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Treatment of Mature Permanent Teeth with Necrotic Pulpsand Apical Periodontitis Using Regenerative EndodonticProcedures: A Case SeriesTarek Mohamed Saoud, BDS, MSC, PhD,* Gabriela Martin, DDS, PhD,†

Yea-Huey M. Chen, DDS, MS, ‡ Kuang-Liang Chen, DDS, ‡ Chao-An Chen, DDS, ‡

Kamolthip Songtrakul, DDS, MS, § Matthew Malek, DDS, § Asgeir Sigurdsson, DDS, MS, §

and Louis M. Lin, BDS, DMD, PhD §

Abstract

Introduction: Regenerative endodontic procedures(REPs) are usually used to treat human immature perma-nent teeth with necrotic pulps and/or apical periodonti-tis. Successful REPs result in the elimination of clinical

signs/symptoms, the resolution of apical periodontitis,and, in some cases, thickening of the canal walls and/or continued root development with or without apicalclosure. REPs can restore the vitality of tissue in thecanals of immature permanent teeth previouslydestroyed by infection or trauma. Vital tissue is inheritedwith immune defense mechanisms to protect itself fromforeign invaders. Recently, REPs have also been used tosuccessfully treat human mature permanent teeth withnecrotic pulps and apical periodontitis. The purpose of this case series was to present the potential of usingREPs for mature permanent teeth with necrotic pulpsand apical periodontitis. Methods: This case series con-sisted of 6 patients, 4 females and 2 males. The patients’

ages ranged from 8–21 years old. Seven permanentteeth, 4 anterior and 3 molar teeth, with necrotic pulpsand apical periodontitis were treated using REP. Radio-graphically, the root development of all teeth wasalmost completed except the apices of 2 molars, whichshowed slightly open. Complete chemomechanicaldebridement of the canals of the teeth was performed,and the canals were dressed with Metapaste (Meta Bio-med Co, Ltd, Chungbuk, Korea) during treatment visits.Periapical bleeding into the canals was induced at thelast treatment visit by placing a hand #20 or #25 K-filewith the tip slightly bent through the apical foraminainto the periapical tissues. A 3-mm thickness of

mineral trioxide aggregate was placed into the coronalcanals over semicoagulated blood. The access cavitieswere restored with either composite resin or amalgam.

Results: Follow-ups of the 7 teeth ranged from 8 to 26 months. The periapical lesionsof 2 teeth were considered healed, and 5 teeth revealed healing. Clinical signs/symp-toms were absent in all teeth at follow-up visits at different time points. None of thetreated teeth responded to cold and electric pulp tests. Conclusions: This case series

shows the potential of using REPs for mature teeth with necrotic pulp and apical peri-odontitis. (J Endod 2015;-:1–9)

Key WordsApical periodontitis, immune defense mechanisms, mature teeth, necrotic pulps, regen-erative endodontic therapy, vital tissue

Regenerative endodontics is defined as biologically based procedures designed tophysiologically replace a damaged tooth structure, including dentin and root struc-tures, and the pulp-dentin complex (1). Regenerative endodontic procedures (REPs)are currently used to treat immature permanent teeth with infected or noninfectednecrotic pulps (2). REPs have been shown to be able to eliminate clinical signs/symp-toms and resolve apical periodontitis. In addition, thickening of the canal walls and/orcontinued root development have been shown in some cases (3–5). According to the American Association of Endodontists Clinical Considerations for a RegenerativeProcedure, the primary goal of REPs is elimination of clinical signs/symptoms andresolution of apical periodontitis (6). Increased thickening of the canal walls and/orcontinued root development are secondary goals in those considerations (6). There-fore, it can be stated that the primary goal of REPs is similar to that of nonsurgical root canal therapy.

