Case Report/Clinical Techniques

Management of Teeth with Persistent Apical

Periodontitis after Root Canal Treatment Using
Regenerative Endodontic Therapy
Tarek Mohamed A. Saoud, BDS, MSc, PhD,* George T.-J. Huang, DDS, MDS, DSc,†
Jennifer L. Gibbs, MAS, DDS, PhD,‡ Asgeir Sigurdsson, DDS, MS,‡
and Louis M. Lin, BDS, DMD, PhD‡

Abstract
Regenerative endodontic therapy (RET) is currently Key Words
used to treat immature teeth with necrotic pulp and/or Apical periodontitis, immune defense, regenerative endodontic therapy, retreatment,
apical periodontitis. However, recently RET has been vital tissue
used to treat mature teeth with necrotic pulp and/or
apical periodontitis and resulted in regression of clin-
ical signs and/or symptoms and resolution of apical
periodontitis. The purpose of this case report was to
R egenerative endodontics (RET) is defined as biologically based procedures designed
to physiologically replace a damaged tooth structure, including dentin and root struc-
tures, as well as the pulp-dentin complex (1). RET includes irrigation with copious
describe the potential of using RET to treat 2 mature amounts of 1.5% sodium hypochlorite, intracanal medication with calcium hydroxide
teeth with persistent apical periodontitis after root ca- and triple antibiotic paste (ciprofloxacin, metronidazole, and minocycline), and 17%
nal therapy using RET. Two male patients, one 26-year EDTA rinse of the canal without mechanical debridement before induction of intracanal
old and another 12-year old, presented for retreatment bleeding (2). RET is currently used to treat immature permanent teeth with infected or
of persistent apical periodontitis after root canal treat- noninfected necrotic pulps (2). The treatment can result in regression of clinical signs/
ment of 2 mature teeth (#9 and #19). The gutta-percha symptoms as well as resolution of apical periodontitis. In addition, thickening of the canal
fillings in the canals of teeth #9 and #19 were removed walls and/or continued root development may occur in some cases (3–5). According to
with Carvene gutta-percha solvent (Prevest DenPro, the American Association of Endodontists guidelines, the primary goals of RET are
Jammu, India) and ProTaper Universal rotary retreat- resolution of apical periodontitis and elimination of clinical signs/symptoms (6).
ment files (Dentsply Maillefer, Ballaigues, Switzerland). Increased thickening of the canal walls and/or continued root development as well as
The canals of both teeth were further chemomechani- regaining a positive response to pulp testing are desirable but not essential to determine
cally debrided with rotary retreatment files and copious the clinical success of RET (6). The primary goals of RET are similar to those of nonsur-
amounts of sodium hypochlorite irrigation and dressed gical root canal therapy. Therefore, RET might have the potential to be used to treat
with Metapaste (Meta Biomed, Chungbuk, Korea). mature teeth with infected or noninfected necrotic pulps and teeth with persistent apical
RET was performed on teeth #9 and #19. Periapical periodontitis after root canal therapy.
bleeding was provoked into the disinfected root canals. Histologically, normal-looking pulp tissue has not been reported to regenerate in
The blood clots were covered with mineral trioxide the canals of human immature permanent teeth with infected or noninfected necrotic
aggregate plugs, and the access cavities were restored pulps after RET (7). However, cementumlike, bonelike, and periodontal ligament–like
with intermediate restorative material. Teeth #9 tissue and neurovascular supply have been observed regenerated in the canals of human
and #19 showed regression of clinical signs and/or immature permanent teeth with infected or noninfected necrotic pulps (8–11). Although
symptoms and healing of apical periodontitis after these tissues are not pulp tissue, they are vital tissues, which are inherited with immune
13-month and 14-month follow-ups, respectively. defense mechanisms. Therefore, RET can restore the vitality and defense capability of the
Tooth #9 revealed narrowing of the canal space and tissue damaged in the canals of human immature permanent teeth with infected necrotic
apical closure by deposition of hard tissue. RET has pulps.
the potential to be used to retreat teeth with persistent Recently, mature permanent teeth with necrotic pulps and apical periodontitis
apical periodontitis after root canal therapy. (J Endod have been successfully treated using RET (12–14). The treatment eliminates clinical
2015;41:1743–1748) signs/symptoms and resolves apical periodontitis. The tissues regenerated in the
canals of human mature permanent teeth with infected necrotic pulps are not known
because there are no histologic studies available. However, cementumlike, bonelike,

