13652591, 0, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/iej.13809 by CAPES, Wiley Online Library on [12/02/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.

com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
Received: 20 June 2022
| Accepted: 28 July 2022

DOI: 10.1111/iej.13809

REVIEW ARTICLE

Review of guidance for the selection of regenerative

endodontics, apexogenesis, apexification, pulpotomy, and
other endodontic treatments for immature permanent
teeth

Peter E. Murray

Private Consultant, Fort Lauderdale, Abstract

Florida, USA
This review guidance is a work in progress because the limitations of regenerative
Correspondence endodontics are still being discovered. The endodontic treatments for immature per-
Peter E. Murray, Private Consultant, manent teeth with a necrotic pulp can vary considerably among endodontic practi-
Fort Lauderdale, FL, USA.
Email: p_e_murray@outlook.com
tioners. Whereas, regenerative endodontic treatments are growing in popularity and
are creating ever more complex treatment protocols, involving revascularization and/
or autologous platelet-­rich plasma and scaffolds to elicit host stem cell de novo tissue
formation to reestablish the vitality of immature teeth for the purpose of continuing
root maturation. Despite much evolving controversy about their potential benefits,
risks, prognosis, and contraindications, this review is aimed to discuss how to ensure
that regenerative endodontic treatments are successful, by strictly adhering to case
selection criteria, and following precise steps to accomplish and monitor the suc-
cess of the treatment. A review of the endodontic literature was performed, together
with practical observations of the problems and outcomes of performing regenera-
tive endodontic treatments. Traditionally, apexification has long been the treatment
of choice provided to immature teeth with a necrotic pulp. Regenerative endodontics
may be provided as an alternative to apexification, if the tooth and patient meet all
the case selection criteria, and if there are no contraindications. Regenerative endo-
dontics has the unique potential advantage of being able to continue the root devel-
opment in immature permanent teeth, thereby potentially saving the teeth for the
lifetime of the patient. Whereas, conventional endodontic root canal treatment, Cvek
partial pulpotomy, apexogenesis, and apexification, should always be provided when
these treatments are more likely to benefit the patient because they can be more suc-
cessful than regenerative endodontics.

KEYWORDS
apexification, apexogenesis, endodontology, pulpotomy, regenerative endodontics, review

© 2022 British Endodontic Society. Published by John Wiley & Sons Ltd

Int Endod J. 2022;00:1–12.  wileyonlinelibrary.com/journal/iej | 1

 |

13652591, 0, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/iej.13809 by CAPES, Wiley Online Library on [12/02/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
2    REGENERATIVE ENDODONTICS

I N T RO DU CT ION from a long-­term success rate of over 86% (Elemam &

Pretty, 2011). Nevertheless the opposite, a lack of suc-
Millions of young patients have their immature per- cess, can be true for immature permanent teeth following
manent teeth extracted every year, although most treatment. This is because of their fragile root physiology
endodontists and paediatric dentists have personalized re- and anatomy, which creates more complex diagnostic and
generative endodontic treatment strategies that are avail- clinical challenges (Harlamb, 2016). Fragile immature
able to do almost everything possible to save these teeth teeth can have dentinal walls which are thin and weak,
(Murray et al., 2007). Regrettably, due to toothache, most making them prone to a stress-­overload fracture (Lawley
patients opt to have a painful tooth extracted (Silva-­Junior et al., 2004). Thus, the success of regenerative endodontic
et al., 2017). Some patients do not apprehend the ability treatment to save fragile immature teeth with a necrotic
of endodontic treatments to alleviate the toothache, and pulp can be dependent on the endodontists ability to ad-
save their natural teeth, which is preferable over the long equately disinfect the root canals. In addition to bringing
term to maintain their quality of life and ability to chew about the regeneration of replacement de novo pulp-­like
food (Hugo et al., 2009). There is no dispute that dental tissue by revascularization through the root apex, to revi-
implants, bridges, and dentures can be aesthetically and talize the tooth for it to continue the mineralization and
functionally valuable to replace missing teeth. But dental maturation of the root dentinal walls to strengthen the
implants are a potential source of dental pain, discomfort, tooth root. Thereby making the root stronger to save the
lack of tooth sensation, need for invasive bone surgeries, tooth by making it more resistant to a fracture.
bleeding and peri-­implantitis infection problems, risk of Some endodontists may lack the training and experi-
failures (Clark & Levin, 2019), and chewing limitations ence to provide regenerative endodontic treatments. This
for patients, in addition to the risk of healing complica- is because some endodontists who were surveyed admit-
tions following tooth extractions (Lodi et al., 2021) can- ted they lack a sound knowledge of regenerative endodon-
not be overlooked because of the dentist's responsibility tics, and only one in five, had a positive perception of its
to provide treatments to patients based on an unbiased usefulness (Mayya et al., 2021). Hence the need for this
evidence base (Clark & Levin, 2019). Greater advocacy review, not only to focus on regenerative endodontics, but
by endodontists and dental associations of their skills to also to provide guidance on patient selection, case selec-
save natural teeth, is needed to improve the uptake of end- tion, and the status of root development, to guide the en-
odontic treatments, to help counter the increasing trend dodontist to use differential diagnosis criteria to select the
towards teeth extraction, and the placement of expensive most appropriate type of endodontic treatment plan for
dental implants (Clark & Levin, 2019). Endodontic treat- every type of immature tooth. The endodontic treatment
ments can be as successful as dental implants. Especially options for immature permanent teeth, include regener-
when treatment planning uses a differential diagnosis of ative endodontics, conventional non-­surgical endodontic
the health status of the patient, the status of root devel- root canal treatment, Cvek partial pulpotomy, apexogene-
opment, and the pulp status of the immature tooth, to sis, and apexification.
determine which endodontic treatments are appropriate A recent survey has shown that most endodontists
or inappropriate. Ultimately, the selection of the most ap- are willing to obtain training to provide regenerative
propriate treatment plan is the one key factor that is most endodontics to patients (Mayya et al., 2021). However,
likely to benefit the patient by providing them with the placing the focus solely on regenerative endodontics
highest quality longest lasting endodontic care. as a gold standard can be a risky educational strategy.
This is because it may lead some endodontists to in-
correctly presuppose that because a tooth is immature,
E N D O DO NT IC T R E AT M E N T that regenerative endodontics must always be the cor-
TO SAV E T R AU M AT IZ E D AN D rect and most beneficial treatment of choice for the
DI S E A S E D I MMAT U R E T E ET H patient's tooth. Regenerative endodontics is not always
the best choice among all of the available endodontic
Traumatic dental injuries occur frequently in children treatments for traumatized or caries-­affected immature
and young adults, 25% of school children and 33% of teeth. This is because the clinical failure rates of regen-
adults have experienced trauma to the permanent denti- erative endodontics to revitalize immature teeth can be
tion, with most of the injuries occurring before 19 years as high as 40% (Murray, 2018; Wikström et al., 2022).
of age (Levin et al., 2020). Adult patients who have con- Post-­treatment painful and/or severe swelling flare ups
ventional root canal treatments to save fully mature per- can be observed in one-­third of cases, and in almost half
manent teeth with an irreversibly injured pulp, diseased of cases, there was no apparent root development and
necrotic pulp, or accidentally exposed pulp, can benefit apical closure (Meschi et al., 2021). In contrast, some
 |