Traditionally, mature permanent teeth with infected or noninfected necrotic pulpsare treated with nonsurgical root canal therapy, which includes chemomechanical debridement, intracanal mediation, and root filling. The outcome of nonsurgical rootcanal therapy is considered predictable (7). Recently, REPs have been used to suc-cessfully treat mature teeth with necrotic pulps and apical periodontitis (8–10). Thetreatment also resulted in the elimination of clinical signs/symptoms and resolutionof apical periodontitis. The difference between nonsurgical root canal therapy and

an REP is that the disinfected canals are filled with biocompatible, nonvital foreignmaterials in the former therapy and vital tissue in the latter therapy.

From the*Department of Endodontics, Faculty of Dentistry, University of Benghazi, Benghazi, Libya; †Department of Endodontics, Faculty of Dentistry, NationalUniversity of Cordoba, Cordoba, Argentina; ‡Department of Endodontics, Chi Mei Medical Center, Yong Kang and Liouying, Tainan, Taiwan; 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 1000. E-mail address:[email protected]/$ - see front matter

Copyright ª 2015 American Association of Endodontists.http://dx.doi.org/10.1016/j.joen.2015.09.015

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JOE — Volume-, Number-,- 2015 Teeth with Necrotic Pulps and Apical Periodontitis 1

mailto:[email protected]://dx.doi.org/10.1016/j.joen.2015.09.015http://dx.doi.org/10.1016/j.joen.2015.09.015mailto:[email protected]

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Thetissues generatedin thecanals of humanimmature permanent teethwith infected necroticpulps and apical periodontitis after REPsarecementumlike, bonelike, periodontal ligament–like tissues; blood ves-sels; and nerve fibers (11–14). Although these tissues are not true pulptissue, they are the host’s own vital tissue, which is inherited withimmune defense mechanisms to protect itself from foreign invaders.Therefore, REPs are able to restore the vitality of tissue in the canalsof immature permanent teeth that was previously destroyed by infection or trauma. However, it is not known whether tissues can begenerated in the canals of human mature permanent teeth after REPsbecause there are no histologic studies available.

Based on previous case reports (8–10) and the primary goal of REPs, it was believed that REPs might have the potential to be used totreat human mature permanent teeth with infected or noninfectednecrotic pulp. The purpose of this case series was to present thepotential of using REPs for human mature permanent teeth withinfected or noninfected necrotic pulps and apical periodontitis interms of elimination of clinical signs/symptoms and resolution of apical periodontitis. The present case series is part of our multi-institutional clinical trials of REPs for human mature permanent teeth with infected or noninfected necrotic pulps. Written informed consents were obtained from the patients.

Case SeriesSix patients were treated in the endodontic clinic at the faculty of

dentistry, University of Benghazi. The patients’ chief complaint and thedental and medical histories were obtained. Preoperative radiographsof allteethwere taken. Pulp tests usingcold, heat, and an electric pulptester were performed. Intraoral and extraoral examinations wereconducted. Swelling, the presence of draining sinus tracts, and toothdiscoloration were recorded. A diagnosis of pulpal-periapical disease was based on the chief complaint, clinical signs/symptoms, pulp tests,and radiographic findings.

The demographics of the patients are summarized in Table 1. Thepresent case series consisted of 6 patients, 4 females and 2 males. Thepatients’ ages ranged from 8–21 years. Seven mature teeth, 4 anterior

and 3 molar teeth, were treated using REPs. Three teeth had caries, which caused pulp necrosis and apical periodontitis. Five teeth had a history of trauma and subsequently developed pulp infection and apical periodontitis. Four teeth were associated with intraoral swelling. Twotraumatized teeth showed discoloration. Radiographically, the rootsof all teeth had a periapical radiolucent lesion of endodontic origin(Table 2). The root development of all teeth was almost complete,except the apices of the distal roots of 2 mandibular first molars

(#19), which showed exhibited slightly open (Figs. 1 A– D and 2 A– D).

Summary of Treatment ProceduresTo avoid repetition of some treatment procedures among 7 cases,

the treatment procedures are summarized as follows.

