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Review Article

Mod Res Dent

ISSN 2637-7764

Managements of Immature Apex: a Review
Kareem A Mohamed Kamel1* and Rasha M Abuzied2
1

Former Dental Regional Adviser, Head of Royal Dentists Institute, Egypt

2

Restorative Dentistry Department, Royal Dentists Institute, Egypt*Corresponding author: Kareem A Mohamed Kamel, Dental Regional Adviser, Royal Dentists Institute, 6th of October City, Cairo, Egypt
Submission:

July 08, 2017 ; Published:

October 20, 2017

Abstract
This paper reviews the rationale and techniques for treatment of the non-vital immature tooth. The importance of careful case assessment andaccurate pulpal diagnosis in the treatment of immature teeth with pulpal injury cannot be overemphasized. The treatment options starts from indirect
pulp capping, direct pulp capping, partial pulpotomy, full pulpotomy, apex genesis, apexification and ending up with revitalization. Describing thetechniques, indications and the drawbacks of each treatment option.

Root Development
Root development commences after the completion of enamelformation. The cells of inner and outer enamel epithelia unite atpoint forming cervical loop, begin to proliferate and form a structure
known as the Hertwig epithelial sheath. This sheath determines
the size and shape of root/s of the tooth [1]. Apical root closure iscompleted approximately 2-3 years after tooth eruption [2].

Causes of Pulpal Disease

The major irritants of pulp tissue include various bacteria,
trauma, dental procedures generating thermal stimulation andchemical agent. Irritation of pulp tissue results in major changes inpulp microcirculation that can lead to pulp necrosis and arrest root
formation [3].

Dental caries is the most prevalent microbial infectious
disease. As the caries lesion approximates the pulp, there is acuteexacerbation of the precedent chronic inflammation characterized
by an influx of neutrophils [4]. In the presence of severe
inflammation, focal microabscesses form and eventually coalesce
leading to progressive pulpal necrosis.
Restorative procedures can also affect pulpal tissue. Thermal
injury may occur as result of tooth preparation or finishingprocedures using dry cutting, dull burs, deep periodontal curettage,orthodontic movement, or lasers and air abrasion devices [5].

Chemical irritants of pulp include cavity cleansers such as
alcohol, chloroform and hydrogen peroxide as well as some
substance in restorative materials and cavity liner [6]. One key
requirement of a successful restorative procedure is to cause
minimal additional irritation of the pulp so as not to interferewith normal pulpal healing. Crown-fracture teeth with or without
pulp exposure and associated luxation injury experience a greater
frequency of pulp necrosis [7]. However immature permanent tooth
has considerable capacity to heal after traumatic pulp exposure, so
conservative pulp therapies are important to preserve pulp vitality
and allow for continued root formation.

Clinical Tests to Determine Pulp Condition

Pulpal conditions and stage of root development are the major
factors in the selection of treatment plan [8]. However with early
diagnosis and intervention, pulp preservation strategies promote anenvironment for continued dentine apposition and root formation.

Diagnosis begins with a careful medical examination and any
implications related to the anticipated treatment. A Thorough dental
history including all symptoms and characteristics of associatedpain is essential. Visual examination of both soft and hard tissue
for the presence or absence of swelling, crown discoloration andcaries.

Mobility and periodontal probing can provide information
regarding the health of status pulp. Electric and thermal tests are oflimited value due to their varied responses in permanent teeth withimmature apex [9]. After traumatic injuries electric and thermal
pulp tests may be unreliable, only generalized impressions may begained from these tests [10].

Attempts have been made to use laser Doppler flowmetry(LDF) for measurement of blood flow in traumatized teeth as thiswould provide more accurate readings [11]. The pulse oximeter
also offers accurate means of monitoring pulp vitality by recording
the oxygenation of pulpal flow [12].

Copyright © All rights are reserved by Kareem A Mohamed Kamel 1(1). MRD.000503. 2017.

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Mod Res Dent

Modern Research in DentistryRadiographic examination of teeth requires good quality
periapical and bitewing radiographs. These radiographs reveal thestatus of periapical tissues, presence and proximity of pulpal caries
and stage of root development. The use of cone beam computed
tomography should provide more accurate information regarding
the condition of periapical tissues and root formation compared to
2-dimension conventional radiographs [13].
However it is still difficult to determine if the pulp isreversibly or irreversibly affected [14]. Moreover children may
have unreliable clinical symptoms and exaggerated responses topercussion, palpation and pulp tests that do not correlate well withhistopathological condition of pulp in immature teeth [15].

A recent systematic review [16] aimed to appraise the diagnostic
accuracy of sign/symptoms, pulp tests to determine the conditionof pulp in teeth affected by deep caries, trauma and other types of
injuries showed that there is insufficient evidence to assess thevalue of toothache or abnormal reaction to hot/cold stimulation for
determining pulp condition. However it is hoped that by combining
the result of history, examination and diagnostic tests, an accurate
clinical diagnosis of pulp vitality can be made in most cases.

Treatment of Teeth with Vital Pulp and Open Apices

When pulp exposure occurs in immature tooth due to caries ortrauma, the exposed pulp can heal if protected from further injury.
Treatment of immature teeth has changed dramatically in recent
years as new concepts and materials have developed. Vital pulp
therapies are the treatment of choice for traumatized and carious
teeth with vital pulps and open apices [17]. The approaches include
indirect pulp capping in deep caries cavities and direct pulp cappingor pulpotomy in cases of pulp exposure.
The key to the success of vital pulp therapy might partly be strictcase selection and proper treatment protocol. Vital pulp therapy
should not only be performed in teeth with signs and symptoms ofreversible pulpitis [18]. This may be against the traditional schoolof thought that vital pulp therapy should only be performed inteeth reversible pulpitis [19]. Several studies included teeth withsigns of irreversible pulpitis such as teeth with spontaneous pain
[20-22], and teeth that were positive to percussion [20,21] weretreated successfully. In full pulpotomy studies [22-24], teeth withperiodical radiolucency lesions were treated successfully withweighted pooled success rate of 92% [25].
Moreover, histological studies demonstrate that curiously
exposed vital pulp was not always completely infected. Occasionally
the inflammation was localized adjacent to carious lesion, notspreading to the whole coronal or reticular pulp [25,26].

Apexogenesis

Apex=root end, genesis=formation. Apex genesis is defined as “avital pulp therapy procedure to encourage continued physiologicaldevelopment and formation of the root end” [18]. Only inflamed
pulp tissue should be removed and bioactive material is placed overremaining healthy pulp tissue.
The goals of apex genesis are [19]:a)Allow continued development of root length.

b) Maintain pulp vitality, thus allow continued deposition ofdentin.
c)
Promoting root end closure, thus creating natural apicalconstriction.
d)Generating Dentine Bridge at the site of pulpotomy.

Treatment of Teeth with Necrotic Pulp and Open Apices
Incomplete root development can provide a challenging clinicalsituation in treatments [20].
A.

Cleaning and shaping of blunderbuss canal is difficult.

C.

Thin, fragile dentine walls are liable to fracture.

B.
Necrotic debris in wide root canal is difficult to completely
disinfect.
D.

Risk of extending materials beyond apex.

Three techniques were reported to obdurate an immature
tooth which involved the use of a root filling material without theinduction of the apical closure [21].
a.
Placement of large gutta-percha or customized guttapercha cone with sealer at the apex.
b.
c.

Placement of gutta-percha with sealer short of apex.
Periodical surgery.

However these techniques will not provide apical barrier.
Another two techniques were reported aimed to provide apicalbarrier [21].
i.
Placement of calcium hydroxide to induce mineralizedapical barrier.

ii.
Placement of biocompatible material such as dentine
chips against which a root filling is placed.
iii. Until recently, the traditional approach to treat immature
apex is apexification [22].

Apexification

Apexification is histological term defined as “a method to induce
a calcified barrier in a root with open apex” [18]. The infected
necrotic pulp is removed up to the apex by means of mechanicaldebridement and anti septic chemical irrigation [22].

Apical hard tissue barrier formation following apexificationis reparative process of the dentine-pulp complex [23]. However,continued physiologic root development of immature permanent
tooth with infected necrotic pulps and apical periodontitis after
apexification procedure with calcium hydroxide was reported [24].

Contemporary Materials
Calcium hydroxide

Calcium hydroxide is the most popular material to induce
normal root development [25]. Calcium hydroxide is white odorlesspowder and is chemically classified as strong base with PH 12.5; incontact with aqueous fluids it dissociate into calcium and hydroxylions [25].

How to cite this article: Kareem A M K, Rasha M A. Managements of Immature Apex: a Review. Mod Res Dent. 1(1). MRD.000503. 2017.
DOI: 10.31031/MRD.2017.01.000503

8

Mod Res Dent

Modern Research in Dentistry
The antimicrobial activity of calcium hydroxide is related to therelease of highly reactive hydroxyl ions in aqueous environment
which mainly affect cytoplasm membranes, proteins and DNA ofbacterial cells [26].
The mineralizing action of calcium hydroxide is directly
influenced by its high PH. The alkaline PH not only neutralizes acids
from osteoclasts but also activate alkaline phosphates enzyme
which plays a role in hard tissue formation [27]. However, calcium
ions present in Dentine Bridge originated from systemic circulation[28].

Calcium hydroxide is biocompatible, but unfortunately has
low compressive stress that is not compatible with condensation
forces of amalgam, also solubility of calcium hydroxide in fluids is aproblem as a reliable seal cannot be achieved so a good coronal sealis required in case of vital pulp therapy [29].

Mineral trioxide aggregate

Mineral trioxide aggregate is bioactive material that influences
its surrounding environment. MTA is currently marked in two
forms: white and gray. MTA was introduced in gray but because ofits discoloration potential, White MTA was developed [30]. Gray
MTA basically consists of declaim, tricalcium silicate and bismuthoxide, whereas white MTA is composed of tricalcium silicate andbismuth oxide [31].

MTA is prepare by mixing its powder with sterile water in a 3:1
powder to liquid ratio that result in a colloid gel that solidifies into
hard structure [32]. The PH value of MTA is 10.2 after mixing. Thisvalue rises to 12.5 at three hour [33].
The mean setting time of MTA is two hours and 45 minutes.
At 24 hours MTA has the lowest compressive strength among
materials (40MPa), but increased after 21 days (67MPa) [33]. A
recent study reported that compressive strength of MTA is higher
when mixed mechanically and placed by ultrasonic agitation thanwhen mixed manually and placed without ultrasonic agitation [34].

The solubility of MTA is influenced by powder to water ratio.
In fact, higher water to powder ratios increase MTA porosity andsolubility [34]. MTA has an antibacterial and antifungal effect.
Lowering the powder to liquid ratio might adversely affect theantibacterial and antifungal properties of MTA [35]. MTA has
Cementoconductivity and cementoinductivity properties that havebeen confirmed when reasonable concentration of material (lessthan 20mg/ml) has been used. MTA offers a biological substrate
for cement oblasts attachment and growth as well as production ofmineralized matrix gene (osteocalcin) and protein expression over
MTA [36].

Indirect Pulp Capping

Indirect pulp capping is “procedure in which a material is placedon thin partition of remaining carious dentine that if removed
might expose the pulp in immature permanent teeth” [18]. Also
called “stepwise technique”.

Indications [37]a.

b.

Permanent teeth.

Normal response to pulp tests.

c.
No symptoms of pulpitis or with diagnosis of reversible
pulpitis.
d.
Deep caries lesion radio graphically with no apical
pathosis.

Technique (Figure 1)

This approach involves 2 steps process. The first step, the toothis anesthetized and isolated with rubber dam, the carious dentine isremoved completely from the dentin-enamel junction and only thesoftest infected dentine is excavated, leaving a carious layer overthe pulp. Calcium hydroxide is then applied to the carious dentine.
The objective is to change the cryogenic environment in order todecrease number of bacteria and close remaining caries from
biofilm of the oral cavity. Subsequent radiographic reevaluation toensure formation of Dentine Bridge and normal periodical status.

Figure 1: Indirect pulp therapy.
a)Preoperative radiograph of maxillary first molar showing deep occlusal caries.
b)
Caries are removes except a layer immediately over the pulp.
c)
CH is applies to caries dentine.
d)Postoperative radiograph after 1 year, the remaining caries are removes and permanent restoration is placed.

How to cite this article: Kareem A M K, Rasha M A. Managements of Immature Apex: a Review. Mod Res Dent. 1(1). MRD.000503. 2017.
DOI: 10.31031/MRD.2017.01.000503

9Mod Res Dent

Modern Research in Dentistry
The second step, after 6 to 12 months allowing sufficient time
for tertiary dentine formation, the carious lesion is reentered andthe caries is removed to the formed dentine bridge and permanent
restoration is placed [38]. However, what is critical to both steps of
excavation is the placement of well sealed restoration [39].
One step indirect pulp capping was also reported [40], which
involves minimal removal of caries and sealed with permanent
filling restoration without a return for additional excavation. Two
steps indirect pulp capping is also questioned of whether or not tohave any advantage over one step treatment regimen. In fact, there
may be two important disadvantages for the two steps technique.
The first is the requirement of patient compliance and the assuranceof return visit after 6-12 months. Secondly, a bacterial-tight seal isessential between visits. Thirdly, the two steps treatment is more
expensive, requiring twice as much as operator and office time [41].