13652591, 0, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/iej.13809 by CAPES, Wiley Online Library on [12/02/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
MURRAY    3

clinical trials report tooth survival rates above 93% tissues; thus, the prognosis is that the pulp will become
(Elfrink et al., 2021), and overall success rates above necrotic (Ricucci et al., 2014).
80% for regenerative endodontic treatments (Chrepa Necrotic dental pulp—­Death of the cells of the dental
et al., 2020). Not all the failures of regenerative endodon- pulp (Yu & Abbott, 2007).
tic treatments are the fault of the provider endodontist, Pulp revascularization/revitalization—­A necrotic
but the large variations in the reports of success and fail- pulp and irreversible pulpitis procedure which disin-
ure rates, suggest that precise case selection criteria to- fects the root canal with antibiotics or/and antimicro-
gether with precise adherence to the steps to accomplish bial agents. The periapical tissues are instrumented
regenerative endodontics can be extremely important through the open root apical foramen to cause bleeding
for the success of the treatments (AAE, 2016). into the canal to revascularize it. Thereby, promoting
tissue formation within the root canal for the contin-
ued deposition of mineral to strengthen dentine and
E N D O DO NT IC T E R MIN OLOGY FOR grow the roots of immature teeth (do Couto et al., 2021;
T R E AT M E NT S FOR IMMAT U R E Namour & Theys, 2014; Wigler et al., 2013; Wikström
T E ET H et al., 2022).
Regenerative endodontics—­A necrotic pulp and irre-
It is essential that the endodontic treatment terminologies versible pulpitis procedure which debrides tissues from
are defined to be able to communicate with colleagues the root canal, disinfects the root canal, instruments the
using the same language. Unfortunately, the definitions periapical tissues through the open root apical foramen
can change slightly over time, as also usage between dif- to cause bleeding into the canal to revascularize it, as de-
ferent authors, dental dictionaries, and professional as- scribed above. In addition to adding a scaffold or biological
sociations. However, mostly the key elements of the procedure within the root canal to promote vital tissue for-
endodontic treatment definitions for immature teeth are mation which will continue the deposition of mineral to
similar, as summarized here. strengthen dentine and grow the roots of immature teeth
Some key terminologies for the endodontic treatments (Chrepa et al., 2020; Elfrink et al., 2021; He et al., 2017;
for immature teeth are: Meschi et al., 2021; Murray, 2018; Murray et al., 2007;
Apexification—­A necrotic pulp and irreversible pulpi- Trope, 2008). The steps to accomplish regenerative end-
tis procedure which debrides, disinfects, and obturates the odontics are shown in Table 1.
root canal of immature teeth. The obturation of the root
canal with calcium hydroxide or mineral trioxide aggre-
gate (MTA) will induce an apical calcified barrier to help AN OV ERV IEW OF THE CASE
save the tooth (Goldstein et al., 1999; Rafter, 2005; Shaik SELECTION CRITERIA FOR
et al., 2021). REGENERATIV E ENDODONTICS
Apexogenesis—­A vital pulp procedure which debrides
the coronal injured pulp from the root canal of an im- The success of regenerative endodontic treatments also in-
mature permanent tooth. The removal of the superficial cluding pulp revascularization and revitalization, can vary
injured pulp will allow the remaining vital pulp to con- widely, with a success rate of 60% (Wikström et al., 2022).
tinue the maturation and physiological development of This suggests the need to adhere to strict case selection
the roots (Goldstein et al., 1999; Mousivand et al., 2021). criteria to ensure the optimal success of regenerative en-
Conventional non-­ surgical root canal treatment—­A dodontic procedures can be accomplished. The case selec-
necrotic pulp and irreversible pulpitis procedure for ma- tion criteria may include.
ture teeth which uses instruments, irrigants, and chelat-
ing agents to debride infected tissues and disinfects the
root canal by cleaning, shaping, sealing, and obturation Patients aged 6 to 17 years
(Metzger et al., 2010; Peters, 2004).
Cvek partial pulpotomy—­A vital pulp procedure which Regenerative endodontic treatments are not recom-
debrides 2 mm of coronal injured pulp from a root canal. mended to be provided to deciduous (baby) teeth, due to
The removal of the superficial injured pulp will allow the the risk of retaining these teeth, and interfering with the
remaining vital pulp to continue the maturation and phys- eruption pattern of the permanent teeth. The youngest age
iological development of the roots (Mejàre & Cvek, 1993; that permanent teeth erupt is 6 years of age (Almonaitiene
Sari, 2002). et al., 2012), thus because regenerative endodontics should
Irreversible pulpitis—­ Chronic inflammation of the only be provided to permanent teeth, the minimum age of
dental pulp which cannot be reversed to heal the damaged patients is 6 years of age.
 |

13652591, 0, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/iej.13809 by CAPES, Wiley Online Library on [12/02/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
4    REGENERATIVE ENDODONTICS

TABLE 1 Steps to accomplish regenerative endodontics TABLE 1 (Continued)