First Treatment Visit. Local anesthetic with 2% lidocaine contain-ing 1:100,000 epinephrine was given as local infiltration for anteriorteeth and an inferior alveolar block for molar teeth. The endodontically involved tooth was isolated with a rubberdam. All caries were removed.The access cavity was made through the lingual surface of the crown of anterior teeth and the occlusal surface of the crown of molar teeth. Thecanal/canals were located. The pulp chamber was irrigated with 2.5%sodium hypochlorite solution (Household Cleaning Products Company of Egypt, Cairo, Egypt). A working length 0.5 mm short of the radio-graphic apex was determined with the electronic apex locator and peri-apical radiographs. The canals were initially instrumented to the working length with hand K-files to #20 and then prepared with Pro-Taper Universal rotary files (Dentsply International, Ballaigues,Switzerland) to F1 (tip size #20) with copious amounts of sodium hy-pochlorite irrigation during instrumentation. The canals were dried with paper points and dressed with Metapaste (calcium hydroxide;Meta Biomed Co, Ltd, Chungbuk, Korea). The access cavity was closed with a sterile cotton pellet and intermediate restorative material (IRM)(Dentsply International) for 2 weeks.

Second Treatment Visit. Under local anesthesia with 2% lido-caine containing 1:100,000 epinephrine, the tooth was isolated with

a rubber dam and reopened. The cotton pellet and IRM were removedfrom the access cavity. Metapaste was flushed out of the canal with so-dium hypochlorite irrigation. The canal was again prepared with Pro-Taper Universal Rotary files to F5 (tip size #40) for teeth #8 and #9and F3 (tip size #30) for tooth #25. The mesiobuccal and mesiolingual canalswereprepared toF2 (tipsize#25) and the distal canals to F4 (tipsize #35) of teeth #19 and #30 with copious amounts of sodium hypo-chlorite irrigation. After complete chemomechanical debridement, a #15 K-file was used to penetrate into the periapical tissues throughall canals to ensure the patency of the apical foramina. The canals were dried and dressed with Metapaste. The access cavity was closed with a cotton pellet and IRM for 2 weeks.

TABLE 1. Demographics of Patients

Patient no. Sex Age (y) Tooth no.

1 M 14 252 F 18 8, 93 F 21 84 M 11 305 F 9 196 F 8 19

F, female; M, male.

TABLE 2. Clinical Signs/Symptoms, Diagnosis, and Treatment Outcomes of 7 Teeth Treated Using RET

Patientno.

Toothno. Dental history Clinical examination Clinical tests

Radiologicexamination

Clinicaldiagnosis

Periapicalstatus

Last control(month)

1 25 Trauma Tooth discoloration e(), pc(), pp() PAP PN and AAP Healed 132 8 Trauma pain Crown fracture e(), pc(+), pp(+) PAP PN and SAP Healing 12

9 Trauma pain Crown fracture e(), pc(+), pp(+) PAP PN and SAP Healing 123 8 Trauma intraoral

swelling,sinus tract

Tooth discoloration e(), pc(+), pp(+) PAP PN and CAA Healed 26

4 30 Caries Intraoral swelling e(), pc(+), pp(+) PAP PN and AAA Healing 125 19 Caries Intraoral swelling e(), pc(+), pp(+) PAP PN and AAA Healing 126 19 Caries Intraoral swelling e(), pc(+), pp(+) PAP PN and AAA Healing 8

AAA, acute apical abscess; AAP, asymptomatic apical periodontitis; CAA, chronic apical abscess; e, electric pulp test; PAP, periapical pathology; pc, percussion; PN, pulp necrosis; pp, palpation; SAP, symptomatic

apical periodontitis.

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Third Treatment Visit. Local anesthetic with 3% Carbocaine(Septodont, Paris, France) without vasoconstrictor was administered.The tooth was reopened, and the cotton pellet and IRM were removedfrom the access cavity under rubber dam isolation. Metapaste wasflushed out of the canals with sodium hypochlorite irrigation. The ca-nals were dried andrinsed with sterile salinesolution and dried. Finally,the canals were irrigated with 17% EDTA and dried with paper points. A