From the *Department of Endodontics, Faculty of Dentistry, University of Benghazi, Benghazi, Libya; †Department of Bioscience Research, College of Dentistry, Uni-
versity of Tennessee Health Science Center, Memphis, Tennessee; and ‡Department of Endodontics, College of Dentistry, New York University, New York, New York.
Address requests for reprints to Dr Louis M. Lin, Department of Endodontics, NYU College of Dentistry, 345 East 24th Street, New York, NY 10010. E-mail address:
lml7@nyu.edu
0099-2399/$ - see front matter
Copyright ª 2015 American Association of Endodontists.
http://dx.doi.org/10.1016/j.joen.2015.07.004

JOE — Volume 41, Number 10, October 2015 Teeth with Persistent Apical Periodontitis 1743
Case Report/Clinical Techniques
and periodontal ligament–like tissues and vasculature were shown Treatment Procedures
regenerated in the canals of mature teeth with necrotic pulps and First Treatment Visit. At the time of the treatment visit, localized
apical periodontitis in an animal model (15). These tissues are similar intraoral swelling was still present. Tooth #9 was asymptomatic. Local
to those tissues regenerated in the canals of human immature perma- anesthesia with 2% lidocaine containing 1:100,000 epinephrine was
nent teeth with infected necrotic pulps and apical periodontitis (8–11). administered. Tooth #9 was isolated with a rubber dam. The canal
Teeth with persistent apical periodontitis after root canal therapy was accessed, and the root canal filling was identified. The poorly fitted
are primarily caused by persistent root canal infection or root canal rein- gutta-percha cones were removed with a Hedstrom file #20 (Dentsply
fection (16, 17). Therefore, more complete root canal infection control Maillefer, Ballaigues, Switzerland). The working length (WL) 0.5 mm
of unsuccessfully treated teeth is important in retreatment. The short of the radiographic apex was determined with an electronic
unsuccessfully treated teeth are usually managed with nonsurgical or apex locator and periapical radiography. The canal was prepared using
surgical retreatment to eliminate root canal infection and apical ProTaper Universal rotary retreatment files D1 (tip size #30/.09), D2
periodontitis (18, 19). Surgical retreatment is recommended when (tip size #25/.08), and D3 (tip size #20/.07) (Dentsply Maillefer) to
nonsurgical retreatment is not feasible. The outcome of nonsurgical or the WL with copious amounts of 2.5% sodium hypochlorite irrigation
surgical retreatments is predictable (18, 19). (Household Cleaning Products Company of Egypt, Cairo, Egypt).
Most recently, Nevins and Cymerman (20) reported the successful Because tooth #9 had a large canal space and an open apex, it was
retreatment of 2 teeth with persistent apical periodontitis after nonsur- sequentially debrided to hand #60 K-files to the WL. The canal was irri-
gical root canal therapy using a revitalization procedure or RET. Based gated, dried, and dressed with Metapaste (calcium hydroxide with
on the results of mature teeth with infected necrotic pulps and apical barium sulfate; Meta Biomed, Korea). The access cavity was closed
periodontitis successfully treated using RET (12–14), it was believed with a sterile cotton pellet and intermediate restorative material
that teeth with persistent apical periodontitis after root canal therapy (IRM) (Dentsply DeTrey, Konstanz, Germany).
might also be able to be managed using RET because the objectives
and goals of primary and secondary root canal treatment are the
Second Treatment Visit. Two weeks after the first treatment visit,
the localized swelling had subsided, and the tooth remained asymptom-
same. The purpose of this case report was to describe the potential
atic. Local anesthesia with 2% mepivacaine without a vasoconstrictor
of using RET to treat 2 teeth with persistent apical periodontitis after
was administered. The tooth was isolated with a rubber dam. The
root canal therapy.
IRM and cotton pellet were removed from the access cavity. Metapaste
in the canal was removed with copious amounts of sodium hypochlorite
Case Reports irrigation, and the canal was gently debrided with a hand #60 K-file, irri-
Case 1 gated, and dried. The canal was rinsed with saline solution and dried
and then irrigated with 17% EDTA and dried with paper points. A
A 26-year-old man presented to the dental clinic of the faculty of
#25 K-file was used to penetrate the periapical tissue and provoke peri-