Patient care and consent Restore tooth with composite resin permanent restoration and
Ensure the patient satisfies the case section criteria for check occlusion
regenerative endodontics (Figure 1) and obtain patient Monitoring healing and recall of patient
approval, and parent and guardian consent for the treatment Monitor tooth for flare ups and periapical tissues for healing
plan and provide a retreatment if necessary
Tooth selection for regenerative endodontics Recall patient every 6 months to check tooth for vitality and root
The tooth must be permanent and very immature with a wide-­ development
open apical foramen wider than 1.1 mm and have an injured
or exposed pulp. The tooth must have thin walls that will
benefit from a continued development of the root, so that it
can become stronger and less prone to failure in later life
Regenerative endodontics have been provided to ma-
ture adult teeth in patients aged older than 17 years of age
Anaesthesia of the immature permanent tooth
(He et al., 2017). However, when adult teeth have thick
Establish an anaesthetic block of the tooth using 3%
dentinal walls to withstand fracture, providing regen-
Mepivacaine, without vasoconstrictors, one carpule will be
needed every 20 min
erative endodontics does not provide the adult patient
with any reasonable potential benefits. This is because of
Disinfection, irrigation, and instrumentation of the tissues within
root canals
the greater risk of failure, greater risk of complications,
greater risk of a painful flareup, and greater risk that a re-
Isolate the tooth with a rubber dam and cut a root canal access
wide enough to see all the walls
treatment will be necessary, due to the success rate being
60% (Murray, 2018; Wikström et al., 2022). In addition to
Irrigate the root canal with 20 ml of 1.25% NaOCl with suction
to prevent leakage
the regenerative potential of adult mature teeth, being ex-
tremely limited (Trope, 2008), suggesting the ability for
Establish the root canal working length with a hand file and
radiograph
oral tissue regeneration decreases with patient age and
maturity. Conventional non-­surgical root canal treatment
Introduce a hand or rotary file into the root canal and avoid
instrumenting the dentinal walls
is the optimum treatment for mature adult permanent
teeth, because of the greater long-­term success rate of over
Pack the root canals with calcium hydroxide or a triple
antibiotic paste of Ciprofloxacin, Metronidazole,
86% over 10 years (Elemam & Pretty, 2011) and lowest risk
Minocycline to a final concentration of 0.1 mg/ml, for up to of complications, such as recurrent pain.
4 weeks and restore the tooth with a temporary restoration
Irrigation, chelation, rinsing and drying root canals
Irrigate the root canal with 20 ml of 1.25% NaOCl with suction
Obtain a medical clearance for patients
to prevent leakage with compromised healing
Rinse the root canals with a chelating agent of 17% EDTA or
Qmiz2in1 for 60 s Successful regenerative endodontic treatment requires
Final rinse of root canal with sterile saline
revascularization, which is the formation of a blood clot
within the tooth (do Couto et al., 2021). Patients who suf-
Dry root canal with paper points
fer from any systemic disease such as haemophilia, and von
Revascularization and scaffolds inside root canals
Willebrand disease which can compromise blood clotting, or
Stir periapical tissue with a bent k-­file 3 mm through the root who take blood thinner medicaments (anticoagulants) are
apex to induce bleeding
at a greater risk of uncontrolled bleeding (Weibert, 1992).
If you wish to use a BCR approach, wait for blood to fill the root
Thus, it is not recommended to provoke uncontrolled bleed-
canals up to the level of the cementoenamel junction. If you
ing in these patients, due to the risk of tissue damage and
wish to attempt to use PRP or PRF to revascularize the root
canal, you should allow an extra 30 min to use phlebotomy suffering due to blood loss. Furthermore, because regenera-
to obtain the patient's own blood from a vein in their arm, tive endodontics also requires healing and dental pulp-­like
and to centrifuge it using a PRP or PRF kit before placing the tissue formation (Trope, 2008), where a patient suffers from
PRP or PRF into the root canal a systemic disease which inhibits healing, the treatment is
Insert bioabsorbable collagen scaffolds using forceps' to more likely to fail and be compromised. When any doubt
lightly pack the root canal space from the apex to the exists about a patient's compromised health status, medi-
cementoenamel junction cations, and suitability for regenerative endodontics, it is
Restore tooth best practice to obtain a medical clearance from the pa-
Seal root canal orifice with a 2 mm thick layer of white MTA tients' other healthcare providers to prove that the patient
placed in contact with the scaffolds is healthy enough for treatment. If the patient's health sta-
tus suggests that regenerative endodontics will have a poor
 |

13652591, 0, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/iej.13809 by CAPES, Wiley Online Library on [12/02/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
MURRAY    5

F I G U R E 1 Case selection criteria to

attempt regenerative endodontics

prognosis for an immature permanent tooth with a necrotic treated, and sealed to create a long-­lasting hermetic bar-
pulp, then apexification can be provided as necessary. rier prior to regenerative endodontics, to prevent the mi-
croleakage of microorganisms into the root canal. This is
because a failure to prevent microleakage and a failure to
Compliant patient adequately disinfect the root canal will compromise heal-
ing and is likely to fail (Wikström et al., 2022). It is pos-
As few as 39.5% of paediatric patients are compliant with sible to provide a regenerative endodontic retreatment if
dental clinical follow-­up visits (Gune & Katre, 2021). There any of these complications occur after the initial treat-
is the potential for some patients who have begun multiple ment, however it must be recognized that the outcomes
visit regenerative endodontic treatments, to cease attend- may be unpredictable (Mohammadi et al., 2021). The size
ing visits to complete the final steps in the treatment plan, of periapical lesions may be reduced following regenera-
likely because the toothache was alleviated. Consequently, tive endodontic treatment, but the periapical tissues are
some patients have antibiotic paste in the root canals of unlikely to be completely healed (Kandemir Demirci
their teeth to disinfect the root canals, without any obtura- et al., 2020).
tion of the root canals and without a final restoration of the
tooth to finish the course of treatment. In this incomplete
treatment state, the tooth has a poor prognosis because it Immature permanent tooth with thin
will not be able to regenerate, and still may have a linger- dentinal walls
ing infection and necrotic pulp. To avoid the problem of
patients failing to complete a course of regenerative endo- The most fragile immature permanent teeth in the young-
dontics, multiple visit treatments should only be provided est patients aged 6–­9 years with thin dentinal walls are
to children who have a history of attending dental visits. If the most likely to benefit from regenerative endodontic
there is doubt about a patient's ability to comply with mul- treatment (Wikström et al., 2022) because it can continue
tiple treatment visit requirements, the endodontic treat- root development by thickening the dentinal walls, and
ment should be provided in a single visit, to ensure it can thereby strengthen the teeth to withstand a stress over-
be completed. load fracture (Lawley et al., 2004). Consequently, there
is no obvious benefit to providing regenerative endodon-
tic treatment to teeth which already have thick enough
Treated swelling, sinus track, and dentinal walls to withstand a fracture. Thus, if the pulp
visible lesions is necrotic or has irreversible pulpitis likely to become
necrotic, with thick dentinal walls, the most optimum
Where a patient has swelling, visible lesions, defects and treatment will be apexification (Goldstein et al., 1999;
sinus tracks associated with the root canal of an immature Rafter, 2005; Shaik et al., 2021), rather than regenerative
tooth, these must first be resolved, drained, disinfected, endodontics.
 |