Mode of action

When thickness of remaining dentine including reactionary
dentine between the front of bacterial penetration and the pulp
is 1.1mm or more, the pulpal inflammatory response to bacterial
infection of the dentinal tubules is negligible. However, when thebacterial penetration in the dentinal tubules reaches to within
0.5mm from the pulp, there is significant increase in the pulpal
inflammation [42].

Indirect pulp capping intended to protect the primaryodontoblast and the pulp from further injury. When the infected
dentine is removed, the affected dentine can rematerialize andpromote odontoblasts to form reactionary dentine formation at thepulp-dentine junction [43]. Reactionary dentin genesis is usuallycaused by milder injury of the dentin-pulp complex as slowly.
The second step, after 6 to 12 months allowing sufficient time for
tertiary dentine formation, the carious lesion is reentered and thecaries is removed to the formed dentine bridge and permanent
restoration is placed [38]. However, what is critical to both steps
of excavation is the placement of well sealed restoration [39]. One
step indirect pulp capping was also reported [40], which involves
minimal removal of caries and sealed with permanent filling
restoration without a return for additional excavation. Two steps
indirect pulp capping is also questioned of whether or not to haveany advantage over one step treatment regimen. In fact, there may
be two important disadvantages for the two steps technique. The
first is the requirement of patient compliance and the assuranceof return visit after 6-12 months. Secondly, a bacterial-tight sealis essential between visits. Thirdly, the two steps treatment ismore expensive, requiring twice as much as operator and officetime [41]. Reactionary dentin genesis is usually caused by milder
injury of the dentin-pulp complex as slowly progressive caries,
cavity preparation and biomaterial used as indirect pulp capping
agents [44]. Reactionary dentin genesis is secreted by functional
up regulation of surviving primary odontoblasts, stimulated bysignaling molecules such as growth factor proteins and bioactive
molecules released from dentine matrix during injury to the dentinpulp complex [44].

Treatment outcome
In a study [45] for long term the survival of indirect pulp
treatment performed in primary and permanent teeth with clinicallydiagnosed deep caries, showed survival rate of 96% for 86 primarymolars and 93% for 34 permanent molars, it was also found thatglass monomer cement may be preferred to calcium hydroxide (CH)
as it prevents micro leakage when compared with CH. Many studies[46] was reported to determine whether complete excavation ofcaries has any advantage over stepwise treatment in an attempt to
avoid pulp exposure if possible. A critical review [47] of treatment
of deep caries by complete excavation or partial removal indicatethat complete removal of infected dentine approaching the pulp is
not required for successful caries removal. However, in systematic
review [48] of caries and pulp treatment from Cochrane Databaseindicate lack of randomized clinical trials to support incomplete
removal of caries.
In another systematic review [49] from Cochrane Databaseindicate that partial removal of caries is preferable to complete
caries removal in deep caries. The review also indicated that studies
used one step indirect pulp therapy did not reported adverse
consequences over the two steps indirect pulp therapy.
In a recent randomized clinical trial [50] comparing complete
excavation of deep caries with stepwise excavation gave less successrate (62.4%) for complete excavation than stepwise excavation(74.1%).

Direct Pulp Capping

Direct pulp capping is defined as “treatment of exposed vital
pulp by sealing the pulpal wound with material such as mineral
trioxide aggregate or calcium hydroxide to facilitate the formationof reparative dentine and maintain pulp vitality” [18].

Indications [37]a.

b.

Restorable permanent teeth.

Carious or traumatic exposure with vital pulp.

c.
No symptoms of pulpitis or with diagnosis of reversible
pulpits.

Technique (Figure 2 & 3)

The tooth is anaesthetized and isolated with rubber dam. All
caries and undermined enamel are removed with low speed roundcarbide bur and excavator. Preferably, caries detector dye is applied
for 10 seconds on dried caries dentine, and then all stained dentine
is removed [51]. Bleeding will often occur with small exposuresand can be controlled by placement of cotton pellet moisture with
3-6% sodium hypochlorite for 10-20 seconds. 2% chlorhexidine or
0.9% saline can be also used to stop bleeding. None of these agentsnegatively affected pulp healing at 90 days [52]. This step can be
repeated for 10 minutes. If homeostasis is achieved within 10
minutes hard setting calcium hydroxide is placed over pulpal tissue
and sealed with permanent restoration [53]. If MTA will be as direct
pulp capping agent, two steps approach will be taken. The first step,

How to cite this article: Kareem A M K, Rasha M A. Managements of Immature Apex: a Review. Mod Res Dent. 1(1). MRD.000503. 2017.
DOI: 10.31031/MRD.2017.01.000503

10Mod Res Dent

Modern Research in Dentistry
MTA should be mixed according to the manufacturer’s instruction.
MTA is placed directly over exposed pulp tissue and surrounding
dentine. MTA should have at least 1.5mm thickness.

Figure 2: Direct pulp capping in lower premolar.
a) A premolar tooth capped directly with MTA. B) Histologic
section after six months shows formation of dentine bridge.

Figure 3: Direct pulp capping in lower molar. a) Preoperative
radiograph shows extensive caries.
b) The decay was removed and pulp exposure was cappedby MTA.

A circumferential region of dentine and enamel approximately
1.5mm should be cleared of MTA; this will provide adequate areafor efficient seal of the restoration. Flat moist cotton is placed overentire MTA and strong interim restoration is placed. The second
step will be after 1 to 10 days. The tooth is examined for any signs
or symptoms and then interim restoration and cotton are removed.
A definite restoration is placed. The patient is then recalled after 6
weeks when cold testing and symptoms are evaluated [54].
If bonded composite resin will be used immediately after
placement of MTA, The unset MTA should be overlaid with a thinprotective layer of resin modified glass monomer or flow able resin
before bonding procedure [55].

Pulp capping with adhesive resin was reported in manystudies [56-58]. However these studies revealed significant better
result, less pulp necrosis and thicker dentine bridge when calcium
hydroxide was used as direct capping agent.

Mode of action

At the site of exposure, primary odontoblasts together withother pulpal cells are destroyed and inflammation is initiated.
If infection/inflammation in coronal pulp is under control,
odontoblast-like cells will regenerate. Pulp capping materials
such as MTA and calcium hydroxide induce the release of growth
factor proteins and bio active molecules from dentin matrix. Postnatal stem cells in human dental pulp are capable of differentiating

into odontoblast-like cells upon receiving inductive signals frombioactive molecules and growth factor proteins. Reparative dentin
is formed from odontoblast-like cells and not from primaryodontoblasts as in case of indirect pulp capping [59].

Treatment outcome

For decade, calcium hydroxide-base materials have been thegold standard for direct pulp capping [60,61]. A retrospective study[62] reported success rate of direct pulp capping with calcium
hydroxide after 1 year (80.1%), 5 years (68%) and 9 years (58.7%).
In another the long term study [63], the success rate of pulp cappingwith calcium hydroxide is 76.3% after 13.3 years. These results
confirm that success rates using CH diminish over time, primarily
due to the dissolution of material under restorations and overdentinal bridges with tunnel defects [64]. An alternative to calcium
hydroxide-based capping materials is MTA, which was developedby Torabinejad and co-workers at Loma Linda University in the
1990s [65]. High success rate (97.9%) after capping with MTA incuriously exposed permanent teeth and all teeth showed continued
root formation [66].

In clinical assessment of carious permanent teeth capped with
MTA and followed for 6, 12, 18, 24 months, showed success rate(93%) with evidence of continued root growth [67]. Many casereports and clinical studies compared treatment outcome of MTA
and CH when used as direct pulp capping agents. In preliminary
study [68], 14 intact third maxillary molars teeth were cappedwith either CH or MTA. Histological examination of teeth showeddentinal bridge formation and mild chronic inflammation 2 months
after pulp capping with MTA. While with CH, irregular and thindentinal bridge was formed after 3 months with associated pulpal
necrosis, hyperemia and inflammation.
Another histological study [69] revealed that all teeth cappedwith MTA showed dentinal bridge formation. In contrast, only
60% of CH-capped pulps showed hard tissue formation. Also
MTA-capped pulps showed significantly thicker dentine bridge
than those capped with CH. These results are similar to findings
in another histological [70] that MTA-capped teeth were free frominflammation and showed dentine bridge formation within 3months, while CH-capped teeth showed less consistent formation of
Dentine Bridge that had numerous tunnel defects and persistence
inflammation up to 3 months after capping.
A recent study [71] showed MTA is more effective than CH
for maintaining long term pulp vitality after direct pulp capping.
A recent systematic review [72] for vital pulp therapy in vitalpermanent teeth with cariously exposed pulp revealed success rateof direct pulp capping was different depending on follow up time (>6months -1 year, 87.5%), (>1-2years, 95.4%), (>2-3 years, 87.7%)
and (>3 years, 72.9%). Also showed that direct comparisons ofweighed pooled success rate when using either CH or MTA as pulp
capping medication revealed no statistically significant difference,
while in indirect comparisons of weighted pooled success rate
showed that MTA was superior to calcium hydroxide in direct pulp
capping.

How to cite this article: Kareem A M K, Rasha M A. Managements of Immature Apex: a Review. Mod Res Dent. 1(1). MRD.000503. 2017.
DOI: 10.31031/MRD.2017.01.000503

11

Mod Res Dent

Modern Research in Dentistry
A recent retrospective study [55] aimed to evaluate successrate and treatment outcome of direct pulp capping in immature
permanent teeth and to investigate potential factors (age, sex, tooth
position, jaw, exposure site, capping material, temporary filling)
contributing to the pulpal survival according to time. This study
reveals survival rate (89.9%) after 1 year and (67.4%) after 3 years
when MTA was used as direct capping agent. CH yielded (73.9%)
and (52.5%) after 1 and 3 years respectively. Patients <40 years age
group had better survival rate than older ones, and when exposuresite was limited to occlusal site there was better survival than when
it was on axial side. Other potential factors not significantly affectsurvival rates.

Partial Pulpotomy

Partial Pulpotomy is defined as “The surgical removal ofcoronal portion of vital as a means of preserving the vitality of theremaining coronal and ridiculer pulp tissues” [18].

Indications [37]a.

Restorable permanent teeth.

b.
Deep Carious lesions or traumatic fractures longer than
24 hours with vital pulp exposure.
c.
When pulpal inflammation is expected to be greater thannormal and pulpal bleeding cannot be controlled within several
minutes.

d.
No symptoms of pulpits or with diagnosis of reversible
pulpits.

Technique (Figure 4)

The carious exposure generally occurs in the depth of a
carious excavation. The cavity preparation presents convenientand effective location for the protection and seal of the pulp withpulp capping material. On the other hand, a traumatic fracture
leaves the pulp exposed on the surface of the tooth and presents
a problem in both retention of capping material and preventionof leakage. In addition to time of exposure, health of pulp before
trauma, diameter of pulp exposure (1.5mm diameter is the critical),age of the tooth, no concomitant luxation injury and the stage ofroot development [73]. To address many of these challenges, Cvek
procedure [74] was developed. The tooth is anaesthetized andisolated with rubber dam. A 1-2mm deep cavity is prepared into
the pulp using sterile diamond bur of appropriate size at high speedwith copious coolant. If bleeding is excessive the pulp is excavateddeeper and cotton pellet moisture with 3-6% sodium hypochlorite
for 10-20 second is placed over the exposed pulp. Sodium hydroxide
serves as an excellent diagnostic tool to help to evaluate how far
the inflammation has progressed into the pulp. A profuse bleedingthat is difficult to stop indicates severe pulpal inflammation and thedecision to proceed with pulpotomy [75].

Figure 4: Partial pulpotomy in upper central incisor.
a)Preoperative radiograph shows traumatic pulp exposure.
b)
Partial pulpotomy capped with MTA.
c)
Postoperative radiograph shows complete root formation.

Any blood clot should be removed. If homeostasis is achieved,
hard setting calcium hydroxide is placed over pulpal tissue andsealed with permanent restoration [76] or MTA is mixed according
to the manufacturer’s instructions (3:1, powder to liquid), andplaced directly over exposed pulp tissue and surrounding dentinewith at least 1.5mm thickness [77]. Definitive restoration is either
placed over MTA several days later or placed immediately after
applying a layer flow able resin on unset MTA.

Mode of action

Similar to direct pulp capping, calcium hydroxide and mineral
trioxide aggregate induce dentine bridge formation most likely
by indirect mechanism through the release of growth factors
from dentine matrix. Growth factors proteins stimulate thedifferentiation of post-natal stem cells in human dental pulp into
odontoblasts-like cells that forms dentine bridge [59,78].

Treatment outcome

Studies have demonstrated that partial pulp capping of exposedpermanent teeth with calcium hydroxide is an alternative treatment
with good clinical outcome [79-81] and formation of reparative
dentine [82]. Recently, mineral trioxide aggregate has been usedsuccessfully as pulp capping material after partial pulpotomy [8385]. In a prospective clinical study [86], partial pulpotomy was
performed by grey MTA in 28 teeth with carious exposures. The
patients were followed for 24 months. 79% of these teeth had
normal response to vitality tests and with no radiographic evidenceof pathosis.