dentistry with pain and labial swelling associated with his maxillary ante-
apical bleeding into the canal under the observation of magnifying sur-
rior teeth. The patient’s medical history was noncontributory. The
gical loupes. After the bleeding became semicoagulated, a mineral
dental history revealed that the patient had a traumatic injury to his
trioxide aggregate (MTA) plug (Dentsply Tulsa Dental, Tulsa, OK) of
maxillary anterior teeth more than 10 years ago. Subsequently to the
approximately 3-mm thickness was placed over the semicoagulated
trauma, a general dentist performed conventional root canal therapy
blood clot. A moist cotton pellet was placed over the MTA plug, and
on teeth #8 and #9. Tooth #9 was restored with porcelain fused to metal
the access cavity was closed with IRM (Fig. 1B).
full crown coverage. The crown of tooth #8 was partially restored with
composite resin. At some point, the crown of tooth #9 fell off, likely Third Treatment Visit. Three days after the second treatment visit,
because of poor fit. the IRM and cotton pellet were removed from the access cavity. It was
Extraoral examination revealed slight labial swelling of the maxilla. determined that the MTA plug had completely set after examination with
There were no palpable lymph nodes in the head and neck. Intraoral an endodontic explorer. The access cavity was restored with light-
examination showed that hard bony swelling was localized labially in curing composite resin, and the patient was advised to have the tooth
the periapical region of tooth #9. The full crown coverage on tooth permanently restored with a crown by his dentist.
#9 was missing, and the tooth was tender to percussion and palpation.
Tooth #8 was asymptomatic and not tender to percussion and palpation. Follow-up Examinations
Conventional periapical radiography showed that tooth #9 had a large At the 7-month follow-up, the periapical lesion had slightly
canal space, which was poorly obturated with root filling, and a periap- decreased in size (Fig. 1C). At the 13-month follow-up, the periapical
ical radiolucent lesion (Fig. 1A). Tooth #8 also had a root canal filling lesion showed further radiographic evidence of healing. The canal
but no periapical lesion (Fig. 1A). Both teeth had completely formed space appeared slightly decreased in size because of thickening of
roots. The periodontal pocket probings of both teeth #9 and #8 were the canal walls relative to the postoperative radiograph, and the apex
within normal limits (3–4 mm). appeared to have closed (Fig. 1D). The tooth was restored with a tem-
Based on the dental history and clinical radiographic findings, tooth porary crown. The tooth did not respond to pulp tests with cold, heat,
#9 was diagnosed as previously treated acute apical abscess. Treatment and electric pulp test at the 7-month and the 13-month follow-ups.
options including nonsurgical root canal retreatment, RET, and extrac-
tion were presented to the patient. The outcome of secondary root canal
treatment was discussed with the patient. The patient was informed that Case 2
the outcome of RET for teeth with persistent apical periodontitis after root A 12-year-old boy accompanied by his mother presented to the
canal therapy was not known. The patient opted for RET. endodontic clinic with a referral from the pediatric dentistry depart-
The intraoral swelling was hard and localized and not very painful ment of the faculty of dentistry for the evaluation of tooth #19. The
to palpation. Therefore, an incision and draining were not performed. patient’s medical history was not contributory. The dental history
The patient was advised to take ibuprofen as needed for pain and sched- indicated that because of a deep carious lesion, the general dentist
uled for endodontic retreatment in a week. performed root canal therapy on tooth #19 17 months ago. Extraoral

1744 Saoud et al. JOE — Volume 41, Number 10, October 2015
 Case Report/Clinical Techniques

Figure 1. (A) A preoperative periapical radiograph. Teeth #8 and #9 have conventional root canal therapy. Tooth #9 has poor root canal filling and a large
periapical radiolucent lesion and no coronal restoration. (B) A postoperative periapical radiograph of tooth #9 after RET. (C) At the 7-month follow-up, the peri-
apical lesion had decreased in size. (D) At the 13-month follow-up, the periapical lesion showed further healing. There is narrowing of the canal space and closure
of the apex.