13652591, 0, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/iej.13809 by CAPES, Wiley Online Library on [12/02/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
6    REGENERATIVE ENDODONTICS

Dental pulp is necrotic or has bleeding (Wikström et al., 2022), which can also be stated
irreversible pulpitis as a failure to accomplish adequate root canal revasculari-
zation. The flow of blood from the periapical tissues into
The goal of regenerative endodontic treatment is to de- the root canal, and to fill the root canal space is essential
bride necrotic and infected tissues from the root canal, for revascularization (do Couto et al., 2021; Namour &
disinfect the root canal, and to instrument the periapi- Theys, 2014; Wigler et al., 2013; Wikström et al., 2022).
cal tissues through the open root apical foramen to cause This is because without an adequate supply of blood there
bleeding into the canal to revascularize it. Then, adding a can be no revascularization and no de novo replacement
scaffold or biological procedure within the root canal to pulp-­like tissue formation to revitalize an immature tooth,
promote vital tissue formation which will continue the and to mineralize the dentinal walls and continue root
deposition of mineral to strengthen dentine and grow the development.
roots of immature teeth (Namour & Theys, 2014; Wigler A closed apical foramen in mature teeth, provides
et al., 2013; Wikström et al., 2022). Therefore, regenera- very little blood supply to the pulp. Hence revasculariza-
tive endodontic treatment is not needed for permanent tion should not be performed when the apical foramen
immature teeth with a vital pulp which is not necrotic or is closed or almost closed. Indeed, it has been demon-
does not suffer from irreversible pulpitis, and these teeth strated that the apical foramen must be wide open, and
are more likely to benefit from treatment with apexogen- the wider the better to allow an adequate blood supply
esis (Goldstein et al., 1999; Mousivand et al., 2021). to revitalize tissues within the root canal. In a study of
replanted human incisors, it was shown that an apical
foramen width of more than 1.1 mm was needed for suc-
Normal tooth mobility and is restorable/ cessful root canal revascularization (Kling et al., 1986).
crown-­root fracture Some researchers have used K-­files to enlarge the size of
a closed apical foramen in mature adult teeth, but this
A traumatized tooth which is loose and has excessive mo- instrumentation is risky if the file tip breaks within the
bility, and/or which is non-­restorable due to the loss of periapical tissues. Furthermore, instrumentation of the
a crown or has suffered crown-­root fracture, has a poor apex is likely a redundant strategy. This is because if
prognosis, and cannot be saved using regenerative endo- the apical foramen is almost closed, it is likely that the
dontics alone, the treatments suggested by the traumatol- dentinal walls are reasonably thick and not likely to ben-
ogy guidelines should be provided (Levin et al., 2020). efit from a dentinal thickening and tooth strengthening
against fracture provided by a regenerative endodontic
treatment.
Tooth not avulsed and replanted within
15 min
Root canal can be adequately disinfected
It is frustrating for an endodontist or paediatric dentist have
a child with an avulsed tooth make an emergency den- When regenerative endodontic treatment has failed, 14%
tal visit, to discover that the avulsed permanent tooth was of the failures were attributed to a persistent infection
not cleaned and immediately replanted. Avulsed primary (Wikström et al., 2022), which can also be stated as fail-
teeth should never be replanted (Hammel & Fischel, 2019). ure to adequately disinfect necrotic and infected tissues
Although many articles discuss the benefits of storage media from the root canal. The disinfection of the root canals
for avulsed teeth, avulsed permanent teeth should not be can be effectively accomplished by placing calcium hy-
kept extra-­oral in storage media. Replanted avulsed perma- droxide, or a broad-­spectrum triple antibiotic paste con-
nent teeth can suffer from healing complications; periapical taining of Ciprofloxacin, Metronidazole, Minocycline (do
radiolucency, external root resorption, ankylosis, which can Couto et al., 2021; Windley III et al., 2005) to a final con-
be minimized by immediately replanting the permanent centration of 0.1 mg/ml, placed inside the root canal for
teeth, especially within 15 min of avulsion (Cho et al., 2016). 1–­4 weeks (AAE, 2016). Potentially necrotic and infected
tissue is also irrigated from the root canal using 20 ml of
1.25% NaOCl using hand and rotary files, followed by a
Root canal apex is open wider than flush of 17% EDTA, and a rinse of saline. Clearly, if there
1.1 mm and bleeding fills the root canal are inaccessible infected and necrotic tissue remnants
within the root canals, these are a potential source of
Following regenerative endodontic treatment, 25% of infection, and if they cannot be removed, the root canal
the treatment failures were attributed to the absence of cannot be adequately disinfected. If the root canal cannot
 |

13652591, 0, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/iej.13809 by CAPES, Wiley Online Library on [12/02/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
MURRAY    7

be adequately disinfected, then regenerative endodontics materials for apexification, revealed that all three of these
treatment will likely fail, and be observed as a flareup, biomaterials had similar success rates above 90% (Shaik
with swelling lesion, abscess, and pain. Therefore, apexi- et al., 2021), which is a 10% improvement, above the 80%
fication should be provided to immature permanent teeth reported success rate of calcium hydroxide for apexifica-
with a necrotic pulp if the root canal cannot be adequately tion (Damle et al., 2016). A drawback of using calcium
disinfected. hydroxide for apexification is that it requires multiple ap-
pointments to replace the calcium hydroxide, whereas the
MTA need only be applied once (Guerrero et al., 2018).
Summary for case selection criteria to However, the practical limitations of apexification are that
attempt regenerative endodontics it cannot promote maturation of the immature tooth root,
and thus cannot increase the thickness of the dentinal
The case selection criteria are a work in progress be- walls to strengthen the tooth. Therefore, apexification can
cause the limitations of regenerative endodontics are be an optimal endodontic treatment for immature teeth
still being discovered. The case selection criteria for with a necrotic pulp where the root dentinal walls are
regenerative endodontics discussed above, are summa- already thick enough to resist a fracture. Nevertheless,
rized in Figure 1. apexification is not an optimal endodontic treatment for
fragile immature teeth with very thin dentinal roots, be-
cause it cannot mineralize the thickness of the dentinal
DI F F E R E N T IAL DIAG N OSIS roots to strengthen the tooth to resist a fracture.
TO S E L ECT EN DODON T IC
T R E AT M E NT S FOR IMMAT U R E
T E ET H APEXOGENESIS