How to cite this article: Kareem A M K, Rasha M A. Managements of Immature Apex: a Review. Mod Res Dent. 1(1). MRD.000503. 2017.
DOI: 10.31031/MRD.2017.01.000503

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Mod Res Dent

Modern Research in Dentistry
In another prospective clinical and radiographic study [87],comparing CH and MTA as pulp capping materials after partial
pulpotomy in cariously exposed teeth, it was reported that no
significant differences in radiographic and clinical success rates
between CH (91%) and MTA (93%). Hard tissue barrier was
noticed under CH (55%) compared with (64%) under MTA. Long
term evaluation of partial pulpotomy was (93.9%) after 49 months[88]. In a recent randomized clinical trial [50] comparing direct
pulp capping and partial pulpotomy, showed no difference in pulp
vitality at one year using CH. A recent systematic review (72) forvital pulp therapy in vital permanent teeth with cariously exposed
pulp revealed success rate of partial pulpotomy was different

depending on follow up time (>6 months -1 year, 97.6%), (>1-2
years, 97.5%), (>2-3 years, 97.6%) and (>3 years, 99.4%). Also
showed that direct comparisons of weighed pooled success rate
when using either CH or MTA as pulp capping medication revealed
no statistically significant difference, while in indirect comparisonsof weighted pooled success rate showed that CH was superior to
MTA in partial pulpotomy.

Full Pulpotomy

Full pulpotomy is defined as “The removal of entire coronal
pulp to the level of the root canal orifice or as much as 2-3mm
apical to the orifices” [18].

Figure 5: Pulpotomy in lower molar.
a)Preoperative radiograph with extensive decay and open apex.
b)
After removal of caries and perform pulpotomy and resorted with amalgam.
c)Postoperative radiograph after periapical tissue healing and apex closure.

Indications [88]a.

Restorable permanent teeth.

b.
Deep Carious lesions or traumatic fractures longer than
72 hours with vital pulp exposure.
c.
When pulpal bleeding cannot be controlled within 10
minutes.

The main disadvantage of full pulpotomy is that pulp testing is
not possible due to the loss of coronal pulp tissue, so radiographic
follow up is extremely important.

Technique [88] (Figure 5)

Tooth is anaesthetized and isolated with rubber dam. The
coronal pulp is removed to the level of root canal orifices. If thereis bleeding, homeostasis is done by placing cotton pellet moisturewith 3-6% sodium hypochlorite for 10-20 seconds. If bleedingcannot be controlled, then decision for lumpectomy should betaken. Any blood clot should be removed. If homeostasis is achieved,
hard setting calcium hydroxide or MTA with bacterial tight seal andcoronal restoration are carried out as with partial pulpotomy.

Mode of action

In response to pulpal dressing with calcium hydroxide or
mineral trioxide aggregate apposition of hard tissue is achieved
similarly as direct pulp capping and partial pulpotomy. Dentine
bridge formation following apex genesis is a reparative process ofdentine-pulp complex. However, the continued root formation is anormal physiological process [23].

Treatment outcome

In a case report [89], pulpotomy showed successful resultin treatment of dens imagination in 2 mandible premolars.
In histological study [90], comparing CH and MTA pulpotomymaterials showed that teeth pulp-capped with MTA had significant
less inflammation and more homogenous and continuous dentine
bridge than those capped with CH. Another study [91] comparing
CH and MTA as capping materials for 30 immature permanent teeth(15 with CH and 15 with MTA) and followed for 3, 6, 12 months
showed that only 2 teeth that were capped with CH failed withassociation of pain and swelling. The authors recommend MTA asa suitable alternative to CH. Pulpotomy with MTA as pulp capping
material was performed on symptomatic teeth with history of
lingered pain [92] and histological observation showed complete
dentin formation 2 months after treatment to all the treated teeth
In another case series of pulpotomy with MTA as pulp capping
material was performed on teeth with irreversible pulpitis [93]and followed for 19.7 months showed that only 1 of 19 teeth had
persistence pain. Pulpotomy with CH as pulp capping material in
symptomatic teeth [94] or with periodical involvement [90-92]
showed complete resolution of symptoms, periodical healing andcontinued root formation. A recent systematic review [72] for vital
pulp therapy in vital permanent teeth with curiously exposed pulp
revealed success rate of full pulpotomy was different depending on

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Modern Research in Dentistryfollow up time (>6 months -1 year, 94%), (>1-2 years, 94.9%), (>23 years, 96.9%) and (>3 years, 99.3%). Also showed that direct andindirect comparisons of weighed pooled success rate when using
either CH or MTA as pulp capping medication revealed that MTA
was superior to CH in full pulpotomy.

Calcium Hydroxide Versus Mineral Trioxide Aggregate
in Vital Pulp Therapies
The biological reactions resulting from application of bioactive
materials to the pulp are confounded by several factors such as theformulation of applied material, concentration and rate of releaseof active ingredient, distance it has to diffuse in a chemically active
form to the target cells, status of dentine, presence of infection andthe health status of the pulp. It has been suggested that the type ofbiomaterial selected is of lesser consequence and that the qualityof the seal of the cavity to prevent microbial ingress is the mostimportant factor determining the success of the procedure [95].

Hard tissue induced by calcium hydroxide (Figure 6)

When CH is placed against the pulp, the high PH of CH resultsin zone of liquefaction necrosis subjacent to CH and a deeper zoneof coagulation necrosis next to vital pulp within the first week
(approximately 1.5mm combined width incase of non-setting CH)[96]. Dentine matrix appeared around 30 days later once the cellularand vascular inflammatory events began to fade. Growth factor

Mod Res Dent

proteins, bone morphogenic proteins and bioactive molecules are
released from dentin matrix and stimulate the differentiation of
pulpal stem cells into odontoblasts-like cells [95]. Collagen is laid
down approximating the necrotic zone and mineralized crystals
are deposited in the region. Thickening of barrier and appearanceof dentine-like tissue has been reported to be observed at around4 weeks after pulp capping procedure and then dentin deposition
begins [95].

Drawbacks of calcium hydroxide

Length of time for induction of coronal hard tissue that ranges
from 2-3 months [96]. Non adhesive nature of the cement andits dissolution over time may lead to micro leakage and entry ofbacteria to exposure site [97]. It is important to ensure seal by arestoration overlying the cement [71]. Bacterial contamination may
also occur through tunnel defects (imperfection in dentine bridge
due to inclusion of blood vessels) [64]. Impaction of particles of
capping agent, enclosing action of CH up to 1.5mm compromisingvascularity of the pulp and interference by blood clot are otherfactors responsible for failure of procedure Calcium hydroxide has
limited solubility and infusibility, its antimicrobial effect is limited
to superficial layers of pulp, thus CH may be successful only in casesof minimal inflammation. If inflammation is severe the procedure
generally fails [94].

Figure 6: Calcium hydroxide and pulpal responses.
a)Exposed pulp, b) The high PH generates a zone liquefaction necrosis and a zone of coagulation necrosis, c) Sperical fociof calcification are formed that coalesce to form calcification zone and next to that collagen is formed, d) Bone like tissue isdeposited containing cells and vascular inclusions.

Hard tissue induced by mineral trioxide aggregate(Figure 7)
When MTA is placed against the pulp, the high PH of MTA resultsin zone of coagulation necrosis next to vital pulp after one week. No
zone of liquefaction necrosis is formed subjacent to MTA. High PH
lasts for at least 8 weeks. Growth factor proteins, bone morphogenic
proteins and bioactive molecules stimulate the differentiationof pulpal stem cells into odontoblasts-like cells which produce
collagen matrix. A regular hard tissue barrier with cellar inclusion
was seen after 2 weeks [95]. The hard tissue barrier appears to beformed earlier than under CH, with larger daily dentin increments,

few vascular inclusions and with less inflammation [98]. MTA forms
a very tight seal where it contacts the dentin walls, most likely due toa chemical bond between MTA and dentin; a layer of hydroxyapatite
is created as a link [99]. This layer prevents and reduces bacterial
penetration to the pulp; enhance biocompatibility, sealing ability
and dentinogenic activity of MTA. This seal might be the main causeof successful performance of this material [100].

Drawbacks of mineral trioxide aggregate

Despite its many advantages, MTA has some drawbacks such as
discoloration potential, presence of toxic elements in the material

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Modern Research in Dentistrycomposition, difficult handling characteristics, long setting time,high material cost, an absence of a known solvent for this material
and the difficulty of its removal after curing [101].

Internal bleaching was reported to be the treatment of
discoloration due to MTA application in vital pulp therapy [102].
It should also be noted that the total amount of arsenic (that cancause toxicity) in all types of MTA is insignificant [103].

Figure 7: Mineral trioxide aggregate and pulpal responses.
a)High PH generates a very narrow zone of coagulation necrosis,b)
Next to that zone reparative dentinogenesis zone is formed.

Apexification

Technique (Figure 8)

Apexification is defined as “a method of inducing a calcified
barrier in a root with open apex or the continued apical developmentof incompletely formed root in teeth with necrotic pulp” [18].

The tooth should be isolated with rubber dam. The firstphase of treatment is to disinfect the root canal system to ensure
periodical healing [22]. The canal length is estimated with a parallel
preoperative radiograph, and after access to the canals is made, afile is placed to the determined length and the working length isconfirmed by radiograph. Very light filling with copious irrigation
using 0.5% sodium hypochlorite is performed. The canal is dried
with paper points and creamy mix of calcium hydroxide is placed
into the canal and sealed with temporary restoration for 1 to 4
weeks until there is no sign of infection [94].

Indications [37]a.

b.

Permanent teeth.

Non vital pulp with open apex and thin dentin walls.

c.
Standard instrumentation technique cannot create apicalstop.

Figure 8: Apeification with MTA as apical plug.
A)
The canal is disinfected with copious irrigation.
B)
Calcium phosphate is placed through the apex as a barrier.
C)
4mm of MTA is places at the apex.
D)
The canal is filled with thermoplastized gutta-percha.
E)
Bonded resin resorted is placed at level below CEJ.

Traditional apexification
Pure calcium hydroxide powder is mixed with sterile saline toa thick consistency. Ready-mixed commercial calcium hydroxide
can also be used [104]. The calcium hydroxide is packed against
the apical soft tissue with a plugged. This step is followed bybackfilling with calcium hydroxide to completely fill the canal. The
excess is removed from access cavity to level of the root orifices,
and a well-sealing temporary restoration. A radiograph is taken

in order to evaluate formation of hard tissue barrier and washoutof CH [94]. Controversy exists as to whether or how often the
calcium hydroxide should be changed. Several studies [105-107]
suggested placing the paste only once and waiting for radiographic
evidence of barrier formation, and that there was nothing gainedby repeated root filling either monthly or after 3 months. A recent
study [108] reported that apical barrier was formed in shorttime (30 weeks) due to the minimal disturbance of apical area by
avoiding repeated instrumentation and dressing changing. On the

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Modern Research in Dentistryother hand, a number of studies [109-112] suggested that regularreplacement of dressing allows clinical assessment of barrier
formation and may increase the speed of bridge formation. Thisis due to the solubility of CH when comes in contact with tissue
fluids [25]. Other investigators [113,114] suggested that calcium
hydroxide should be replaced only when symptoms develop or thematerial dissolves out of the canal when assessed radio graphically.
However, the size of foramen opening and stage of development
may be important factors to determine the time to replace thedressing [115]. Radiograph may not be a relevant to evaluate
calcium hydroxide washout; because the additives (barium
sulphate) that are responsible for CH radio-opacity do not washout
as readily as calcium hydroxide so that if they are present in thecanal, evaluation of washout is not possible [94]. When hard tissue
barrier is indicated on radiograph, the calcium hydroxide is washedout with sodium hypochlorite and apical barrier is detected gently
by a file or a paper point. The entire canal is then filled with thermo
plasticized gutter perch [94].

One step/visit apexification (Figure 8)

MTA can be used as apical plug or even as a root canal obscuration[116]. If MTA will be used, calcium sulphate is pushed through the
apex to provide a restorable extra ridiculer matrix against which
to pack the MTA [117]. Other types of matrix were also reported
as collagen matrix [118]. However, MTA can be placed without
matrix and care must be taken as MTA should be confined to root
canal end [119]. MTA should be mixed according to manufacturer’s
instructions to a thick creamy consistency and placed 1-1.5 mm
short of working length using a carrier and condensed with minimalpressure. This is repeated until approximately 5mm of material isdeposited apically [119]. Moist cotton is placed in the canal for atleast 6 hours and the entire canal is filled with thermo plasticized
gutter perch [120] or the root filling is placed immediately over
MTA because the tissue fluid of the open apex will probably provide
enough moisture for MTA to set [121].
Soften filling technique is indicated in these canals because theapical diameter is larger than the coronal diameter. Care must be
taken to avoid excessive lateral forces during obscuration technique[94]. It was reported that short term canal medication with calcium
hydroxide followed by an apical plug of MTA may increase themarginal adaptation of MTA and increase long-term prognosis forteeth with necrotic pulps and open apices [122,123]. Because theacidic environment due to inflammation can cause porosity in set
MTA and affect its sealing ability [124,125].

Mode of action

In apexification procedures, the infected necrotic is removed
up to the apex by means of mechanical debridement and antiseptic
chemical irrigation [23]. Accordingly it is unlikely that reparative
dentine can be formed because of the absence of pulp. The calcified
barrier at open apex has been described as cemented-like tissue
and asteroid-like tissue [126].