examination showed that the submandibular lymph node was slightly Treatment Procedures
enlarged. Intraoral examination revealed that there was localized First Treatment Visit. The local swelling was still present, and
swelling on the lingual aspect of the left mandibular molar area, which tooth #19 was asymptomatic. Local anesthesia with 2% lidocaine con-
was tender to palpation. The tooth was also sensitive to percussion. A taining 1:100,000 epinephrine was administered as a block of the left
healing draining sinus tract was present on the buccal aspect of tooth inferior alveolar nerve. The tooth was isolated with a rubber dam. Caries
#19 near the periapical area, which was not traced. There was no cor- was completely removed. The access cavity was irrigated with 2.5% so-
onal restoration, and recurrent caries was observed in the access cav- dium hypochlorite solution and dried. Carvene gutta-percha solvent
ity of tooth #19. The root canal fillings in the mesiobuccal and (Prevest DenPro, Jammu, India) was dripped onto the cavity floor via
mesiolingual canals and the distal canals were exposed to the oral an irrigation syringe. The gutta-percha cones in the mesiobuccal and
environment. Conventional radiography showed poorly obturated mesiolingual canals and the distal canals were carefully removed with
root canals and a large periapical radiolucent lesion involving both #15 H-files (Dentsply Maillefer) and ProTaper Universal rotary retreat-
the mesial and distal roots (Fig. 2A). Both the mesial and distal roots ment file D1. The WL 0.5 mm short of the radiographic apex was deter-
were completely formed. The periodontal pocket probings were mined with an electronic apex locator and periapical radiography. The
within normal limits (3–4 mm). mesiobuccal and mesiolingual canals were subsequently prepared with
Based on the dental history and clinical and radiographic find- rotary retreatment file D3 and the distal canal with D2. The canals were
ings, the diagnosis for tooth #19 was previously treated chronic apical copiously irrigated with 2.5% sodium hypochlorite solution, dried with
abscess. Treatment options including nonsurgical root canal retreat- paper points, and dressed with Metapaste. The access cavity was closed
ment, RET, and extraction were presented to the patient and the pa- with a sterile cotton pellet and IRM.
tient’s mother. They were also informed of the prognosis for each
treatment option. The patient’s mother and the patient decided to Second Treatment Visit. A week after the first treatment visit, the
try RET of tooth #19. The patient was scheduled for endodontic re- local swelling had subsided. An inferior alveolar block with 2% lido-
treatment in a week. caine containing 1:100,000 epinephrine was given. Tooth #19 was

JOE — Volume 41, Number 10, October 2015 Teeth with Persistent Apical Periodontitis 1745
Case Report/Clinical Techniques

Figure 2. (A) A postoperative periapical radiograph of tooth #19. The tooth has poor root canal therapy and a large periapical radiolucent lesion involving the
mesial and the distal roots and no coronal restoration. (B) A postoperative periapical radiograph of tooth #19 after RET. (C) At the 8-month follow-up, healing of
the periapical lesion is observed. (D) At the 14-month follow-up, there is complete periapical healing of the distal root and slight thickening of the periodontal
ligament space of the mesial root.