The most suitable endodontic treatments for immature Apexogenesis is a procedure which debrides the coronal
teeth will vary depending on the case selection criteria, injured pulp from the root canal of an immature perma-
the status of the dental pulp as vital or non-­vital or having nent tooth with a vital pulp. The removal of the superfi-
irreversible pulpitis with a poor prognosis for continued cial injured and or infected pulp is necessary to prevent
pulp vitality, and the developmental stage of maturity of the spread of necrosis/infection/irreversible pulpitis to
the root canals. This is because immature teeth that are allow the remaining vital, uninfected, and uninflamed
almost fully developed, with thick and strong dentinal pulp to continue the maturation and physiological devel-
walls are better able to resist tooth fracture. However, very opment of the roots (Goldstein et al., 1999; Mousivand
immature teeth at an early stage of development, with et al., 2021). Apexification and apexogenesis are not
thin and weak dentinal walls are more prone to fracture, comparable treatments for the same tooth. This is be-
and these fragile teeth would most benefit from regen- cause unlike apexification discussed above, apexogenesis
erative endodontic treatment to continue dentinogenesis is a vital pulp-­capping treatment, whereas apexification
to strengthen the teeth. Thus, regenerative endodontic is a non-­vital (necrotic pulp) treatment. Apexogenesis
treatment is not always optimal for immature teeth, and maintains the survival of the vital pulp to continue root
differential diagnosis should be used to select the most ap- maturation and thickening, which can strengthen the
propriate treatment with the highest success rate between tooth to resist fracture. Thus, because the pulp is still
apexification, apexogenesis, conventional root canal treat- vital and able to mineralize root dentine, there is also no
ment, Cvek partial pulpotomy, and regenerative endodon- rational justification for providing a regenerative endo-
tics (Figure 2). dontic treatment or a conventional root canal obturation
treatment. The long-­term success rate of apexogenesis in
anterior teeth and posterior teeth was between 82.5% and
A P E X I F I C ATION 96.4% (Mousivand et al., 2021).

The goal of an apexification is to debride the necrotic pulp

from immature permanent teeth, to effectively disinfect C V EK PARTIAL PULPOTOMY
the root canal, and to obturate the root canals with cal-
cium hydroxide, MTA, or a bioceramic root repair mate- Cvek partial pulpotomy is a vital pulp procedure which
rial, to induce a calcified barrier to help save the tooth debrides 2 mm of coronal injured pulp from a root canal.
(Rafter, 2005; Shaik et al., 2021). A meta-­analysis which The removal of the superficial injured pulp will allow
compared MTA and Endosequence bioceramic root repair the remaining vital pulp to continue the maturation
 |

13652591, 0, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/iej.13809 by CAPES, Wiley Online Library on [12/02/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
8    REGENERATIVE ENDODONTICS

FIGURE 2 Flow chart for selecting appropriate endodontic treatments

and physiological development of the roots (Mejàre & CONVENTIONAL NON-­S URGIC AL
Cvek, 1993; Sari, 2002). Cvek partial pulpotomy is simi- ROOT CANAL TREATMENT
lar to Apexogenesis in that it removes some coronal pulp,
leaving a vital healthy pulp in the roots of immature The gold standard treatment for most mature teeth with
teeth, the only difference is that the amount of partial-­ a painful and/or necrotic pulp is a conventional non-­
pulpotomy using the Cvek treatment is fixed at 2 mm, surgical root canal treatment (Nagendrababu et al., 2020).
whereas, the amount of partial-­pulpotomy for apexog- It is a necrotic pulp and irreversible pulpitis procedure
enesis can be less or greater according to the skill of the for mature teeth which uses instruments, irrigants, and
clinician and relative to the extent of damage to the im- chelating agents to debride infected tissues, and disinfects
mature tooth trauma because of the size and position of the root canal by cleaning, shaping, sealing, and obtura-
the caries or fracture (Shah et al., 2022). The long-­term tion (Metzger et al., 2010; Peters, 2004). The long-­term
healing success of Cvek partial pulpotomy can exceed survival rates for teeth following non-­surgical endodon-
93% (Mejàre & Cvek, 1993). tic treatment can exceed 86%, and the tooth survival after
 |

13652591, 0, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/iej.13809 by CAPES, Wiley Online Library on [12/02/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
MURRAY    9

TABLE 2 Advantages of regenerative endodontics

non-­
surgical endodontic retreatments can exceed 78%
(Elemam & Pretty, 2011). It is a root canal revascularization alternative treatment to
apexification
It has the potential to save fragile immature permanent teeth
REG E NE R ATIVE E N DODON T ICS over the long term by continuing root development to
thicken the canal walls to help protect them against fracture