Calcium hydroxide and mineral trioxide aggregate stimulate
release of growth factors and bioactive molecules from cemented

matrix and signal progenitor/stem cells in periodontal ligament
to differentiate into cement oblast-like cells that forms cemented
tissue [127].
CH and MTA also stimulate release of growth factors andbioactive molecules from alveolar bone marrow matrix and signal
progenitor/stem cells in periodontal ligament and mesenchymal
stem cells in alveolar bone marrow to differentiate into osteoblasticlike cells that forms asteroid tissue [128].

It was shown that MTA offers a biological substrate forcement oblasts attachment and growth as well as production ofmineralized matrix gene (osteocalcin) and protein expression
over MTA [36]. Continued physiological root development ofimmature permanent tooth with infected necrotic pulps and apicalperiodontitis after apexification procedure treated with calcium
hydroxide was reported [24,129]. The newly formed root apical tothe hard tissue barrier had normal root structure with pulp tissue
in the canal space surrounded by dentine and cemented. It appears
in this case that apical papilla and her twig’s epithelial root sheath(HERS) have survived despite apical periodontitis. HERS cells arecapable of signaling stem cells in apical papilla to differentiate into
odontoblasts and produce root dentine [129].

Treatment outcome

In a clinical study [127], apexification performed with calcium
hydroxide in 34 teeth revealed that only 4 teeth failed to form
hard tissue barrier. In a large retrospective clinical study [128],328 located non-vital incisors were treated with CH and followed
for 4 years. This study showed periodical healing in 95% of teeth
and increased frequency of fracture from 77% in least developed
teeth to 28% in most developed roots. Two large clinical studies[129,130] involved treatment with CH and subsequent guttapercha filling have shown average healing rate 95%. In a review often studies [111], the use of CH for apical barrier formation was
successful in 74-100% of cases irrespective of the proprietarybrand used. Continued physiological root development ofimmature permanent tooth with infected necrotic pulps and apicalperiodontitis after apexification procedure treated with calcium
hydroxide was reported [24,129]. The newly formed root apicalto the hard tissue barrier had normal root structure with pulp
tissue in the canal space surrounded by dentine and cemented.
In another retrospective study [130], 23 necrotic immature teeth
treated for either long term with CH (n=16) or short term with MTA(n=7). All necrotic immature teeth achieved a nearly normal root
development after (mean 16 months). In a case series study [131],a successful outcome in 10 of 11 teeth with necrotic pulps and open
apices after application of MTA was observed and apical barrier
formation after 24 months. Two studies [132,121] of necrotic pulps
and open apices treated either with white MTA or grey MTA as
apical barriers, radiographic examination revealed 81% success forthese cases.
In another case series study [133], used MTA as apical plugin 17 incisors and followed for 12.53 months showed that 94.1%
were assessed as being successful clinically, whereas 76.5% were

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16Modern Research in Dentistry
reported to be successful radio graphically. In a large retrospective
clinical investigation [134] on teeth with necrotic pulps and open
apices that were treated with MTA as apical plug comparing 1 visit
with 2 visits procedures, showed no significant difference between
the two treatment protocols. A recent clinical and radiographic
assessment [135] of two types of White MTA used as apical plug
after initial dressing with CH showed overall success rate 95.5%
after 23.4 months follow up.
Another recent cohort study [136] assessing outcome oftreatment of open apices with orthograde placement of MTA apicalplug, reported that teeth with and without preoperative periodical
radiolucencies showed healed rates of 85% and 96% respectively
after 4 years follow up. In a comparative study [137] on permanent
maxillary incisors with CH or MTA, demonstrated that mean time
for CH (7 months) to form hard tissue barrier is significantly longer
than time needed by MTA (3 months) to induce similar barrier.
Another investigation [138] compared MTA with CH for treatmentof teeth with immature roots and observed for 12 months. Noneof MTA cases showed signs of clinical and radiographic failure,
whereas 2 of 15 teeth in CH group had tenderness to percussion
and persistent periodical inflammation.

In a report of three cases [137] describing treatment outcomeof unintended extrusion of MTA into periodical tissue during apicalbarrier treatment showed that only in one case after 4 years follow
up MTA had resorted and periodical lesion had healed while in twoother cases the patient remained symptomatic and scheduled for
periodical surgery. Another two studies [138,139] revealed thatcomplete periodical healing is possible despite extrusion of MTA
periodically.
A meta-analysis [139] of 30 article published in recent years
indicated that MTA has high clinical success rate, provides best seal,shows superior biocompatibility, and the only root end filling whencompared with amalgam, IRM, super EBA. A recent systematic
review and meta analysis [140] comparing MTA and CH as apical

Mod Res Dent

barriers used in apexification of immature permanent teeth showedthat regarding clinical success and apical barrier formation, either
CH or MTA may be used for apexification of immature teeth.

Calcium Hydroxide Versus Mineral Trioxide Aggregate
in Non-Vital Pulp Therapies

Apexification technique first requires elimination of bacterial
infection from root canal and prevention of re-infection of thisspace [22]. Disinfection of the root canal space is straight forward
for most cases; however, there is no natural apical construction orstop against which a suitable root filling material can be placed toprevent re-infection of this space [20]. Therefore one of the aimsof treatment is to produce apical barrier against which a root
canal filling can be placed and prevent extrusion of material into
surrounding tissue. Studies vary in assessment of time required
for apical formation in apexification using calcium hydroxide. In areview of ten studies [111], reported an average for apical barrier
formation ranging from 5-20 months. In another study [118] of
44 non-vital teeth undergoing CH apexification, found that themean time to barrier formation was ranging from 4-16 months.
The strongest predictor of rapid barrier formation was the rate ofchange of calcium hydroxide and also the narrower initial apical
width the faster apical barrier formation.

It was reported that the infection or the presence of periodical
radiolucency at the start of treatment increases the time requiredfor barrier formation [141]. However, other studies [130,142]
refuted this finding and stated that there is no relation between
preoperative infection or radiolucency and rate of formation of
apical barrier. It was found [143] that in the presence of symptoms,
the time required for apical closure was extended by approximately
5 months to an average of 15.9 months.
comparative study [137] on permanent maxillary incisors withCH or MTA, demonstrated that mean time for CH (7 months) toform hard tissue barrier is significantly longer than time needed by
MTA (3 months) to induce similar barrier.

Figure 9: Calcium hydroxide and periapical changes.
a)Infected pulp and inflammation.
b)
The high PH generates a zone liquefaction necrosis and a zone of coagulation necrosis.
c)
New hard tissue forming cells from periapical tissue and formation of cementoid and osetoid tissue.
d)Root filling with gutta-percha, notice vascular inclusion within hard apical barrier.

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Modern Research in Dentistry
Hard tissue induced by calcium hydroxide (Figure 9)
When CH is placed against periodical tissues, the high PH valueof CH results in zone of liquefaction necrosis subjacent to CH and a
deeper zone of coagulation necrosis next to periodical tissues [103].
This coagulation necrosis zone stimulates release of growth factors(wound healing signals) and bioactive molecules from cemented
matrix and alveolar bone marrow matrix. The response to thesefactors appear to be recruitment of new hard tissue forming fromapical tissue, these are usually of cementoblastic but may also be
osteoblastic origin [144]. During this process numerous vascularinclusions may occur [144].

Drawbacks of calcium hydroxide

Length of time for induction of apical hard that ranges from
6-18 months [111,118]. Such lengths of time may delay completionof treatment and failure to comply the patient. Incomplete apical
hard tissue barrier occurs due to vascular inclusions and may allow
bacterial invasion through these defects [144].

Long term calcium hydroxide dressing cause changes inphysical structure of dentine [145,146]. Such changes may weaken
the dentine and lead to root fractures [128,147,148]. However,in a recent systematic review [149] of the effect of non-setting
calcium hydroxide and mechanical properties of dentine showedthat there are no clinical trials examining the relation between
calcium hydroxide intra canal dressing and root fracture. However,
the majority of in vitro studies showed reduction in mechanicalproperties of ridiculer dentine after exposure to CH for 5 weeks orlonger.

Hard tissue induced by mineral trioxide aggregate(Figure 10)

When MTA is placed against periodical tissues, the high PH
value of MTA results in very narrow zone of coagulation necrosis
next to periodical tissues [103]. MTA modulates cytokines
production and encourages differentiation and migration of hardtissue producing cells, whereby hydroxyapatite is formed on MTA
surface and biological seal is created [108].

Figure 10: Mineral trioxide aggregate and pulpal responses.
a)
MTA induce release of wound healing signals.
b)High PH generates a very narrow zone of coagulation necrosis.
c)
Next to that zone reparative dentinogenesis zone is formed.

Drawbacks of mineral trioxide aggregate

Glass monomer cements as root strengthening material

MTA has some drawbacks such as difficult handlingcharacteristics, long setting time [108]. The porosity in set MTA
has been identified as potential drawback for the material. It canallow potential penetration of bacteria or by-products. However,studies [150,151] have shown after MTA placement, a layer ofhydroxyapatite forms over the material that fills the voids andsurface defects.

Glass monomer cements have been shown to have long termadhesion effects by bonding to the hydroxyapatite component ofdentine [154].

Reinforcement of Thin Dentinal Walls

Root strengthening interventions can be divided into
the following four categories [152]. Adhesive resins as root
strengthening material the use of adhesive sealers in the root canalsystem might possibly enhance resistance to fracture of thin weak
dentinal walls as in immature permanent teeth [153].

Intra-canal composite resin as strengthening root
material

The use of newer dentine bonding techniques has been shownto strengthen the thin dentine walls of immature teeth [155].
Greater resistance to root fracture after placement of 4mm thickapical plug of MTA followed by intra-canal composite resin whencompared with MTA followed by gutta-percha and sealer was
reported [156]. Before placement of composite, the internal dentine
walls of canal are acid etched and dentine bonding agent is applied
to the walls. 2mm increment of condensable light cure composite

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resin is placed in the canal and cured. This step is repeated until
the canal and access opening are obliterated [157]. However, due toincomplete polymerization in deeper depths of the canal becauseof limited transmission of light through the material, clear plastic
posts have been developed to allow light transmission throughout
the canal and cure entire mass of composite [158]. Resin modified
glass monomer with translucent curing post showed significant
increased resistance to root fracture when compared with gutter-perch alone in open apex [159].

Fiber glass posts

Fiber-reinforced composite posts have been reported to havebiomechanical properties close to those of dentine [160] andsimilar modulus of elasticity to that of dentine [161]. This seems to
reduce stress transmission to the root canal walls by the post andthus avoiding possible root fracture [162,163].

Revitalization treatment

Revitalization is a new treatment procedure that may replace
apexification procedures. Is defined as “The attempts to revivetissues in the pulp space and continue root formation in immature
teeth with non-vital pulp” [164]. In this treatment, the ideal goal
is to prepare an appropriate environment inside the root canal
space (i.e., absence of bacteria and necrotic pulp tissue, presenceof a scaffold and a tight coronal seal) that promotes repopulationof these stem cells, regeneration of pulp tissue, and continuation ofroot development [165].

Indications and recommendations [166]

The traumatized tooth must be non-vital and not be suitable
for apex genesis, apexification, partial pulpotomy, or root canal

obscuration treatments. The tooth must be permanent andimmature with open apex that is wide to a diameter of 1.1mm orlarger and exposed pulp. The patient must be aged 7-16 years,
in good health and have parent’s guardians willing to take themto attend multiple appointments. Antibiotic paste can be used asadditional disinfectant to sodium hydroxide and the patient needs
to be warned about the potential for discoloration. An anesthetic
without a vasoconstrictor should be used when attempting to
induce bleeding into the root canal. A thin layer of white MTA
or calcium hydroxide should be placed over the blood clot. An
endodontic sealer is not compatible and cannot be used. The toothshould be restored with resin modified glass monomer to help
prevent micro leakage.

Technique (Figure 11)

Several case reports and case series have recently introduced
detailed regenerative endodontic techniques applied to casesof necrotic immature permanent teeth [167-170]. The toothis anesthetized and isolated with rubber dam. The canal isdisinfected without mechanical instrumentation but with copious
irrigation with 2.5% sodium hypochlorite. After drying the canal,
tri-antibiotic paste, sometimes called Hoshino’s paste [171].
The paste contains 200mg ciprofloxacin, 500mg metronidazole,and 100mg minocycline. The triple antibiotic paste is placed incontact with necrotic pulp inside the root canal for up to 1 month
before revascularization procedure. After one month, antibiotic isremoved from canal by irrigation with 2.5% sodium hypochlorite
and 17% ethylene diamine-tetracetic acid. Conditioning the dentin
surface with ethylene diaminetetra acetic acid may enhance theadherence and differentiation of dental pulp stem cells during pulp
regeneration [172,173].

Figure 11: Revitalization procedure.
a)Preoperative radiograph with periapical lesion and open apex.
b)
After 3 months elongation with periapical lesion and open apex.
c)
After 8 months shows narrowing if apex and thickening of dentine walls.
d)
After 18 months shows healing of lesion and apical closure.

Bleeding is induced till the level of canal orifice by passing afile beyond working length and causing irritation in periodical
tissue. The bleeding is left for 15 minutes so that the blood would
clot. Blood clot serves as a protein scaffold and permitting threedimensional in growth of tissue. MTA is placed over blood clot
followed by moist cotton and well-sealed temporary restoration.

