biologically based treatment of immature permanent teeth ... · teeth with pulpal necrosis: a case...

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Biologically Based Treatment of Immature Permanent Teeth with Pulpal Necrosis: A Case Series Il-Young Jung, DDS, MS,* Seung-Jong Lee, DDS, MS,* and Kenneth M. Hargreaves, DDS, PhD Abstract This case series reports the outcomes of 8 patients (ages 9 –14 years) who presented with 9 immature permanent teeth with pulpal necrosis and apical peri- odontitis. During treatment, 5 of the teeth were found to have at least some residual vital tissue remaining in the root canal systems. After NaOCl irrigation and medication with ciprofloxacin, metronidazole, and mi- nocycline, these teeth were sealed with mineral trioxide aggregate and restored. The other group of 4 teeth had no evidence of any residual vital pulp tissue. This second group of teeth was treated with NaOCl irriga- tion and medicated with ciprofloxacin, metronidazole, and minocycline followed by a revascularization proce- dure adopted from the trauma literature (bleeding evoked to form an intracanal blood clot). In both groups of patients, there was evidence of satisfactory postop- erative clinical outcomes (1–5 years); the patients were asymptomatic, no sinus tracts were evident, apical periodontitis was resolved, and there was radiographic evidence of continuing thickness of dentinal walls, api- cal closure, or increased root length. (J Endod 2008;34: 876 – 887) Key Words Endodontics, immature permanent tooth, open apex, regenerative, revascularization, stem cell A lthough contemporary nonsurgical endodontic procedures confer high degrees of clinical success (1, 2), the root canal system is obturated with synthetic materials, preventing any of the advantages that might ensue by regeneration of a functional pulp-dentin complex (3). This is a particular problem when treating the necrotic but immature permanent tooth, where conventional treatment often leads to resolution of apical periodontitis, but the tooth remains susceptible to fracture (4) as a result of interruption of apical and dentinal wall development. Thus, one alternative approach would be to develop and validate biologically based endodontic procedures designed to restore a functional pulp-dentin complex. For more than 50 years, clinicians have evaluated biologically based methods to restore a functional pulp-dentin complex in teeth with necrotic root canal systems caused primarily by trauma or caries. Although case series from the 1960s–1970s in general were not successful in producing this outcome (5, 6), it should be appreciated that they were performed without contemporary instruments or materials and without insight generated from the trauma or tissue engineering fields (7). More recent case reports, published during the last 15 years, have demonstrated that it is possible in humans to restore a functional pulp-dentin complex in the necrotic immature perma- nent tooth (8 –13). Human histologic studies have not yet been reported, so it is not known whether these treatments truly recapitulate the normal pulp-dentin complex. However, these case studies provide some measure of achieving satisfactory functional outcomes, because postoperative recalls indicate that the patient is asymptomatic, no sinus tracts are present, apical periodontitis is resolved, and there is radiographic evidence of continuing thickness of dentinal walls, apical closure, or development of root length. Although case series do not provide definitive evidence to support a given treat- ment modality, they do have the advantage of being conducted in actual patients and thus provide greater insight than preclinical studies. Moreover, the results from case series can be used to identify potentially important parameters that can guide the design of future prospective clinical trials. For example, in nearly all published case series on pulpal regeneration, an effort was made to evoke an intracanal blood clot to trigger tissue ingrowth. In this case series, we report conditions in which it was not necessary to evoke intracanal bleeding to have continued root development. Pulp Regeneration without Formation of a Blood Clot Case 1 A 10-year-old girl was referred to the Department of Conservative Dentistry of the Dental Hospital of Yonsei University by an oral and maxillofacial surgeon for evaluation on the right second mandibular premolar (tooth #29). The girl had a history of swelling of the right mandibular buccal vestibule, for which she received an incision for drainage procedure at the Department of Oral and Maxillofacial Surgery 2 months earlier. On clinical examination, the patient was slightly symptomatic to percussion, and a sinus tract was present that traced to the apex of tooth #29. The first and second premolars were free of caries, but a fracture of an occlusal tubercle of tooth #29 was noted on visual inspection. Periodontal probings were within normal limits for all teeth in the lower right region. Diagnostic testing was inconclusive on cold and electric pulp testing, but the patient reported sensitivity to percussion or palpation. Periradicular radio- graphic examination revealed that tooth #29 had an incompletely developed apex and a periradicular radiolucency (Fig. 1A). The diagnosis of pulp necrosis and chronic apical abscess with a sinus tract was made for tooth #29. From the *Department of Conservative Dentistry, Yonsei University School of Dentistry, Seoul, Korea; and Department of Endodontics, University of Texas Health Science Center at San Antonio, San Antonio, Texas. Address requests for reprints to Dr Seung-Jong Lee, De- partment of Conservative Dentistry, Yonsei University School of Dentistry, 134 Shinchon-Dong, Sudaemun-Ku, Seoul, Korea 120-752. E-mail address: [email protected]. 0099-2399/$0 - see front matter Copyright © 2008 American Association of Endodontists. doi:10.1016/j.joen.2008.03.023 Case Report/Clinical Techniques 876 Jung et al. JOE — Volume 34, Number 7, July 2008