This is a necrotic pulp and irreversible pulpitis procedure It can heal periapical lesions and continue apex development
which debrides tissues from the root canal, disinfects the It can restore sensitivity to teeth
root canal, instruments the periapical tissues through It can prevent the loss of permanent teeth in children and young
the open root apical foramen to cause bleeding into the adults and their lifelong need for dental implants, bridges, or
canal to revascularize it. In addition, it introduces a dentures
scaffold or biological procedure within the root canal to
promote vital tissue formation which will continue the
deposition of mineral to strengthen ­dentine and grow should always be provided when these treatments are
the roots of immature teeth (Namour & Theys, 2014; more likely to benefit the patient because they can be
Wigler et al., 2013; Wikström et al., 2022). In a study more successful than regenerative endodontics (Murray
which compared blood clot revascularization (BCR), & Garcia-­Godoy, 2012).
versus platelet-­rich plasma (PRP), versus platelet-­rich
fibrin (PRF), it was discovered that RPR and PRF may
be more successful in terms of accomplishing apical clo- CONCLUSION:
sure or a decrease in the size of the root apex, periapical CONTRAINDICATIONS,
healing response, and root lengthening (Murray, 2018). CONSIDERATIONS, AND
In a case report by Prasad et al. (2018) apical bridge for- ADVANTAGES OF REGENERATIV E
mation only occurred in incisors treated with PRF. ENDODONTICS
The outcomes of regenerative endodontic treatment
can be highly variable, from a high pooled survival and Regenerative endodontics will likely continue to be highly
healing rate of 97%, whereas, if 20% radiographic changes controversial, even as the knowledge gap of practitioners
were used as a cut-­off point, there were only 16% root and researchers decrease. Thus, ultimately the decisions
lengthening and 40% root thickening (Ong et al., 2020). A and choices for the endodontist, must be based on their
meta-­analysis and systematic review by Tong et al. (2017) own skills and knowledge, and the willingness of the pa-
concluded that many knowledge gaps still exist within tient, their parents, and guardians to save their trauma-
published studies, and current published evidence is un- tized tooth.
able to provide definitive conclusions on the predictabil- In the interests of keeping this review concise and un-
ity of regenerative endodontic outcomes. Furthermore, biased, highlighting the good, the bad, and the ugly facets
a meta-­ analysis and systematic review by Torabinejad of regenerative endodontics has been undertaken. Some
et al. (2017) concluded that the literature lacks high-­ known advantages of regenerative endodontics are sum-
quality studies with a direct comparison of MTA and re- marized in Table 2, while some practical tips, contraindi-
generative endodontic treatment. There is no consensus cations, and considerations for regenerative endodontics
in using regenerative endodontic procedures in previously are summarized in Table 3.
treated immature teeth, as at a long-­term recall visit, five
retreated teeth showed partial or complete apical closure AUTHOR CONTRIBUTIONS
(Cymerman & Nosrat, 2020). The treatment options for The corresponding author is the sole contributor for this
failing regenerative endodontic procedures, include apexi- article.
fication, or repeating the regenerative endodontic proce-
dure. Regenerative endodontic retreatment was successful CONFLICT OF INTEREST
in three cases (Chaniotis, 2017) and a case report (Nosrat The author is not attempting to sell any product or service
et al., 2021). to readers. Furthermore, the author denies a conflict of
Regenerative endodontics has the unique potential interest that would cause an undue bias, such as the prob-
advantage of being able to continue the root develop- lems and failures of regenerative endodontics to be hidden
ment in immature permanent teeth, thereby potentially from readers of this review. For the purposes of full dis-
saving the teeth for the lifetime of the patient. However, closure to readers, the author was involved in drafting the
in conventional endodontic root canal treatment, Cvek guidelines for the American Association of Endodontists
partial pulpotomy, apexogenesis, and apexification, (AAE) on regenerative endodontics. The author has
 |

13652591, 0, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/iej.13809 by CAPES, Wiley Online Library on [12/02/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
10    REGENERATIVE ENDODONTICS

T A B L E 3 Contraindications and considerations for DATA AVAILABILITY STATEMENT

regenerative endodontics Data sharing not applicable to this article as no datasets
Never provide regenerative endodontics to fully developed were generated or analysed during the current study.
teeth, because the body of literature has established that
traditional endodontic treatment has a better prognosis ETHICAL APPROVAL
Consider if the immature permanent tooth with a necrotic This review did not require ethical approval, because it
pulp can be saved with apexification or conventional non-­ does not present any identifiable human subjects' data.
surgical root canal treatment, before attempting regenerative However, as a background, all prior institutional ethical
endodontics approvals have been obtained to collect all data pursuant
A failure to adequately disinfect the root canal will risk to this review, without any acts of misconduct, and with-
spreading the infection and necrosis to adjacent tissues out any rule violations by the author.
Never use full strength or undiluted disinfectants. Sodium
hypochlorite (NaOCl) must be diluted to a concentration ORCID
of 1.25% or less, and continuous suction must be used to
Peter E. Murray https://orcid.org/0000-0002-5874-2926
prevent its leakage, because of the risk of toxic chemical
injury to the vital periapical tissues
REFERENCES
Only debride the intracanal necrotic or infected tissues.
Almonaitiene, R., Balciuniene, I. & Tutkuviene, J. (2012) Standards for
Never use hand files or rotary files to instrument the root
permanent teeth emergence time and sequence in Lithuanian
canal walls or enlarge the apical foramen, because it risks
children, residents of Vilnius city. Stomatologija, 14, 93–­100.
weakening the thin dentinal walls, which may fracture the
American Association of Endodontists (AAE). (2016) AAE Clinical
tooth
considerations for a regenerative procedure. Revised 6 August
Never leave the root canals empty, because revascularization 2016. Available at: https://www.aae.org/speci​alty/wp-­conte​
will fail if bleeding cannot be established into the entire root nt/uploa​ds/sites/​2/2017/06/curre​ntreg​enera​tivee​ndodo​nticc​
canal space onsid​erati​ons.pdf
Never place donor blood in a root canal, and never add Chaniotis, A. (2017) Treatment options for failing regenerative end-
unanchored exogenous stem cells into root canals, because odontic procedures: report of 3 cases. Journal of Endodontics,
of the potentially severe health hazards 43, 1472–­1478.
Never pack the MTA below the level of the cementoenamel Cho, S.Y., Lee, Y., Shin, S.J., Kim, E., Jung, I.Y., Friedman, S. et al.
junction, because it will prevent dentine regeneration at that (2016) Retention and healing outcomes after intentional re-
weak tooth fracture point plantation. Journal of Endodontics, 42, 909–­915.
Chrepa, V., Joon, R., Austah, O., Diogenes, A., Hargreaves, K.M.,
Consider avoiding the use of minocycline for disinfecting root
Ezeldeen, M. et al. (2020) Clinical outcomes of immature
canals to help prevent subsequent tooth discoloration
teeth treated with regenerative endodontic procedures -­a San
Consider using Biodentine or other biomaterials as intracanal Antonio study. Journal of Endodontics, 46, 1074–­1084.
barrier alternatives to white MTA Clark, D. & Levin, L. (2019) In the dental implant era, why do we still
Consider restoring the cervical third of the immature tooth with bother saving teeth? Dental Traumatology, 35, 368–­375.
composite and or fibre posts where these teeth are most Cymerman, J.J. & Nosrat, A. (2020) Regenerative endodontic treat-
prone to fracture ment as a biologically based approach for non-­surgical retreat-
ment of immature teeth. Journal of Endodontics, 46, 44–­50.
Damle, S.G., Bhattal, H., Damle, D., Dhindsa, A., Loomba, A. &
spoken about regenerative endodontics to the American Singla, S. (2016) Clinical and radiographic assessment of min-
Dental Association and several other national dental and eral trioxide aggregate and calcium hydroxide as apexification
endodontic associations. The author has accepted funding agents in traumatized young permanent anterior teeth: a com-
to pursue research on several aspects of regenerative en- parative study. Dental Research Journal, 13, 284–­291.
dodontics. The author has obtained ethical approvals to do Couto, A.M., Espaladori, M.C., Leite, A.P.P., Martins, C.C., de
Aguiar, M.C.F. & Abreu, L.G. (2021) A systematic review of
supervise endodontic residents in clinical trials of regen-
pulp revascularization using a triple antibiotic paste. Pediatric
erative endodontics. The author is the holder of an expired
Dentistry, 41, 341–­353.
patent for an endodontic regeneration kit. The author has Elemam, R.F. & Pretty, I. (2011) Comparison of the success rate of
a publishing agreement with Springer-­Verlag and other endodontic treatment and implant treatment. ISRN Dentistry,
textbook publishers to write book chapters on regenera- 2011, 640509.
tive endodontics. The author's views are his own, he does Elfrink, M., Heijdra, J., Krikken, J.B., Kouwenberg-­Bruring, W.H.,
not write on behalf of any agency, ethics board, editorial Kouwenberg, H., Weerheijm, K.L. et al. (2021) Regenerative
board, endodontic or dental association. Moreover, the endodontic therapy: a follow-­up of 47 anterior traumatised
teeth. European Archives of Paediatric Dentistry, 22, 469–­477.
author is grateful for this opportunity to write this review
Goldstein, S., Sedaghat-­Zandi, A., Greenberg, M. & Friedman, S.
to disclose the problems and failures, so that they can be
(1999) Apexification & apexogenesis. The New York State Dental
prevented, to benefit patients and endodontists. Journal, 65, 23–­25.
 |