After few days the cotton is removed and bonded restoration isplaced over set MTA.
Patient should be recalled every 6 month for clinical andradiographic examination to ensure thickening of dentine walls andcontinued root formation. Staining of the dentin by minocycline,
a derivative of tetracycline, has been reported. Therefore, some

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Modern Research in Dentistry

authors suggest eliminating the minocycline and keeping only
metronidazole and ciprofloxacin in the antibiotic paste (binate)[174]. While others suggest that sealing dentinal tubules withdentine bonding agent may reduce the intensity of discoloration
but did not prevent it [175-177].
Calcium hydroxide paste is another intracranial medicamentthat has been used to disinfect the canal before inducing bleeding[178,179]. However CH may not be suitable if there is remaining
vital pulp tissue in the canal. The direct contact of CH paste withtissue will induce formation of layer of calcified tissue which may
occlude the pulp space [180]. Another concern is that CH may
damage her twig’s epithelial root sheath and thereby destroy its
ability to induce the nearby undifferentiated cells into odontoblasts[181].
Another technique was reported [181,182], without inducing
intracranial bleeding and all cases showed noticeable apicalmaturation with increased root length but a significant narrowingof canal space.

Mode of action

The precise nature of hard tissue formed inside the canal spaceand continued root development of immature permanent teeth
with apical periodontitis/abscess following revascularization
procedures in humans is not known, because no histological studies
are available. It has been assumed that periodontal ligament tissue
might grow into the canal space and deposit cemented on the canalwalls after revascularization procedures [181]. HERS cells play anessential role in root development. If HERS cells survived in apicalperiodontitis/abscess after revascularization procedures, they
can signal progenitor/stem cells in the periodontal ligament todifferentiate into cement oblast-like cells and produce cementedlike tissue to promote root development [143]. If the apical papillaalso survived in apical periodontitis/abscess after revascularization
procedures, HERS cells will signal apical papilla cells to differentiate
into root primary odontoblasts and promote root dentine formation[183]. Thus, the incompletely formed root will continue its normal
physiological development after revascularization procedures.
However, no pulp-like tissue or dentine formation was present
in the apical portion of the canal space of immature teeth with apicalperiodontitis/abscess after revascularization procedures in animalstudies [184]. This indicates that the apical papilla did not survive.
Continued root development was evidenced by apical depositionof cemented without dentin after revascularization proceduresin animal studies, probably because HERS cells survived in apicalperiodontitis [185].
When the canal dentine was treated with 17% ethylene
diaminetetra acetic acid (EDTA) to expose dentine matrix, dentinassociated mineralized tissue appeared to be tightly attached to thecanal dentine walls, In addition, EDTA may also cause the release of
bioactive growth factors from dentine matrix [183]. If the tissues
present inside the canal space in human immature permanent
teeth with apical periodontitis/abscess after revascularization

procedures are similar to that observed in animals, thenrevascularization is a reparative process with the loss of pulp
biological function. Cemented and asteroid tissues are not normallypresent as part of the pulp tissue. These tissues inside the canal
space may function like periodontal tissues [186]. Histologicalstudies are necessary to verify whether repair or regenerationof the pulp tissue occurs inside the root canal space following
revascularization procedures in humans.

In immature permanent teeth with a long-standing apicalperiodontitis/abscess in adult patients, the apical papillae and
HERS cells may be severely damaged, thus hindering the potentialof continued root development. Furthermore, the functionality ofstem cells is age-related decline owing to change in the intrinsic
factors of stem cells and diminished signals within the extrinsic
local and systemic environment that modulate the function of stem
cells or their progeny [23].

The incompletely developed roots of immature permanent
teeth with infected necrotic pulp and apical periodontitis are not
attributable to the destruction of previously formed roots but are
attributable to the inhibition or damage of HERS cells. Therefore,
continued root development of human immature permanent teeth
with infected necrotic pulp and apical periodontitis/abscess afterrevascularization procedures does not appear to be a regenerative
process. It could be considered a physiological process if both apical
papilla and HERS survive in apical periodontitis/abscess after
periodical wound healing [23]. Regeneration of the dentine-pulp
complex after complete pulp necrosis or irreversible pulpitis withapical periodontitis is likely to occur only by tissue engineering[187] or gene therapy [188].

Treatment outcome

Most of evidence for revascularization procedures involves
successful case reports and case series [178,180,181]. The useof triple antibiotic paste was reported [182] to be effective fordisinfection of infected root canals, setting the conditions for
subsequent revascularization and showed healing of sinus tract[189]. A few cases have reported positive response to cold/EPT
after revascularization procedures [179,184,189,190]. However
it was found that both the coronal level of regenerated tissue andthe thickness of filling materials placed over this tissue affect thepresence or absence of responses to EPT and cold. The authors
reported positive responses to both EPT and cold in an immature
maxillary premolar with a coronal MTA plug placed close to thecement enamel level [190]. Cases treated with calcium hydroxide
paste as intracranial medicament to disinfect the canal before
inducing bleeding showed continued root development andthickening of dentin walls [188,189].

In a recent case report [191] of revascularization treatment
outcome of 2 immature necrotic mandible first molars withsymptomatic apical periodontitis and chronic apical abscess,respectively. In both teeth, the root canals received 3-weekdisinfection with the triple antibiotic paste. After 18 and 15
months (cases 1 and 2, respectively), the teeth showed advanced

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Modern Research in Dentistryroot development, thickening of the root walls, and complete
periradicular healing. In a recent study [192] reporting long term
outcome of three cases with necrotic immature teeth and followed
for 24, 48 and 42 months showed that all of the revascularized teeth
showed satisfactory clinical and radio graphical performances atlong-term follow-ups. In well-selected cases, the revascularization
technique may be a trustworthy alternative to conventional apex
genesis or apexification. A recent study [193] examining the effectof different irritant on the survival of human stem cells of the apical
papilla showed that the irrigation protocols evaluated in this study
that contained EDTA promoted SCAP survival, whereas protocols
in which 2% CHX was used appeared cytotoxic with no viable cells.

Also showed that chelating effect of EDTA promotes therelease of dentin-derived growth factors that were previously
embedded into dentin during the process of dentin genesis. These
growth factors have been shown to foster proliferation, survival,and differentiation of dental stem cells. A recent in vitro study[194] examining the effect of medications used in regeneration
techniques on chemical structure of immature human ridiculer
dentine showed that long-term exposure of ridiculer dentin to
Ca(OH)2 or antibiotic pastes might negatively affect the mechanicalproperties of dentin and increase the susceptibility to root fracture
because of either collagen degradation in the case of Ca(OH)2 or
excessive demineralization in the case of antibiotic pastes.
The null hypothesis that the 3 intracranial medicaments(triantibiotic, biantibiotic pastes and calcium hydroxide) haveno significant effect on the chemical structure of reticular dentin
was rejected. A retrospective evaluation [195] of radiographic
outcomes discovered that regenerative endodontic treatment withtriple antibiotic dressing increased root wall thickness significantly
more than either calcium hydroxide or form cresol. In addition, thisstudy revealed that in cases disinfected with calcium hydroxide, theradiographic location of calcium hydroxide inside the root canal
space influenced the root development. When calcium hydroxide
was radio graphically limited to coronal half of the root canal space,
the increase in root wall thickness was greater than when it wasplaced beyond coronal half.

Drawbacks of revitalization

There are several drawbacks and unfavorable outcomes ofregeneration procedure [196].

Discoloration

A study [185] demonstrated that the main reason for tooth
discoloration after treatment was the contact of minocycline in the
triple antibiotic paste with coronal dentinal walls during treatment
procedure. A recent study [187] suggested sealing dentinal wallsof the access cavity by using dentin bonding agent and composite
resin before placement of triple antibiotic paste inside the canal.
A practical way to prevent discoloration is replacing minocyclinewith an antibiotic that does not stain teeth. It was reported [197]that successful regenerative endodontic treatment of a maxillary
central incisor by using cofactor instead of minocycline in the

antibiotic mixture. Another two studies [192,198] introduced novel
method to shorten the treatment period and also prevent tooth
discoloration by omitting the intracranial medication process.

Treatment period

The required time for disinfection of the root canal spacewith triple antibiotic paste or calcium hydroxide and increased
number of clinical sessions (compared with one-visit MTA apicalbarrier technique) are other drawbacks of regenerative endodontic
treatment. The time spent on antibiotic disinfection in clinicalstudies varies between one [199] to eleven weeks [200].

Poor root development

Ideal root development pattern in immature teeth includes
increase in root length, increase in root wall thickness, andformation of the root apex. In some studies, the outcome ofregenerative endodontic treatments of necrotic immature teeth
was lower than ideal, including absence of increase in root length[184,201], absence of increase in root wall thickness [184,202], orlack of formation of tooth apex [202]. Formation of a hard-tissue
barrier inside the canal between the coronal MTA plug and the root
apex is another reported unfavorable outcome [202].
A recent study [202] revealed that root development potentialof immature necrotic teeth is related to the vitality of her twig
epithelial root sheath. Therefore, there might be a correlation
between dental history and quality of root development; thelonger the duration of pulp necrosis, the lower the quality of root
development after regenerative endodontic treatments.

Insufficient bleeding

A recent study [203] revealed that mesenchymal stem cells aredelivered into root canal space after bleeding induction in humanteeth, a phenomenon that did not happen in the absence of bloodclot inside the disinfected root canal space. An animal study [204]demonstrated that root canals that had a blood clot formation insidethem after disinfection had better radiographic outcome comparedwith those without blood clot. To facilitate bleeding after root canaldisinfection, using local anesthetics without vasoconstrictors is
recommended [184]. However, lack of bleeding or insufficient
bleeding after using plain local anesthetics is reported [184,205].
On the other hand, several cases with sufficient bleeding and lack ofroot development have been reported [184,206,207]. In addition,
there are several reports [174,191,192] of successful regenerative
endodontic treatment and continued root development without
bleeding induction.

Root canal calcification

Root canal calcification/obliteration is another problem after
regenerative endodontic treatment of necrotic immature teeth
that is reported in cases disinfected by calcium hydroxide [208212]. On the other hand, there is no report of complete root canal
calcification/ obliteration in cases disinfected by triple antibiotic
paste.

How to cite this article: Kareem A M K, Rasha M A. Managements of Immature Apex: a Review. Mod Res Dent. 1(1). MRD.000503. 2017.
DOI: 10.31031/MRD.2017.01.000503

21

Modern Research in Dentistry

References
1. Pashley DH, Liewehr FR, Cohen S, Burns RC (2006) Structure andfunction of dentin-pulp complex. Pathway of the pulp, (9th edn), St Louis,
Mosby, USA, p. 465.
2. Holland GR, Trowbridge HO, Rafter M, Torbinejad M, Walton RE, et al.
(2009) Protecting the pulp, preserving the apex. Endodontics, principles
and practice, (4th edn), Philadelphia, USA, pp. 26-34.

3. Kim S, Trowbridge H, Suda H, Cohen S, Burns RC, et al. (2002) Pulpal
reactions to caries and dental procedures. Pathway of the pulp, (8th edn),
St Louis, Mosby, USA, p. 573.

4. Reeves R, Stanley HR (1966) The relationship of bacterial penetrationand pulpal pathosis in carious tooth. Oral Surg Oral Med Oral Pathol
22(1): 59-65.
5. Thomas MS, Kundabala M (2012) Pulp hyperthermia during toothpreparation, the effect of rotary instrument, lasers, ultrasonic device
and airborne particles abrasion. J Calif Dent Assoc 40(9): 720-731.

6. Mjör IA, Ferrari M (2002) Pulp-dentin biology in restorative dentistry.
Part 6: Reactions to restorative material, tooth-restoration interface andadhesive techniques. Quintessence Int 33(1): 35-63.
7. Robertson A, Andreasen FM, Andreasen JO, Noren JG (2000) Long term
prognosis of crown-fractured permanent incisors. The effect of stage ofroot development and associated luxation injuries. Int paediatr Dent
10(3): 191-199.

8. Rosenberg PA, Schindler WG, Krell KV, Hicks ML, Davis SB, et al. (2009)
Identify the endodontic treatment modalities. J Endod 35(12): 16751694.
9. Brandt K, Kortegaard U, Poulsen S (1988) Longitudinal study ofelectrometric sensitivity of young permanent incisors. Scand J Dent Res
96(4): 334-338.

10. Pileggi R, Dumsha TC, Myslinksi NR (1996) The reliability of electric
pulp tests after concussion injury. Endodon Dent Traumatol 12(1): 1619.
11. Jafarzadeh H (2009) Lasser Doppler floemetry in endodontics. A review.
Int Endod J 42(6): 476-490.

12. Setzer FC, Kataoka SH, Natrielli F, Gondim-junior E, Caldeira CL, etal. (2012) Clinical diagnosis of pulp inflammation based on pulp
oxygenation rates measured by pulse oximetry. J Endod 38(7): 880-883.
13. Patel S (2009) New dimension in endodontic imaging: Part 2. Cone beam
computed tomography. Int Endod J 42(6): 462-475.

14. Souza RA, Gomes SC, Dantas Jda C, Silva-Sousa YT, Pecora JD, et al. (2004)
Importance Of diagnosis in the pulpotomy of immature permanent
teeth. Braz Dent J 18(3): 244-247.

15. Camp JH (2008) Diagnosis dilemmas in vital pulp therapy: treatment for
the toothache is changing, especially in young immature teeth. Pediatr
Dent 30(3): 197-205.

