treated with mineral trioxide aggregate. Dent Traumatol
2008;24:2726.
25. Das S. Apexification in a nonvital tooth by control of infection. J Am Dent Assoc
1980;100:8801.
26. Torabinejad M, Khademi AA, Babagoli J, et al. A new solution for the removal of the
smear layer. J Endod 2003;29:1705.
27. Torabinejad M, Shabahang S, Aprecio R, Kettering JD. The antimicrobial effect of
MTAD: an in vitro investigation. J Endod 2003;29:4003.
28. Iwaya SI, Ikawa M, Kubota M. Revascularization of an immature permanent tooth
with apical periodontitis and sinus tract. Dent Traumatol 2001;17:1857.
29. Banchs F, Trope M. Revascularization of immature permanent teeth with apical periodontitis: new treatment protocol? J Endod 2004;30:196200.
30. Hoshino E, Kurihara-Ando N, Sato I. In-vitro antibacterial susceptibility of bacteria
taken from infected root dentine to a mixture of ciprofloxacin, metronidazole and
minocycline. Int Endod J 1996;29:12530.
31. Finucane D, Kinirons MJ. Non-vital immature permanent incisors: factors that may
influence treatment outcome. Endod Dental Traumatol 1999;15:2737.
32. Chosack A, Sela J, Cleaton-Jones P. A histological and quantitative histomorphometric study of apexification of nonvital permanent incisors of vervet monkeys
after repeated root filling with a calcium hydroxide paste. Endod Dent Traumatol 1997;13:2117.
33. Abbott PV. Apexification with calcium hydroxide: when should the dressing
be changed? the case for regular dressing changes. Aust Endod J 1998;24:
2732.
34. Torneck CD, Smith J. Biologic effects of endodontic procedures on developing
incisor teeth: Ieffect of partial and total pulp removal. Oral Surg Oral Med
Oral Pathol 1970;30:25866.
35. Koenigs JF, Heller AL, Brilliant JD, et al. Induced apical closure of permanent teeth in
adult primates using a resorbable form of tricalcium phosphate ceramic. J Endod
1975;1:1026.
36. Rosenberg B, Murray PE, Namerow K. The effect of calcium hydroxide root filling on
dentin fracture strength. Dent Traumatol 2007;23:269.
37. 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:e3642.

Apexogenesis and Apexification

S29