hand #25 K-file with the tip slightly bent was introduced 3 mm into theperiapical tissues through the distal canals of teeth #19and #30 andthecanals of other teeth (#8, #9, and #25), whereas a #20 K-file was usedfor the mesiobuccal and mesiolingual canals of teeth #19 and #30 toprovoke bleeding into the canals up to the canal orifices under theobservation of a magnifying surgical loupe. Bleeding could not beachieved to the canal orifices of the mesiobuccal and mesiolingual canals of teeth #19 and #30. An attempt was made to provide bleedingfrom the distal canals to the mesial canals. After approximately 15 mi-nutes, when the blood became semicoagulated, a 3-mm thickness of mineral trioxide aggregate (MTA; Dentsply Tulsa Dental, Tulsa, OK)mixed with saline solution to a putty consistence was placed into thecoronal canals using an amalgam carrier. Collagen matrix was not used because the canal space of mature teeth was not as large as that

of immature teeth. A moist cotton pellet was placed over MTA, andthe access cavity was closed with IRM for 3 days. Postoperative radio-graphs were taken.

Fourth Treatment Visit. Without local anesthesia, the IRM andcotton pellet were removed under rubber dam isolation. Setting of MTA was confirmed with an endodontic explorer. The access cavities were restored with either composite resin or amalgam.

Follow-up ExaminationFollow-ups of 7 cases ranged from 8 to 26 months (Table 1).

Radiographic assessment of the change in periapical lesions of 7 teethafter treatment was evaluated based on the criteria of healed, healing,and disease used by Orstavik et al (15, 16). Healed is defined as noclinical signs/symptoms and normal periapical radiographicpresentation. Healing is reduced periapical radiolucency and noclinical signs/symptoms. Disease is new development or persistenceof periapical radiolucency or the presence of clinical signs/symptoms(16). Two teeth were considered healed, and 5 teeth revealed healingat their last control (Table 1). All teeth were asymptomatic at theirfollow-up visits with no response to cold or electric pulp tester tests.

Figure 1. ( A) A preoperative radiograph of tooth #19. Small periapical radiolucent lesions at the apices of the mesial and distal roots. The roots are fully devel-oped. The apex of the distal root is slightly open. ( B ) A postoperative radiograph after REPs. (C ) Seven-month follow-up, evidence of healing of periapical radio-lucent lesions of both roots. ( D) Twelve-month follow-up, periapical radiolucent lesions of both roots show healing. The tooth was asymptomatic.

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We lost contact with patient #6 after the 8-month follow-up. Radio-graphs of the treatment outcomes of 7 cases using REPs are shown inFigures 1–6.

DiscussionMature permanent teeth with necrotic pulps and/or apical peri-

odontitis are traditionally treated with nonsurgical root canal therapy because the treatmentoutcome is considered predictable (7). Recently,REPs have been used to successfully treat mature permanent teeth withinfected necrotic pulps and apical periodontitis. The treatment resultedin elimination of clinical signs/symptoms and resolution of apical peri-odontitis (8–10). In the present case series, we have presented 7 casesof mature permanent teeth with necrotic pulps and apical periodontitissuccessfully treated using REPs.

The root development of mandibular first molars normally com-pletes at 9 or 10 years of age. Although the apices of the distal rootsof 2 mandibular first molars (#19) were slightly open, which could

be because of apical periodontitis, we considered that these 2 molarscould be treated as mature teeth because the development of the canal walls and the root length of the distal roots were nearly completed.

The size of the apical foramen appears to be a major concern in

REPs. It wassuggested that an apicalforamenof at least 1.1mm in diam-eter was necessary for successful revascularization of the pulp tissue inreimplanted human permanent incisors (17). Therefore, humanmature permanent teeth with completely formed root apices havingnecrotic pulps were considered not suitable for REPs. However, a study using an animalmodel showedthatan apical foramen 0.32 mm in diam-eter did not prevent revascularization and ingrowth of new tissue intocanals after transplantation (18).