16. Mejare IA, Axelsson S, Davidson T, Frish F, Hakeberg M, et al. (2012)
Diagnosis of the condition of the dental pulp, A systematic review. Int
Endod J 45(7): 597-613.
17. Abu-Tahun I, Torabinejad (2012) Management of teeth with vital pulps
and open apices. Endo Topics 23: 79-104.

18. Panuroot A, Pairoj L (2011) Vital pulp therapy in vital permanent teeth
with cariously exposed pulp, a systematic review. J Endod 37(5): 581587.

19. Glickman GN, Bakland LK, Fouad AF, Hargreaves KM, Schwatrz SA, etal. (2009) Diagnostic terminology, report of an online survey. J Endod35(12): 1625-1633.

20. Cho SY, Seo DG, Lee SJ, Lee J, Lee SJ, et al. (2013) Prognostic factors forclinical outcome according to time after pulp direct pulp capping: J
Endod 39(3): 327-331.

Mod Res Dent

21. Bakland LK, Andreasen JO, Andreasen FM, Andreasen L (2007) New
Endodontic procedures using mineral trioxide aggregate for teeth withtraumatic injuries. Textbook and color Atlas of traumatic injuries toteeth. (4th edn), Ames, Lowa. Blackwell Munksgaard, USA, pp. 658-668.
22. Mass E, Zilberman U (2011) Long term radiographic pulp evaluation
after partial pulpotomy in young permanent molars. Quintessence Int
42(7): 547-554.

23. Teixeira LS, Demarco FF, Coppola MC, Bonow ML (2001) Clinical andradiographic evaluation of pulpotomies performed under intrapulpal
injection of anesthetic solution. Int Endod J 34(6): 440-446.
24. Caliskan MK (1993) Success of pulpotomy in the management ofhyperplastic pulpitis. Int Endod J 26(2): 142-148.

25. Torebinajad M, Chivian N (1999) Clinical applications of mineral trioxideaggregate. J Endod 25(3): 197-205.

26. Trowbridge HO, Hargreaves KM, Goodis HF (2002) Histology of pulpal
inflammation. Seltzer and Bender’s dental pulp. (3rd edn), Coral stream,
IL. Quintesense Publishing Co Inc. USA, pp. 227-245.
27. Caliskan MK (1995) Pulpotomy of carious vital teeth with periapicalinvolvement. Int Endod J 28(3): 172-176.

28. (2003) American Association of Endodontists, Glossary of endodontic
terms, (7th edn), Chicago, USA.
29. Webber RT (1984) Apexogenesis versus apexification. Dent Clin N Am
28(4): 669-697.

30. Shah N, Logani A, Bhaskar U (2008) Efficacy of revascularization to
induce apexification/apexogenesis in infected, nonvital, immature teeth:
A Pilot clinical study. J Endod 34(8): 919-925.
31. Morse DR, Larnie J, Yesilsoy C (1990) Apexification, review of theliterature. Quintessence Int 21(7): 589-596.
32. Rafter M (2005) Apexification: a review. Dent Traumatol 21(1): 1-8.

33. Lin LM, Rosenberg PA (2011) Repair and regeneration in endodontics.
Int Endod J 44(10): 889-906.
34. Fatma B, Nekoofar MH, Gungy M, Paul M (2013) The effect of various
mixing and placement techniques on compressive strength of mineral
trioxide aggregate. J Endod 39(1): 111-114.
35. Yang SF, Yang ZP, Change KW (1990) Continuing root formation following
apexification treatment. Dent Traumatology 6(5): 232-235.

36. Mohammadi Z, Dumme PMH (2011) Properties and applications ofcalcium hydroxide in endodontics and dental traumatology. Int EndodJ 44(8): 697-730.
37. Siqueira JF, Lopes HP (1999) Mechanism of antimicrobial activity ofcalcium hydroxide, a critical review. Int Endod J 32(5): 361-369.
38. Estrela C, Sydney GB, Bammann LL, Felippe O (1995) Mechanism ofaction of calcium and hydroxyl ions of calcium hydroxide on tissue andbacteria. Braz Dent J 6(2): 85-90.
39. Pisanti S, Sciaky I (1964) Origin of calcium in the repair wall after pulp
exposure in the dog. J Dent Res 43: 641-644.

40. Farhad A, Mohammadi Z (2005) Calcium hydroxide, a review. Int Dent J
55(5): 293-301.

41. Kratchman SI (2004) Perforation repair and one step apexification
procedure. Dent Clin N Am 48(1): 291-307.

42. Camilleri J, Montesin FE, Brady K, Sweeney R, Curtis RV, et al. (2005) The
constitution of mineral trioxide aggregate. Dent Mater 21(4): 297-303.
43. Torabinejad M, Watson TF, Pitt Ford TR (1993) Sealing ability of amineral trioxide aggregate when used as a root end filling material. J
Endod 19(12): 591-595.
44. Torabinejad M, Hong CU, McDonald F, Pitt Ford TR (1995) Physical andchemical properties of a new filling material. J Endod 21(7): 349-353.

How to cite this article: Kareem A M K, Rasha M A. Managements of Immature Apex: a Review. Mod Res Dent. 1(1). MRD.000503. 2017.
DOI: 10.31031/MRD.2017.01.000503

22Modern Research in Dentistry
45. Fridland M, Rosado R (2003) MTA solubility and porosity with different
water to powder ratios. J Endod 29(12): 814-817.

46. Torabinejad M, Masoud P (2010) Mineral trioxide aggregate, acomprehensive review, Part I: Chemical, physical and antibacterial
properties. J Endod 36(1): 16-27.

47. Maedi H, Nakano T, Tomokiyo A, Fujii S, Wada N, et al. (2010) Mineral
trioxide aggregate induces bone morphogenetic protein-2 expression
and calcification in human periodontal ligament cells. J Endod 36(4):647-652.
48. (2009) American Academy of Pediatric Dentistry Clinical Affairs
Committee, Pulp Therapy Subcommittee: Guideline on pulp therapy forprimary and immature permanent teeth. Pediatr Dent 31: 179-186.
49. Bogen G, Chandler NP (2012) Pulp preservation in immature permanent
teeth. Endod Topic 23: 131-152.

50. Bjørndal L, Larsen T, Thylstrup A (1997) A clinical and microbiologicalstudy of deep caries lesions during stepwise excavation using long
treatment intervals. Caries Res 31(6): 411-417.
51. Mertz-Fairhurst EJ, Curtis JR, Ergle JW, Reuggeberg FA, Adair S, et al.
(1998) Ultraconservative and cariostatic sealed restoration, results atyear 10. J Am Dent Ass 129(1): 55-66.

52. James L, Paul E (2011) Problem solving in endodontics: Problem solving
challenges in dentin hypersensitivity and vital pulp therapy, (5th edn),
Elsevier, Mosby, USA, p. 139.
53. Reeves S, Stanley HR (1966) The relationship of bacterial penetrationand pulpal pathosis in caries teeth. Oral Surg Oral Med Oral Path 22: 5260.
54. Tziafas D (2004) The future role of molecular approach to pulp-dentinal
regeneration. Caries Res 38(3): 314-320.

55. Smith AJ, Cassidy N, Perry H (1995) Reactionary dentinogenesis. Int J
Develo Bio 39(1): 273-280.
56. Gruythuysen RJ, van Strijp AJ, Wu MK (2010) Long term survival of in
direct pulp treatment performed in primary and permanent teeth withclinically diagnosed deep caries lesion. J Endod 36(9): 1490-1493.
57. Bjørndal L (2008) Indirect pulp therapy and stepwise excavation. J
Endod 34(7): S29-S33.

58. Thomson V, Craig RG, Curro FA (2008) Treatment of deep caries lesions
by complete excavation or partial removal, a critical review. J Am Dent
Ass 139(6): 705-712.
59. Miyashita H, Worthington HV, Qualtrough A (2007) Pulp management
for caries in adults, maintaining pulp vitality. Cochrane Database Sys Rev(2): CDOO4484.

60. Ricketts DNJ, Kidd EAM, Innes N (2006) Complete or ultraconservative
removal of decayed tissue in unfilled teeth. Cochrane Database Sys Rev(3): CDOO3808.

61. Bjørndal L, Reit C, Bruun G, Markvart M, Kjaeldguaard M, et al. (2010)
Treatment of deep caries lesion in adults, randomized clinical trial
comparing stepwise vs. direct complete excavation, and direct pulp
capping vs. partial pulpotomy. Eur J Oral Sci 118(3): 290-297.

62. Matsuo T, Nakanshi T, Shimizu H, Ebisu S (1996) A clinical study of direct
pulp capping applied to carious exposed pulps. J Endod 22(10): 551-556.
63. Silva AF, Tarquinii SBC, Demarco FF, Piva E, Rivero ERC, et al. (2006) The
influence of haemostatic agents on healing of healthy human dental pulp
tissue capped with calcium hydroxide. Int Endod J 39(4): 309-316.
64. Auschill TM, Arweiler NB, Hellwig E, Zamani-Alaei A, Sculean A, et al.
(2003) Success rate of direct pulp capping with calcium hydroxide.
Swcheiz Monatsschr Zahnmed 113(9): 946-952.

65. Bogen G, Chandler N, Ingle JI, Bakland LK, Baumgartner JC (2008)
Vital pulp therapy, Ingle’s endodontics, (6th edn), Hamilton, BC Decker,
Ontario, pp. 1310-1329.

Mod Res Dent

66. Elias RV, Dermaco FF, Tarquinio SB, Piva E (2007) Pulp response to theapplication of a self etching adhesive in human pulps after controlling
bleeding with sodium hypochlorite. Quintessence Int 38(2): 67-77.
67. Accorinti Mde L, Loguercio AD, Reis A, Muench A, de Araújo VC, et al.
(2005) Responses of human pulp capped with a bonding agent after
bleeding control with haemostatic agent. Oper Dent 30(2): 147-155.
68. Dammaschke T, Stratmann U, Fischer RJ, Sagheri D, Schäfer E, et al.
(2010) A histologic investigation of direct pulp capping in rodents withdentine adhesives and calcium hydroxide. Quintessence Int 41(4): 6271.
69. Gronthos S, Brahim J, Li W (2002) Stem cells properties of human dental
pulp stem cells. J Dent Res 81(8): 531-535.

70. Baume LJ, Holz J (1981) Long term clinical assessment of direct pulp
capping. Int Dent J 31(4): 251-260.
71. Hørsted P, Søndergaard B, Thylstrup A, El Attar K, Fejerskov O, et al.
(1985) A retrospective study of direct pulp capping with calcium
hydroxide compounds. Endod Dent Traumatol 1(1): 29-34.

72. Willershausen B, Willershausen L, Ross A, Velikonja S, Kasaj A, et al.
(2011) A retrospective study on direct pulp capping with calcium
hydroxide. Quintessence Int 42(2): 165-171.

73. Dammaschke T, Leidinger J, Schäfer E (2010) Long term evaluation of
direct pulp capping, treatment outcome over an average period of 6.1
years. Clin Oral Investig 14(5): 559-567.
74. Cox CF, Sübaby RK, Ostro E, Suzuki S, Suzuki SH (1996) Tunnel defects
in dentinal bridges, their formation following direct pulp capping. Oper
Dent 21(1): 4-11.

75. Bogen J, Kim JS, Bakland LK (2008) Direct pulp capping with mineral
trioxide aggregate, an observational study. J Am Dent Ass 139(3): 305315.
76. Farsi N, Almoudi N, Balto K, Al Mushayt A (2006) Clinical assessment ofmineral trioxide aggregate as direct pulp capping in young permanent
teeth. J Clin Pediatr Dent 31(2): 72-76.
77. Aeinehchi M, Eslami B, Ghanbariha M, Saffar AS (2003) Mineral trioxideaggregate and calcium hydroxide as pulp capping agents in human teeth,a preliminary report. Int Endod J 36(3): 225-231.

78. Min KS, Park HJ, Lee SK (2008) Effect of mineral trioxide aggregate on
dentine bridge formation and expression of dentine sialoprotein andheme oxygenase-1 in human dentinal pulp. J Endod 34(6): 666-670.

79. Nair PN, Duncan HF, Pitt Ford TR, Luder HU (2008) Histological,
ultrastructure and quantitative investigations of healthy human pulp
to experimental capping with mineral trioxide aggregate, a randomized
clinical trial. Int Endod J 41(2): 128-150.

80. Mente J, Gelentneky B, Ohle M (2010) Mineral trioxide aggregate
or calcium hydroxide direct pulp capping, an analysis of the clinicaltreatment outcome. J Endod 36(5): 806-813.
81. Olsburgh S, krejci I (2003) Pulp response to traumatic crown fractures.
Endod Topic 5(1): 25-40.
82. Cvek M (1978) A clinical report on partial pulpotomy and cappingwith calcium hydroxide in permanent incisors with complicated crown
fracture. J Endod 4(8): 232-237.

83. Chueh LH, Chiang CP (2010) Histology of irreversible pulpitis premolars
treated with mineral trioxide aggregate pulpotomy. Oper Dent 35(3):370-374.
84. Cvek M, Andreasen JO, Andreasen FM, Andreasen L (2007) Endodontic
management and use of calcium hydroxide in traumatized permanent
teeth. Textbook and color Atlas of traumatic injuries to teeth. (4th edn),
Ames, Lowa. Blackwell Munksgaard, USA, pp. 598-654.
85. Paranjpe A, Zhang H, Johnson JD (2010) Effect of mineral trioxideaggregate on human dental pulp cells after capping procedure. J Endod36(6): 1042-1047.