13652591, 0, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/iej.13809 by CAPES, Wiley Online Library on [12/02/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
MURRAY    11

Guerrero, F., Mendoza, A., Ribas, D. & Aspiazu, K. (2018) Mousivand, S., Sheikhnezami, M., Moradi, S., Koohestanian, N. &
Apexification: a systematic review. Journal of Conservative Jafarzadeh, H. (2021) Evaluation of the outcome of apexogenesis
Dentistry, 21, 462–­465. in traumatised anterior and carious posterior teeth using min-
Gune, N.S. & Katre, A.N. (2021) Dental practitioner's perception eral trioxide aggregate: a 5-­year retrospective study. Australian
of the compliance of pediatric patients to orofacial myother- Endodontic Journal. https://doi.org/10.1111/aej.12583
apy treatment protocols: a mixed methods study. International Murray, P.E. (2018) Platelet-­rich plasma and platelet-­rich fibrin can
Journal of Clinical Pediatric Dentistry, 14, 222–­228. induce apical closure more frequently than blood-­clot revascu-
Hammel, J.M. & Fischel, J. (2019) Dental emergencies. Emergency larization for the regeneration of immature permanent teeth:
Medicine Clinics of North America, 37, 81–­93. a meta-­analysis of clinical efficacy. Frontiers in Bioengineering
Harlamb, S.C. (2016) Management of incompletely developed teeth and Biotechnology, 11, 139.
requiring root canal treatment. Australian Dental Journal, Murray, P.E. & Garcia-­Godoy, F. (2012) Recommendations for using
61(Suppl. 1), 95–­106. regenerative endodontic procedures in permanent immature
He, L., Kim, S.G., Gong, Q., Zhong, J., Wang, S., Zhou, X. et al. traumatized teeth. Dental Traumatology, 28, 33–­41.
(2017) Regenerative endodontics for adult patients. Journal of Murray, P.E., Garcia-­ Godoy, F. & Hargreaves, K.M. (2007)
Endodontics, 43, S57–­S64. Regenerative endodontics: a review of current status and a call
Hugo, F.N., Hilgert, J.B., de Sousa, M. & Cury, J.A. (2009) Oral for action. Journal of Endodontics, 33, 377–­390.
status and its association with general quality of life in older Nagendrababu, V., Segura-­Egea, J.J., Fouad, A.F., Pulikkotil, S.J. &
independent-­living south-­Brazilians. Community Dental and Dummer, P. (2020) Association between diabetes and the out-
Oral Epidemiology, 37, 231–­240. come of root canal treatment in adults: an umbrella review.
Kandemir Demirci, G., Güneri, P. & Çalışkan, M.K. (2020) International Endodontic Journal, 53, 455–­466.
Regenerative endodontic therapy with platelet rich fibrin: case Namour, M. & Theys, S. (2014) Pulp revascularization of immature
series. The Journal of Clinical Pediatric Dentistry, 44, 15–­19. permanent teeth: a review of the literature and a proposal of
Kling, M., Cvek, M. & Mejare, I. (1986) Rate and predictability of a new clinical protocol. Scientific World Journal, 2014, 737503.
pulp revascularization in therapeutically reimplanted perma- Nosrat, A., Bolhari, B., Saber Tahan, S., Dianat, O. & Dummer, P.M.H.
nent incisors. Endodontics & Dental Traumatology, 2, 83–­89. (2021) Revitalizing previously treated teeth with open apices:
Lawley, G.R., Schindler, W.G., Walker, W.A., III & Kolodrubetz, D. a case report and a literature review. International Endodontic
(2004) Evaluation of ultrasonically placed MTA and fracture Journal, 54, 1782–­1793.
resistance with intracanal composite resin in a model of apexi- Ong, T.K., Lim, G.S., Singh, M. & Fial, A.V. (2020) Quantitative as-
fication. Journal of Endodontics, 30, 167–­172. sessment of root development after regenerative endodontic
Levin, L., Day, P.F., Hicks, L., O'Connell, A., Fouad, A.F., therapy: a systematic review and meta-­ analysis. Journal of
Bourguignon, C. et al. (2020) International association of den- Endodontics, 46(12), 1856–­1866.e2.
tal traumatology guidelines for the management of traumatic Peters, O.A. (2004) Current challenges and concepts in the prepa-
dental injuries: general introduction. Dental Traumatology, 36, ration of root canal systems: a review. Journal of Endodontics,
309–­313. 30, 559–­567.
Lodi, G., Azzi, L., Varoni, E.M., Pentenero, M., Del Fabbro, M., Prasad, J., de Ataide, I.N., Chalakkal, P. & Likhyani, L.K. (2018)
Carrassi, A. et al. (2021) Antibiotics to prevent complications Comparison between the outcomes of two platelet-­rich con-
following tooth extractions. Cochrane Database Systemic centrates on apexogenesis in young permanent incisors requir-
Review, 24, CD003811. ing endodontic retreatment. Contemporary Clinical Dentistry,