In studying regeneration of dental pulp–like tissue by chemotaxis-induced cell homing, the apical foramina of the humanmature permanent incisors and canines were not enlarged. Dental pulp–like tissue was formed in the entire root canal from the root apex to thepulpchamberupondelivery of growth factors into theche-momechanically debrided canals of the teeth implanted in mouse

Figure 2. ( A) A preoperative radiograph of tooth #19. A large periapical radiolucent lesion at the apex of the distal root and thickening of periodontal ligament space at the apex of the mesial root. Both mesial and distal roots are well developed. ( B ) A postoperative radiograph after REPs. (C ) Five-month follow-up, evidenceof healing of periapical radiolucent lesions at both roots. ( D) Eight-month follow-up, periapical radiolucent lesions of both roots show healing. The tooth wasasymptomatic. The patient lost contact after the 8-month follow-up.

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dorsum (19). Complete pulp regeneration in the canals of matureteeth with closed apices was also observed after pulpectomy by trans-plantation of autologous pulp CD105+ stem cells with stromal cell–

derived factor-1 implanted in dogs (20). Furthermore, it was shownhistologically that new tissues could be generated in the canals of mature teeth with necrotic pulps and apical periodontitis after anREP when the canals were instrumented to a #60 K-file in an animal model (21).

In human REP studies of mature permanent teeth with necroticpulps and apical periodontitis, Shah and Logani (8) enlarged the apical foramen to a #30 K-file, Paryani and Kim (9) to a #60 K-file, and Saoudet al (10) to a #35 K-file. Based on these animal and human studies, it can be concluded that the size of the apical foramen does not have to be1 mm in diameter for new tissue to grow into the canals after REP. How-ever, enlargement of the apical foramen to a large size may facilitate theingrowth of newtissue into the canal from theperiapical area after REPsof mature teeth.

Proper control of root canal infection is the key to success of end-odontic treatment in terms of elimination of clinical signs and/or symp-toms and resolution of apical periodontitis (22, 23). Contemporary

root canal infection control protocols, including mechanical instrumentation, sodium hypochlorite irrigation, and intracanal medication with calcium hydroxide are not able to eliminate all bacteria in the root canal system because of its anatomic complexity (24, 25). Calcium hydroxide, the popular intracanal medication inroot canal therapy, has its shortcomings in eliminating intracanal bacteria because dentin and hydroxylapatite have an inhibitory effect on the antimicrobial activity of calcium hydroxide (26). The triple anti-biotic paste (ciprofloxacin, metronidazole, and minocycline) may alsohave limitations in killing intracanal bacteria. It hasbeen shown that tri-ple antibiotic paste was capable of disinfecting the infected root dentinand eliminating bacteria in vitro (27, 28). However, these in vitroexperiments did not exactly simulate the clinical situation in whichthe teeth indicated for regenerative endodontic therapy usually have

Figure 3. ( A) A preoperative radiograph of tooth #25. A well-defined periapical radiolucent lesion at the apex. The root is completely formed. ( B ) A postoperativeradiograph after REPs. (C ) Ten-month follow-up, healing of periapical radiolucent lesion. ( D) Thirteen-month follow-up, the periapical radiolucent lesion ishealed. The tooth was asymptomatic.

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had a long-standing history of infection with well-established biofilm inthe canal and bacteria in the dentinal tubules. An in vivo study also

showed that triple antibiotic paste was able to eliminate most but not all bacteria in artificially infected root canals in dogs (29). Ciprofloxa-cin inhibits DNA gyrase synthesis, metronidazole inhibits DNA synthesis,and minocycline inhibits protein synthesis of microbes (30). These an-tibiotics are effective when microbes are in an active state of replicationand synthesis of cell walls, proteins, or DNA but not in a stationary state.Therefore, residual bacteria arelikely to remainin thecanals of infectedmature or immature permanent teeth after root canal disinfection usingsodium hypochlorite irrigation and intracanal medication with calciumhydroxide and/or triple antibiotic paste.

Another concern of REPs for mature or immature permanent teeth with infected necrotic pulp and/or apical periodontitis is the residual bacteria in the root canal system because they may grow in unfilled ca-

nals. Therefore, root filling is recommended and expected to prevent coronal leakage, retard residual bacteria in the canal from penetratinginto the periapical tissues, and, hopefully, entomb bacteria in the canal in nonsurgical root canal therapy. However, a systematic review of theoutcome of primary root canal treatment does not support that theseexpectations always occur because it is well recognized that theoutcome of root canal therapy in cases of teeth with necrotic pulpsand apical periodontitis is not always successful (7).