How to cite this article: Kareem A M K, Rasha M A. Managements of Immature Apex: a Review. Mod Res Dent. 1(1). MRD.000503. 2017.
DOI: 10.31031/MRD.2017.01.000503

23Modern Research in Dentistry
86. Mejare I, Cvek M (1993) Partial pulpotomy in young permanent teeth
with deep carious lesions. Endod Dent Traumatol 9(6): 238-242.
87. Svizero Nda R, Bresciani E, Francischone CE, Franco EB, Pereira JC, et al.
(2003) Partial pulpotomy and tooth reconstruction of a crown fractured
permanent incisor, a case report. Quintessence Int 34(10): 740-747.
88. Qudeimat MA, Barrieshi-Nusair KM, Owais AI (2007) Calcium hydroxidevs mineral trioxide aggregates for partial pulpotomy of permanentmolars of deep caries. Eur Arch Pediatr Dent 8(2): 99-104.

89. Trope M, Blanco L, Chivian N, Sigurdsson A, Cohen S, et al. (2006) The
role endodontics after dental traumatic injuries. Pathway of the pulp,(9th edn), Louis, Mosby, USA.

90. Koh ET, Fort TR, Kariyawansam SP, Chen NN, Torabinejad M, et al. (2001)
prophylactic treatment of dens evaginatus using mineral trioxideaggregate. J Endod 27(8): 540-542.
91. Chacko V, Kurikosa S (2006) Human pulpal reponse to mineral trioxideaggregate, a histological study. J Clin Pediatr Dent 30(3): 203-209.

92. El-Meligy OA, Avery DR (2006) Comparison of mineral trioxide aggregate
and calcium hydroxide as pulpotomy agents in young permanent teeth(apexogenesis). Pediatr Dent 28(5): 399-404.
93. Eghbal MJ, Asgary S, Baglue RA, Parirokh M, Ghoddusi J, et al. (2009)
MTA pulpotomy of human permanent molars with irreversible pulpitis.
Aust Endod 35(1): 4-8.

94. Witherspoon DE, Small JC, Harris GZ (2006) Mineral trioxide
pulpotomies, a case series outcome assessment. J Am Dent Ass 137(5):610-618.

Mod Res Dent

107. Cvek M, Sundstorm B (1974) Treatment of non-vital permanent
incisors with calcium hydroxide. V. Histological appearance ofroentgenographically demonstrable apical closure of immature roots:
Odontotol Revy 25(4): 379-391.

108. Barrieshi-Nusair KM, Qudeimat MA (2006) A prospective clinicalstudy of mineral trioxide aggregate for partial pulpotomy in cariously
exposed permanent teeth. J Endod 32(8): 731-735.
109. Chosack A, Sela J, Cleaton-Jones P (1997) A histological andquantitative histomorphometric study of apexification of non-vitalpermanent incisors of vervet monkey after repeated root filling withcalcium hydroxide paste. Endod Dent Traumatol 13(5): 211-217.

110. Yassen GH, Chin J, Mohammedsharif AG, Alsoufy SS, Othman SS, et al.
(2012) The effect of frequency of calcium hydroxide dressing changing
and varios pre- and inter-operative factors on endodontic treatmentof traumatized immature permanent incisors. Dent Traumatol 28(4):296-301.
111. Abbot P (1998) Apexification with calcium hydroxide-when should
the dressing be changed? The case for regular dressing changes. Aust
Endod J 24(1): 27-32.

112. Dominguez Reyes A, Munoz Munoz L, Aznar Martin T (2005) Study ofcalcium hydroxide apexification in 26 young permanent incisors. Dent
Traumatol 21(3): 141-145.
113. Fernandez-Yanez, Sanchez A, Leco-Berrocal MI, Martınez-Gonzalez JM(2008) Metaanalysis of filler materials in periapical surgery. Med Oral
Pathol Oral Cir Bucal 13(3): E180-E185.

95. Sangwan P, Sangwan A, Duhan J, Rohilla A (2013) Tertiary dentinogenesis
with calcium hydroxide, a review of proposed mechanisms. Int Endod J
46(1): 3-19.

114. Chala S, Abouqal R, Rida S (2011) 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 112(4): e36-e42.

97. Kontham UR, Tiku AM, Damle SG, Kalaskar RR (2005) Apexogenesis of asymptomatic mandibular first permanent molar with calcium hydroxide
pulpotomy. Quintessence Int 36(8): 653-657.

116. Huang GTJ (2009) Apexification, the beginning of its end. Int Endod J
42(10): 855-866.

96. Olsson H, Petersson K, Rohlin M (2006) Formation of hard tissue barrier
after pulp capping in humans, systematic review. Int Endod J 39(6): 429442.

98. Hørsted-Bindslev P, Løvschall H (2002) Treatment outcome of vital pulp
therapy. Endod Topic 2: 24-34.

99. Seo MS, Hwang KG, Lee J, Kim H, Baek SH, et al. (2013) The effect ofmineral trioxide aggregate on odontogenic differentiation in dental pulp
stem cells. J Endod 39(2): 242-248.

100. Sarkar NK, Caicedo R, Ritwik P, Moiseyeva R, Kawashima I, et al. (2005)
Physiochemical basis of the biologic properties of mineral trioxideaggregate. J Endod 31(2): 97-100.

101. Bozeman TB, Lemon RR, Eleazer PD (2006) Elemental analysis of
crystal precipitate from gray and white MTA. J Endod 32(5): 425-428.
102. Mosoud P, Torabinejad M (2010) Mineral trioxide aggregate, acomprehensive literature review. Part III: Clinical applications,drawbacks and mechanism of action. J Endod 36(3): 400-413.

103. Belobrov I, Parashos P (2011) Treatment of tooth discoloration after
the use of white mineral trioxide aggregate. J Endod 37(7): 1017-1020.
104. De-Deus G, de Souze MC, Sergio Fidel RA, Fidel SR, de Compos RC,
et al. (2009) Negligible expression of arsenic in some commerciallyavailable brands of Portland cement and mineral trioxide aggregate. J
Endod 35(6): 887-890.

105. Sheehy EC, Roberts GJ (1997) Use of calcium hydroxide for apicalbarrier formation and healing in non-vital immature permanent teeth,a review. Br Dent J 183(7): 241-246.
106. Chawla HS (1986) Apical closure in non-vital permanent tooth using
one calcium hydroxide dressing. J Dent Child 53(1): 44-47.

115. Bakland LK, Andreasen JO (2012) Will mineral trioxide aggregate
replace calcium hydroxide in treating pulpal and periodontal healing
complications subsequent to dental trauma, a review. Dent Trauamtol
28(1): 25-32.

117. Cvek M (1972) Treatment of non-vital permanent incisors withcalcium hydroxide. I Follow up of periapical repair and apical closureof immature roots. Odontotol Revy 23(1): 27-44.
118. Feiglin B (1985) Differences in apex formation during apexification
with calcium hydroxide paste. Endod Dent Traumatol 1(5): 195-199.
119. Sonoyama W, Seo BM, Yamaza T (2007) Human Hertwig’s epithelial
root sheath cells play crucial roles in cementum formation. J Dent Res
86(7): 594-599.

120. Fong CD, Davis MJ (2002) Partial pulpotomy of immature permanent
teeth, its present and future. Pediatr Dent 24(1): 29-32.

121. Nosrat IV, Nosrat CA (1998) Reparative hard tissue Formation
following calcium hydroxide application after partial pulpotomy incariously exposed pulps of permanent teeth. Int Endod J 31(3): 221226.
122. Bakland LK (2000) Management of traumatically injured pulps inimmature teeth using MTA. J Calif Dent Assoc 28(11): 855-858.
123. Karabucak B, Li D, Lim J, Iqbal M (2005) Vital pulp therapy withmineral trioxide aggregate. Dent Traumatol 21(4): 240-243.

124. Bogen G, Kutter S (2009) Mineral trioxide aggregate obturation, areview and case series. J Endod 35(6): 777-790.

125. Garcia-Godoy F, Murray PE (2012) Recommendations for using
regenerative endodontic procedures in permanent immaturetraumatized teeth. Dent Traumatol 28(1): 33-41.

How to cite this article: Kareem A M K, Rasha M A. Managements of Immature Apex: a Review. Mod Res Dent. 1(1). MRD.000503. 2017.
DOI: 10.31031/MRD.2017.01.000503

24Modern Research in Dentistry126. Belobrov L, Weis MV, Parashos P (2008) Conservative treatment ofcervical horizontal root fracture and a complicated crown fracture.
Aust Dent J 53(3): 260-264.

127. Kinirons MJ, Srivasan V, Welburg RR, Finucane D (2001) A study of twocenters of variations in the time of apical barrier detection and barrier
position in nonvital immature permanent incisors. Int J Pediatr Dent
11: 447-451.
128. Finucane D, Kinirons MJ (1999) Nonvital immature permanent
incisors: Factors that may influence treatment outcome. Endod Dent
Traumatol 15(6): 274-277.

129. Sarris S, Tahmassebi JF, Duggal MS, Cross IA (2008) A clinicalevaluation of mineral trioxide aggregate for root end closure of nonvital immature permanent incisors in children, a pilot study. Dent
Traumatol 24(1): 79-85.
130. Isidor F, Odman P, Brondum K (1996) Intermittent loading of teeth
restored using prefabricated carbon fiber posts. Int J Prosthodont9(2): 131-136.
131. Valois CR, Costa ED (2004) Influence of thickness of mineral trioxideaggregate on scaling ability of root end fillings in vitro. Oral Surg Oral
Med Oral Pathol Oral Radiol Endod 97(1): 108-124.
132. Warner JJ, Al-Salehi SK (2011) Mangement of open apex in a centeralincisor using mineral trioxide aggregate. Dent Update 38(1): 50-54.

133. Simon S, Rilliard F, Berdal A, Machtou P (2007) The use of mineral
trioxide aggregate in one visit apexification treatment, a prospective
study. Int Endod J 40(3): 186-197.

134. Bidar M, Disfani R, Gharagozloo S, Khoynezhad S, Rouhani A (2010)
Medication With calcium hydroxide improved marginal adaptation ofmineral trioxide aggregate apical barrier. J Endod 36(10): 1679-1682.
135. Hachmeister DR, Schindler WG, Walker WA (2002) The sealing ability
and retention characteristics of mineral trioxide aggregate in amodelof apexification. J Endod 28(5): 386-390.
136. Baldassari-Curz LA, Walton RE, Johnson WT (1998) Scanning electron
microscopy and histologic analysis of an apexification cap. : a casereport. Oral Med Oral Pathol Oral Radio Endod 86(4): 465-468.
137. Mente J, Leo M, Panagidis D, Ohle M, Schneider S, et al. (2013)
Treatment outcome of mineral trioxide aggregate in open apex teeth.
J Endod 39(1): 20-26.
138. Pradhan DP, Chawla
HS, Gauba K, Goyal A (2006) Comparativeevaluation of endodontic management of teeth with unformed apices
with mineral trioxide aggregate and calcium hydroxide. J Dent Child73(2): 79-85.
139. El-Meligy OA, Avery DR (2006) Comparison of apexification withmineral trioxide aggregate and calcium hydroxide. Pediatr Dent 28(3):248-253.
140. Grzesilk WJ, Narayanan AS (2002) Cementum and periodontal woundhealing and regeneration. Critical Rev Oral Bio Med 13(6): 474-484.
141. Solheim E (1998) Growth factors in bone. Int Orthop 22(6): 410-416.

142. Khatavkar RA, Hegde VS (2010) Use of matrix for apexification
procedure with mineral trioxide aggregate. J Conserv Dent 13(1): 5457.
143. Sood R, Kumar Hans M, Shetty S (2012) Apical barrier techniquewith mineral trioxide aggregate using internal matrix. A case report.
Compend Contin Educ Dent 33(6): e88-e90.

144. Cehreli ZC, Sara S, Uysal S, Turgut MD (2011) MTA apical plugs in thetreatment of traumatized immature teeth with large periapical lesions.
Dent Traumatol 27(1): 59-62.

145. Tezal B, Uysal S, Turgut MD, Cehreli ZC (2010) Inadvertent MTA
extrusion in immature traumatized permanent incisor. J Clin Pediatr
Dent 35(2): 145-148.

Mod Res Dent

146. Yates JA (1988) Barrier formation time in non-vital teeth with open
apex. Int Endod J 21(5): 313-319.
147. Kleier DJ, Barr ES (1991) A study of endodontically apexified teeth.
Endod Dent Traumatol 7(3): 112-117.

148. Felippe MCS, Felippe WT, Marques MM, Antoniazzi JH (2013) The
effect of the renewal of calcium hydroxide paste on the apexificationand periapical healing of teeth with incomplete root formation. Int
Endod J 38(7): 436-442.
149. Twati WA, Wood DJ, Liskiewicz TW, Willmott NS, Duggal MS, et al.
(2009) An evaluation of the effect of non-setting calcium hydroxide on
human dentine, a pilot study. Eur Arch Pediatr Dent 10(2): 104-109.
150. Sahebi S, Moazami F, Abbott P (2010) The effects of short-term calcium
hydroxide application on the strength of dentine. Dent Traumatol
26(1): 43-46.