isolated with a rubber dam. The cotton pellet and IRM were removed points. A hand #25 K-file was used to penetrate into the periapical tissue
from the access cavity. The mesiobuccal and mesiolingual canals from each canal to provoke periapical bleeding into all canals observed
were mechanically instrumented with rotary retreatment files D3 and with magnifying surgical loupes. After the bleeding became semicoagu-
the distal canal with a hand #35 K-file along with abundant sodium hy- lated, MTA plugs of approximately 3-mm thickness were placed over the
pochlorite irrigation. The canals were dried with paper points and semicoagulated blood clot in all canals. A moist cotton pellet was placed
dressed with Metapaste. The access cavity was temporized with a sterile over the MTA plugs, and the access cavity was closed with IRM (Fig. 2B).
cotton pellet and IRM. Fifth Treatment Visit. A week after the third treatment visit, the
Third Treatment Visit. Because of scheduling difficulty, the pa- IRM and cotton pellet were removed from the access cavity. It was deter-
tient returned 1 ½ months later for the continuation of treatment. Tooth mined that the MTA plug had completely set after examination with an
#19 remained asymptomatic. Radiographically, the periapical lesion endodontic explorer. The access cavity was temporarily restored with
appeared to be decreased in size. Local anesthesia with 2% lidocaine IRM, and the patient’s mother and the patient were advised to have
containing 1:100,000 epinephrine was administered. The tooth was iso- the tooth permanently restored by his dentist.
lated with a rubber dam, and IRM and the cotton pellet were removed
from the access cavity. Metapaste was removed from the canals with
Follow-up Examinations
copious amounts of sodium hypochlorite irrigation. The mesiobuccal
At the 8-month follow-up, radiographic evidence of healing of the
and mesiolingual canals were hand instrumented to #30 K-files and
periapical lesion was observed (Fig. 2C). At the 14-month follow-up,
the distal canal to a #40-K file to the WL with copious amounts of sodium
there was complete periapical healing of the distal root and slight thick-
hypochlorite irrigation. The canals were irrigated with sodium hypo-
ening of the periodontal ligament space of the mesial root (Fig. 2D). The
chlorite, dried with paper points, and dressed with Metapaste. The ac-
cess cavity was sealed with a cotton pellet and IRM. tooth was not permanently restored. The tooth did not respond to pulp
tests with cold, heat, and electric pulp test at the 8-month and 14-month
Fourth Treatment Visit. Tooth #19 was asymptomatic. Local anes- follow-ups.
thetic of 3% mepivacaine without a vasoconstrictor was given. The tooth
was isolated with a rubber dam. IRM and the cotton pellet were removed
from the access cavity. Metapaste in the canal was removed with copious Discussion
amounts of sodium hypochlorite irrigation. The mesiobuccal and me- Teeth with persistent apical periodontitis after root canal therapy
siolingual canals were gently debrided with a #30 K-file and the distal are primarily caused by persistent root canal infection or root canal
canal with a #40 K-file with sodium hypochlorite irrigation. The canals reinfection (16, 17). Systematic reviews of primary and secondary
were dried with paper points, rinsed with saline solution and dried with root canal treatments indicate that the outcome of secondary
paper points, and then irrigated with 17% EDTA and dried with paper treatment is poorer than the primary treatment (18, 21). Therefore,