The fate of bacteria remaining in the canals and root dentinal tu-bules after REPs of mature or immature permanent teeth with infectednecrotic pulps is notknown. In nonsurgical root canal therapy, residual bacteria in the root dentinal tubules after properly chemomechanical debridement do not appear to be the primary cause of post-treatment apical periodontitis (31). In fact, inflammatory periapical lesions

were able to heal even without root fillings if root canal infection wasproperly controlled and coronal leakage was prevented in human

and animal studies (32, 33). There are no convincing studies tosupport that bacteria in the root dentinal tubules are capable of sustaining or inducing apical periodontitis of endodontically involvedteeth after proper root canal therapy.

The induction of periapical bleeding into the disinfected canal of immature or mature permanent teeth during REPs brings mesenchymal stem cells (34) and likely growth factors (platelet-derived growth fac-tor, platelet-derived endothelial growth factor, transforminggrowth fac-tor, and insulinlike growth factor) mainly derived from platelets as well as fibrin scaffold (35, 36) from the periapical tissues into the canal space. Also included are components of innate and adaptive immunesystem, such as antibacterial molecules (complement componentsand immunoglobulins), phagocytes (polymorphonuclear leukocytes

and macrophages), antimicrobial peptides, and cytokines. All thesebioactive proteins and immune cells are contained in the blood (37).Complement component C3b can opsonize bacteria, and immunoglob-ulinscan coat and localizebacteria to facilitate phagocytosisby activatedpolymophonuclear leukocytes and macrophages through C3b and Fcreceptors on these phagocytes. In addition, mesenchymal stem cellscan secrete antimicrobial peptide LL-37 (38); up-regulate genesinvolved in promoting phagocytosis and bacterial killing (39); andaugment the antibacterial activity of immune cells and secret largeamounts of interleukin (IL)-6, IL-6, IL-8, and tumor necrosis factorcytokines to recruit and activate polymorphonuclear leukocytes (40).It was also suggested that LL-37 might contribute to regeneration of the dentin-pulp complex in regenerative endodontics (41). The induc-tion of periapical bleeding into the canals during REPs may enhance

Figure 4. ( A) A preoperative radiograph of teeth #8 and #9. Well-defined periapical radiolucent lesions at the apices of teeth #8 and #9, respectively. The roots of teeth #8 and #9 are completely developed. ( B ) A postoperative radiograph of both teeth after REPs. (C ) Seven-month follow-up, there is evidence of healing of periapical radiolucent lesions of both teeth. ( D) Twelve-month follow-up, the periapical lesions of #8 and #9 show healing. Both teeth were asymptomatic.

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antimicrobial clearance in the canals. In addition, the possibility that residual bacteria in the canals may also be killed by immune defensemechanisms of generated vital tissue after REPs cannot be ruled out.This rationaleis supportedby the high success rate of immatureperma-nent teeth with infected pulps and apical periodontitis after REPs (2).However, there are case reports showing periapical wound healing,

thickening of the canal walls, and/or continued root development without inducing periapical bleeding into the canals after revasculariza-tion (42–44). The interaction between the numbers and virulence of microbes and the host resistance plays an important role inmicrobial infection (30).

It is not known whether tissue can be generated in the canals of human mature permanent teeth with necrotic pulps after REPsbecause there are no histologic studies available. In an animal model,cementumlike, bonelike, and periodontal ligament–like tissues wereobserved generated in the canals of mature teeth with necrotic pulpsand apical periodontitis after REPs (21). These tissues are similar tothose tissues generated in the canals of immature teeth with necroticpulps and apical periodontitis after REPsin humans and animals (11–

14, 45, 46). Although the tissues generated in the canals of matureteeth in an animal model after REPs are not pulp tissue, they arethe host’s vital tissue. In our previous case reports (10, 47), 2mature permanent teeth, one with necrotic pulp and apical periodontitis and another one with persistent apical periodontitisafter root canal therapy, showed thickening of the canal walls andapical closure after REPs. These observations indicate that cellscapable of producing mineralized tissue have migrated into thecanals and formed hard tissue on the canal walls and at the root apex. Therefore, similar to an animal study (21), it is likely that new vital tissue might also be able to generate in the canals of humanmature permanent teeth with necrotic pulps after REPs.