151. Hatibovic-Koffman S, Raimundo L, Zheng L, Chong L, Friedman M, etal. (2008) Fracture resistance and histological findings of immature
teeth with mineral trioxide aggregate. Dent Traumatol 24(3): 272-276.
152. Tuna EB, Dinçol ME, Gençay K, Aktören O (2011) Fracture resistanceof immature teeth filled with Bio Aggregate, mineral trioxide aggregate
and calcium hydroxide. Dent Traumatol 27(3): 174-178.
153. Yassen GH, Platt JA (2013) The effect of non-setting calcium hydroxideon root fracture and mechanical properties of radicular dentine: asystematic review. Int Endod J 46(2): 112-118.

154. Sarkar NK, Caicedo R, Ritwik P, Moiseyeva R, Kawashima I, et al. (2005)
Physicochemical basis of the biologic properties of mineral trioxideaggregate. J Endod 31(2): 97-100.
155. Al Ansary MA, Day PF, Duggal MS, Brunton PA (2009) Interventions
for treating traumatized necrotic immature permanent anterior teeth:
inducing a calcific barrier & root strengthening. Dent traumatol 25(4):367-379.
156. Lertchirakarn V, Poonkaew A, Messer H (2011) Fracture resistance ofroots filled with gutta-percha or RealSeal®. Int Endod J 44(11): 10051010.

157. Weiger R, Heuchert T, Hahn R, Löst C (1995) Adhesion of glass ionomer
cement to human radicular dentine. Endod Dent Traumatol 11(5):214-219.
158. Sengun A, Cobankara FK, Orucoglu H (2008) Effect of a new restoration
technique on fracture resistance of endodontically treated teeth. Dent
traumatol 24(2): 214-219.
159. Lawley GR, Schindler WG, Walker WA, Kolodrubetz D (2004) Evaluationof ultrasonically placed MTA and fracture resistance with intracanalcomposite resin in a model of apexification. J Endod 30(3): 167-172.

160. Camp HJ, Fuks AB, Cohen S, Burns RC (2006) Pediatric endodontics:
Endodontic treatment for the primary and young permanent dentition.
Pathway of the pulp, (9th edn), St Louis, Mosby, USA, p. 874.
161. Katebzadeh N, Dalton BC, Trope M (1998) Strengthening immature
teeth during and after apexification. J Endod 24(4): 256-259.

162. Goldberg F, Kaplan A, Roitman M, Manfre S, Picca M, et al. (2002)
Reinforcing effect of a resin modified glass ionomer in the restorationof immature roots in vitro. Dent Traumatol 18(2): 70-72.
163. Duret B, Duret F, Reynaud M (1996) Long-life physical property
preservation and postendodontic rehabilitation with the composipost.
Compend Contin Educ Dent Suppl (20): S50–S56.

164. Norsat A, Nekfoofar MH, Bolhari B, Dummer PM (2012) Unintended
extrusion of mineral trioxide aggregate, a report of three cases. Int
Endod J 45(12): 1165-1176.
165. Bose R, Nummikoski P, Hargreaves K (2009) A retrospective evaluationof radiographic outcomes in immature teeth with necrotic root canalsystems treated with regenerative endodontic procedures. J Endod35(10): 1343-1349.

How to cite this article: Kareem A M K, Rasha M A. Managements of Immature Apex: a Review. Mod Res Dent. 1(1). MRD.000503. 2017.
DOI: 10.31031/MRD.2017.01.000503

25

Modern Research in Dentistry166. Chueh LH, Ho YC, Kuo TC, Lai WH, Chen YH, et al. (2009) Regenerative
endodontic treatment for necrotic immature permanent teeth. J Endod35(2): 160-164.
167. Thibodeau B (2009) Case report, pulp revascularization of necrotic,
infected, immature, permanent tooth. Pediatr Dent 31(2): 145-148.
168. Ding RY, Cheung GS, Chen J, Yin XZ, Wang QQ, et al. (2009) Pulp
revascularization of immature teeth with apical periodontitis, a clinicalstudy. J Endod 35(5): 745-749.

169. Jung IY, Lee SJ, Hargreaves KM (2008) Biologically based treatment ofimmature permanent teeth with pulpal necrosis, a case series. J Endod34(7): 876-887.

170. Banchs F, Trope M (2004) Revascularization of immature permanent
teeth with apical periodontitis, new treatment protocol. J Endod 30(4):196-200.
171. Sato I, Ando-Kurihara N, Kota K, Iwaku M, Hoshino E, et al. (1996)
Sterilization of infected root-canal dentine by topical application ofa mixture of ciprofloxacin, metronidazole and minocycline in situ. Int
Endod J 29(2): 118-124.
172. Galler KM, D’Souza RN, Federlin M, Cavender AC, Hartgerink JD, etal. (2011) Dentin conditioning codetermines cell fate in regenerative
endodontics. J Endod 37(11): 1536-1541.

173. Trevino EG, Patwardhan AN, Henry MA, Perry G, Dybdal-Hargreaves N,
et al. (2011) Diogenes Effect of irrigants on the survival of human stem
cells of the apical papilla in a platelet-rich plasma scaffold in humanroot tips. J Endod 37(8): 1109-1115.
174. Kim JH, Kim Y, Shin SJ (2010) Tooth discoloration of immature
permanent incisor associated with triple antibiotic therapy: a casereport. J Endod 36(6): 1086-1091.

175. Al-Omiri MK, Mahmoud AA, Rayyan MR, Abu-Hammad O (2010)
Fracture resistance of teeth restored with post-retained restorations:an overview. J Endod 36(9): 1439-1449.
176. Trope M (2010) Treatment of the immature tooth with a non-vital pulp
and apical periodontitis. Dent Clin North Am 54(2): 313-324.

177. Reynolds K, Johnson JD, Cohenca N (2009) Pulp revascularizationof necrotic bilateral bicuspids using a modified novel technique toeliminate potential coronal discolouration: a case report. Int Endod J
42(1): 84-92.
178. Cotti E, Mereu M, Lusso D (2008) Regenerative treatment of animmature, traumatized tooth with apical periodontitis: report of acase. J Endod 34(5): 611-616.
179. Morfis AS, Siskos G (1991) Apexification with the use of calcium
hydroxide, a clinical study. J Clin Pediatr Dent 16(1): 13-19.

180. Cehreli ZC, Isbitiren B, Sara S, Erbas G (2011) Regenerative endodontic
treatment (revascularization) of immature necrotic molars medicatedwith calcium hydroxide: a case series. J Endod 37(9): 1327-1330.
181. Huang GTJ (2008) A paradigm shift in endodontic management ofimmature teeth, conservation of stem cells for regeneration. J Dent
36(6): 379-386.
182. Chueh LH, Huang GT (2006) Immature teeth with periradicularperiodontitis or abscess undergoing apexogenesis, a paradigm shift. J
Endod 32(12): 1205-1213.
183. Shin SY, Albert JS, Mortman RE (2009) One step pulp revascularization
treatment of an immature permanent tooth with chronic apicalabscess, a case report. Int Endod 42(12): 1118-1126.

184. Sonoyama W, Liu Y, Yamaza T (2008) Characterization of the apical
papilla and its residing stem cells from human immature permanent
teeth: a pilot study. J Endod 34(2): 166-171.

Mod Res Dent

185. Wang X, Thibodeau B, Trope M (2010) Histological characterizationof regenerated tissues in canal space after the revitalization/
revascularization procedure of immature dog teeth with apicalperiodontitis. J Endod 36(1): 56-63.

186. Cvek M (1992) Prognosis of luxated non-vital maxillary incisors treatedwith calcium hydroxide and filled with gutta-percha, a retrospective
study. Endod Dent Traumatol 8(2): 45-55.
187. Carlson ME, Conboy IM (2007) Loss of stem cell regenerative capacity
within aged niches. Aging Cell 6(3): 371-382.

188. Huang GT (2009) Pulp and dentin tissue engineering and regeneration,
current progress. Regenerative Medicine 4(5): 697-707.
189. Nakashima M, Iohara K, Zheng L (2006) Gene therapy for dentin
regeneration with bone morphogenetic proteins. Current Gene
Therapy 6(5): 551-560.

190. Yamauci N, Yamauchi S, Nagaoka H (2011) Tissue engineering
strategies for immature teeth with apical periodontitis. J Endod 37(3):390-397.
191. Torabinejad M, Turman M (2011) Revitalization of tooth with necrotic
pulp and open apex by using platelet-rich plasma, a case report. J
Endod 37(2): 265-268.

192. Nosrat A, Seifi A, Asgary S (2011) Regenerative endodontic treatment(revascularization) for necrotic immature permanent molars, a review
and report of two cases with a new biomaterial. J Endod 37(4): 562567.

193. Kim DS, Park HJ, Yeom JH, Seo JS, Ryu GJ, et al. (2012) Long-term followups of revascularized immature necrotic teeth, three case reports. Int
J Oral Sci 4(2): 109-113.
194. Yassen GH, Chu TM, Eckert G, Platt JA (2013) Effect of medicaments
used in endodontic regeneration technique on the chemical structureof human immature radicular dentin: an in vitro stud. J Endod 39(2):269-273.
195. Iwaya SI, Ikawa M, Kubota M (2001) Revascularization of an immature
permanent tooth with apical periodontitis and sinus tract. Dent
Traumatol 17(4): 185-187.

196. Thibodeau B, Trope M (2007) Pulp revascularization of a necrotic
infected immature permanent tooth, case report and review of theliterature. Pediatr Dent 29(1): 47-50.

197. Vojinovic O (1981) The endodontic method of treatment of apicalperiodontitis in immature and young permanent teeth. J Int Ass Dent
Child 12: 65-72.
198. da Silva L, Nelson-Filho P, da Silva R (2010) Revascularization andperiapical repair after endodontic treatment using apical negative
pressure irrigation versus conventional irrigation plus triantibiotic
intracanal dressing in dogs’ teeth with apical periodontitis. Oral Surg
Oral Med Oral Pathol Oral Radiol Endod 109(5): 779-787.

199. Chen MY, Chen KL, Chen CA, Tayebaty F, Rosenberg PA, et al. (2012)
Responses of immature permanent teeth with infected necrotic pulp
tissue and apical periodontitis/abscess to revascularization procedure.
Int Endod J 45(3): 294-305.
200. Lovelace TW, Henry MA, Hargreaves KM, Diogenes A (2011) Evaluationof the delivery of mesenchymal stem cells into the root canal spaceof necrotic immature teeth after clinical regenerative endodontic
procedure. J Endod 37(2): 133-138.
201. Mackie IC, Bentley EM, Worthington HV (1988) The closure of open
apices in non-vital immature incisor teeth. Br Dent J 165(5): 167-173.

202. Pace R, Giuliani V, Pini Prato L, Baccetti T, Pagavino G, et al. (2007)
Apical plug technique using mineral trioxide aggregate. Int Endod J
40(6): 478-484.

How to cite this article: Kareem A M K, Rasha M A. Managements of Immature Apex: a Review. Mod Res Dent. 1(1). MRD.000503. 2017.
DOI: 10.31031/MRD.2017.01.000503

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Mod Res Dent

Modern Research in Dentistry203. Holden DT, Schwartz SA, Kirkpatrick TC, Schindler WG (2008) Clinicaloutcome of artificial root end barriers with mineral trioxide aggregate
in teeth with immature apices. J Endod 34(7): 812-817.
204. Witherspoon DE, Small JC, Regan JD, Nunn M (2008) Retrospective
analysis of open apex teeth obdurate with mineral trioxide aggregate. J
Endod 34(10): 1171-1176.

205. Moore A, Howley MF, O’Connell AC (2011) Treatment of open apex
teeth using two types of white mineral trioxide aggregate after initialdressing with calcium hydroxide in children. Dent Traumatol 27(3):166-173.

206. Tahan E, Celik D, Er K, Taşdemir T (2010) Effect of unintentionally
extrusion of mineral trioxide aggregate in treatment of tooth withperiapical lesion: a case report. J Endod 36(4): 760-763.
207. Asmussen E, Peutzfeldt A, Heitmann T (1999) Stiffness, elastic limit
and strength of newer types of endodontic posts. J Dent 27(4): 275278.

208. Petrino JA, Boda KK, Shambarger S (2010) Challenges in regenerative
endodontics, a case series. J Endod 36(3): 536-541.

209. Hargreaves K, Geisler T, Henry M, Wang Y (2008) Regeneration
potential of the young permanent tooth. what does the future hold? J
Endod 34(7 Suppl): S51-S56.

210. Hibodeau B, Teixeira F, Yamauchi M, Caplan D, Trope M, et al. (2007)
Pulp revascularization of immature dog teeth with apical periodontitis.
J Endod 33(6): 680-689.
211. Lenzi R, Trope M (2012) Revitalization procedures in two traumatized
incisors with different biological outcomes. J Endod 38(3): 411-414.

212. Nosrat A, Homayounfar N, Oloomi K (2012) Drawbacks and unfavorable
outcomes of regenerative endodontic treatments of necrotic immature
teeth, a literature review and report of a case. J Endod 38(10): 14281434.

How to cite this article: Kareem A M K, Rasha M A. Managements of Immature Apex: a Review. Mod Res Dent. 1(1). MRD.000503. 2017.
DOI: 10.31031/MRD.2017.01.000503

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