1746 Saoud et al. JOE — Volume 41, Number 10, October 2015
 Case Report/Clinical Techniques
secondary root canal treatment is more difficult than primary root canal root canal therapy successfully reduces the bacterial load to the
treatment. The microbial flora in teeth undergoing secondary root canal subthreshold level in the canal, at which point the innate and
treatment is single species of the predominantly gram-positive organism adaptive immune defense mechanisms of the periapical tissues are
Enterococcus faecalis (22), which is resistant to intracanal medication capable of eliminating the bacteria (33, 34). The same principle may
(ie, calcium hydroxide) (23) but might not be resistant to immune de- apply to RET of immature and mature teeth with necrotic pulps and
fense mechanisms of regenerated vital tissue after RET. apical periodontitis. The regenerated vital tissue in the canals after
Teeth with persistent apical periodontitis after root canal therapy RET is also endowed with immune defense mechanisms. Therefore,
are usually retreated with nonsurgical (18, 19) or surgical procedures wound healing could occur in the infected canals after RET
(19). Surgical treatment is recommended when nonsurgical treatment depending on the numbers of bacteria and their virulence and the
is not feasible. The long-term outcome of both treatments is predictable host’s immune defense (35, 36).
(18, 19). In the present case report, we have described the potential of After the induction of bleeding into the canal, the host’s humoral
using RET to retreat teeth with persistent apical periodontitis after root (complement components and immunoglobulins) and cellular
canal therapy. In our previous publication, we have discussed the (phagocytes, lymphocytes) components of the immune system con-
possible advantages of vital tissue regenerated in the canals of mature tained in the circulation are brought into the canal. For bacteria to sur-
teeth with necrotic pulps and apical periodontitis using RET (14). Vital vive in vital tissue, they have to be able to evade the host’s immune
tissue is endowed with innate and adaptive immune defense mecha- defense mechanisms, such as avoidance of opsonization by comple-
nisms and neurovascular supply to detect and protect tissues from ment component C3b, binding by antibody (immunoglobulin), and
foreign invaders such as bacteria. recognition by Toll-like receptor of immune cells as well as resistance
The size of the apical foramen was an issue in revascularization or to phagocytosis by phagocytes and killing by phagolysosomes.
regenerative endodontic therapy. However, studies appear to indicate It is not known whether new tissue could be regenerated in the
that the size of the apical foramen is not critical to revascularization canals of teeth with persistent apical periodontitis after root canal ther-
or regenerative endodontic therapy (15, 24–26). This has also been apy using RET. In the present case report, the canal space of tooth #9
discussed in our previous publication (14). decreased in size after RET, likely because of deposition of hard tissue
The major concern in RET of mature or immature teeth with in- on the canal walls. This finding was also observed in our previous case
fected necrotic pulp and/or apical periodontitis is the residual bacteria report of mature teeth with necrotic pulps and apical periodontitis after
in the canals and the root dentinal tubules because residual bacteria RET (14). The hard tissue can only be formed by mineralized tissue-
may grow in the unfilled canals. Contemporary root canal disinfection forming cells, which must have migrated into the canal after RET. There-
protocols including the use of antibiotics are not able to eliminate all fore, thickening of the canal walls and apical closure can also occur in
bacteria in the infected root canal system because of its anatomic mature teeth with necrotic pulps and apical periodontitis after RET. It
complexity (27). Therefore, root filling is necessary and expected to has been shown histologically that the tissues regenerated in the canals
prevent coronal leakage, retard residual bacteria in the canal from of mature teeth with necrotic pulps and apical periodontics after RET
penetrating into the periapical tissues, and hopefully entomb bacteria are cementumlike, bonelike, and periodontal ligament–like tissues in
in the canal in nonsurgical root canal treatment. Root filling may be an animal model (15). Although these tissues are not pulp tissue,
able to achieve some but not all 3 expectations. Otherwise, teeth with they are vital tissue. It is likely that such vital tissue might also be regen-
infected necrotic pulps and apical periodontitis after root canal therapy erated in the canals of teeth with persistent apical periodontitis after root
should be able to accomplish complete periapical healing. A systematic canal therapy, which was retreated using RET in humans in the 2 cases
review of the outcome of primary root canal treatment does not support presented here. However, currently, there are no histologic studies
this notion (21). In RET, the possibility that the residual bacteria in the available in humans.
canals may be eliminated by immune defense mechanisms of regener- In conclusion, if mature teeth with necrotic pulp and apical peri-
ated vital tissue cannot be ruled out. This rationale is supported by the odontitis can be treated using RET (12–14), teeth with persistent apical
high success rate of immature permanent teeth with infected necrotic periodontitis after root canal therapy may also be managed with RET
pulps after RET (2). after careful root canal infection control (20). The treatment objectives
The fate of bacteria remaining in the root dentinal tubules after and goals of nonsurgical root canal therapy and RET are the same—
proper chemomechanical debridement is not known. In nonsurgical elimination of clinical signs/symptoms and healing of apical periodon-
root canal therapy, residual bacteria in the root dentinal tubules do not titis. It may be preferable to fill the disinfected root canals with the host’s
appear to be the primary cause of post-treatment apical periodontitis own vital tissue rather than with nonvital foreign material. However, ran-
(28). In fact, an inflammatory periapical lesion is able to heal even without domized, prospective clinical trials are needed to compare the treat-
root filling if root canal infection is properly controlled and the coronal ment outcome of conventional root canal treatment and RET for teeth
seal is able to prevent root canal reinfection (29, 30). There are no with persistent apical periodontitis after root canal therapy.
convincing studies to show that bacteria in the root dentinal tubules are
capable of sustaining or inducing apical periodontitis of endodontically
involved teeth after proper root canal therapy. However, it must be Acknowledgments
emphasized that effective control of root canal infection is always The authors deny any conflicts of interest related to this study.
pivotal to endodontic therapy including nonsurgical root canal
treatment and RET (31, 32).
It is possible for wound healing to occur in the canals after RET if References
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