Vital tissue is endowed with an immune defense mechanism todetect and protect itself from foreign invaders, such as bacteria.

Recently, it was shown that the induction of periapical bleeding intothe disinfected root canals of human mature teeth with necrotic pulpsand apical periodontitis during REPs was able to bring apical mesen-chymal stem cells into the canal space (48). These multipotent mesen-chymal stem cells are capable of differentiating into different cell lineages depending on the differentiation signals that they receive and

produce tissue/tissues to replace the pulp tissue in the canals of matureteeth destroyed by infection or trauma (21).

The goal of treating disease is to assist the host’s natural woundhealing processes by enhancing innate and adaptive immune defensemechanisms to eliminate irritants and create a favorable microenviron-ment conducive for tissue regeneration and/or repair to occur. The in-duction of bleeding is the first phase of wound healing processes. REPsappear to be able to promote the host’s wound healing processes andrestore the vitality of tissue in the canals previously destroyed by infec-tion or trauma. In contrast, a traditional nonsurgical root canal therapy prevents the host’s natural wound healing processes and the restorationofvitalityofdamagedtissueinthecanaltotakeplace.Biologically,itmay be preferable to have disinfected root canals filled with the host’s own

vital tissues rather than with nonvital foreign materials. Pulpal biology and endodontic therapy are finally coming together (49).In general, periapical lesions of teeth in the healing group had a

short follow-up. It is possible that, given more time, the healing groupcould become the healed group (42).

Similar to revascularization of immature permanent teeth with in-fected necrotic pulps and apical periodontitis reported by Iwaya et al in2001 (50), REPs for mature permanent teeth with infected or nonin-fected necrotic pulps are still in the early stage of clinical trials. If more case reports and case series of REPs for mature permanent teeth with infected or non-infected necrotic pulps show favorable treatment outcomes, REPsmay become a feasible treatmentfor mature permanent teeth with infected or noninfected necrotic pulps. Hopefully, our multi-institutional clinical trials of REPs for mature teeth with infected or

Figure 5. ( A) A preoperative radiograph of tooth #8. A small periapical radiolucent lesion at the apex. The root is completely formed. ( B ) A postoperative radio-graph after REPs. (C ) Twelve-month follow-up, healing of periapical radiolucent lesion of tooth #8. ( D) Twenty-six month follow-up, periapical radiolucent lesionof tooth #8 is healed. Note that tooth #9 was treated with nonsurgical root canal therapy. Tooth #8 was asymptomatic.

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noninfected necrotic pulps will provide more information about treat-ment outcomes in the near future.

Conclusion

Based on the present case series, REPs, a biologically based ther-apy, have the potential to be used to treat mature permanent teeth withinfected necroticpulpand apical periodontitis in termsof elimination of clinical signs/symptoms and resolution of apical periodontitis. Howev-er, randomized, prospective clinical trials are needed to compare theoutcome of nonsurgical root canal therapy and REPs formature perma-nent teeth with infected necrotic pulps andapical periodontitis. In addi-tion to randomized, prospective clinical trials, long-term follow-ups of cases are required to show complete healing and no recurrence of api-cal pathosis.

Acknowledgments

The authors deny any conflicts of interest related to this study.

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Figure 6. ( A) A preoperative radiograph of tooth #30, small periapical radiolucent lesions at the apices of the mesial and distal roots. The roots are fully formed.( B ) A postoperative radiograph after REPs. (C ) Eight-month follow-up, evidence of healing of periapical radiolucent lesions at both roots. ( D) Twelve-monthfollow-up, periapical radiolucent lesions of both roots show healing. The tooth was asymptomatic.

Clinical Research


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Clinical Research

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