Mayya, A., Naik, R., Paul, M.P., Amin, S. & Mayya, S.S. (2021) 9(Suppl. 1), S156–­S159.
Knowledge, attitude, and perception among endodontists to- Rafter, M. (2005) Apexification: a review. Dental Traumatology, 21,
ward regenerative endodontics: a cross-­ sectional survey of 1–­8.
four Indian universities. Journal of International Society of Ricucci, D., Loghin, S. & Siqueira, J.F., Jr. (2014) Correlation between
Preventive and Community Dentistry, 11, 68–­76. clinical and histologic pulp diagnoses. Journal of Endodontics,
Mejàre, I. & Cvek, M. (1993) Partial pulpotomy in young perma- 40, 1932–­1939.
nent teeth with deep carious lesions. Endodontics & Dental Sari, S. (2002) Cvek pulpotomy: report of a case with five-­year fol-
Traumatology, 9(6), 238–­242. low-­up. ASDC Journal of Dentistry for Children, 69, 27–­11.
Meschi, N., EzEldeen, M., Garcia, A.E.T., Lahoud, P., Van Gorp, G., Shah, A., Peacock, R. & Eliyas, S. (2022) Pulp therapy and root canal
Coucke, W. et al. (2021) Regenerative endodontic procedure treatment techniques in immature permanent teeth: an update.
of immature permanent teeth with leukocyte and platelet-­ British Dental Journal, 232, 524–­530.
rich fibrin: a multicenter controlled clinical trial. Journal of Shaik, I., Dasari, B., Kolichala, R., Doos, M., Qadri, F.,
Endodontics, 47, 1729–­1750. Arokiyasamy, J.L. et al. (2021) Comparison of the success
Metzger, Z., Zary, R., Cohen, R., Teperovich, E. & Paqué, F. (2010) rate of mineral trioxide aggregate, endosequence bioceramic
The quality of root canal preparation and root canal obturation root repair material, and calcium hydroxide for apexification
in canals treated with rotary versus self-­adjusting files: a three-­ of immature permanent teeth: systematic review and meta-­
dimensional micro-­computed tomographic study. Journal of analysis. Journal of Pharmacy & Bioallied Sciences, 13(Suppl
Endodontics, 36, 1569–­1573. 1), S43–­S47.
Mohammadi, Z., Assadian, H., Bolhari, B., Sharifian, M., Silva-­Junior, M.F., Sousa, A.C.C., Batista, M.J. & Sousa, M.D.L.R.
Khoshkhounejad, M. & Chitsaz, N. (2021) Unpredictable out- (2017) Oral health condition and reasons for tooth extraction
comes of a regenerative endodontic treatment. Case Reports in among an adult population (20–­ 64 years old). Cien Saude
Dentistry, 2021, 2478310. Coletiva, 22, 2693–­2702.
 |

13652591, 0, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/iej.13809 by CAPES, Wiley Online Library on [12/02/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
12    REGENERATIVE ENDODONTICS

Tong, H.J., Rajan, S., Bhujel, N., Kang, J., Duggal, M. & Nazzal, H. failures and long-­term outcomes-­a longitudinal cohort study.
(2017) Regenerative endodontic therapy in the management International Endodontic Journal, 55, 630–­645.
of nonvital immature permanent teeth: a systematic review-­ Windley, W., III, Teixeira, F., Levin, L., Sigurdsson, A. & Trope, M.
outcome evaluation and meta-­analysis. Journal of Endodontics, (2005) Disinfection of immature teeth with a triple antibiotic
43, 1453–­1464. paste. Journal of Endodontics, 31, 439–­443.
Torabinejad, M., Nosrat, A., Verma, P. & Udochukwu, O. (2017) Yu, C. & Abbott, P.V. (2007) An overview of the dental pulp: its func-
Regenerative endodontic treatment or mineral trioxide aggre- tions and responses to injury. Australian Dental Journal, 52(1
gate apical plug in teeth with necrotic pulps and open apices: Suppl), S4–­S16.
a systematic review and meta-­analysis. Journal of Endodontics,
43, 1806–­1820.
Trope, M. (2008) Regenerative potential of dental pulp. Pediatric How to cite this article: Murray, P.E. (2022)
Dentistry, 30, 206–­210. Review of guidance for the selection of regenerative
Weibert, R.T. (1992) Oral anticoagulant therapy in patients undergo- endodontics, apexogenesis, apexification,
ing dental surgery. Clinical Pharmacy, 11, 857–­864.
pulpotomy, and other endodontic treatments for
Wigler, R., Kaufman, A.Y., Lin, S., Steinbock, N., Hazan-­Molina, H.
& Torneck, C.D. (2013) Revascularization: a treatment for per-
immature permanent teeth. International
manent teeth with necrotic pulp and incomplete root develop- Endodontic Journal, 00, 1–12. Available from:
ment. Journal of Endodontics, 39, 319–­326. https://doi.org/10.1111/iej.13809
Wikström, A., Brundin, M., Romani Vestman, N., Rakhimova, O.
& Tsilingaridis, G. (2022) Endodontic pulp revitalization in
traumatized necrotic immature permanent incisors: early