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Page 1: Biologically Based Treatment of Immature Permanent Teeth ... · Teeth with Pulpal Necrosis: A Case Series Il-Young †Jung, DDS, MS,* Seung-Jong Lee, DDS, MS,* and Kenneth M. Hargreaves,

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Case Report/Clinical Techniques

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iologically Based Treatment of Immature Permanenteeth with Pulpal Necrosis: A Case Series

l-Young Jung, DDS, MS,* Seung-Jong Lee, DDS, MS,* and Kenneth M. Hargreaves, DDS, PhD†

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bstracthis case series reports the outcomes of 8 patientsages 9 –14 years) who presented with 9 immatureermanent teeth with pulpal necrosis and apical peri-dontitis. During treatment, 5 of the teeth were foundo have at least some residual vital tissue remaining inhe root canal systems. After NaOCl irrigation andedication with ciprofloxacin, metronidazole, and mi-ocycline, these teeth were sealed with mineral trioxideggregate and restored. The other group of 4 teeth hado evidence of any residual vital pulp tissue. Thisecond group of teeth was treated with NaOCl irriga-ion and medicated with ciprofloxacin, metronidazole,nd minocycline followed by a revascularization proce-ure adopted from the trauma literature (bleedingvoked to form an intracanal blood clot). In both groupsf patients, there was evidence of satisfactory postop-rative clinical outcomes (1–5 years); the patients weresymptomatic, no sinus tracts were evident, apicaleriodontitis was resolved, and there was radiographicvidence of continuing thickness of dentinal walls, api-al closure, or increased root length. (J Endod 2008;34:76 – 887)

ey Wordsndodontics, immature permanent tooth, open apex,egenerative, revascularization, stem cell

From the *Department of Conservative Dentistry, Yonseiniversity School of Dentistry, Seoul, Korea; and †Departmentf Endodontics, University of Texas Health Science Center atan Antonio, San Antonio, Texas.

Address requests for reprints to Dr Seung-Jong Lee, De-artment of Conservative Dentistry, Yonsei University Schoolf Dentistry, 134 Shinchon-Dong, Sudaemun-Ku, Seoul, Korea20-752. E-mail address: [email protected]/$0 - see front matter

Copyright © 2008 American Association of Endodontists.oi:10.1016/j.joen.2008.03.023

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76 Jung et al.

lthough contemporary nonsurgical endodontic procedures confer high degrees ofclinical success (1, 2), the root canal system is obturated with synthetic materials,

reventing any of the advantages that might ensue by regeneration of a functionalulp-dentin complex (3). This is a particular problem when treating the necrotic butmmature permanent tooth, where conventional treatment often leads to resolution ofpical periodontitis, but the tooth remains susceptible to fracture (4) as a result ofnterruption of apical and dentinal wall development. Thus, one alternative approachould be to develop and validate biologically based endodontic procedures designed to

estore a functional pulp-dentin complex.For more than 50 years, clinicians have evaluated biologically based methods to

estore a functional pulp-dentin complex in teeth with necrotic root canal systemsaused primarily by trauma or caries. Although case series from the 1960s–1970s ineneral were not successful in producing this outcome (5, 6), it should be appreciatedhat they were performed without contemporary instruments or materials and withoutnsight generated from the trauma or tissue engineering fields (7). More recent caseeports, published during the last 15 years, have demonstrated that it is possible inumans to restore a functional pulp-dentin complex in the necrotic immature perma-ent tooth (8 –13). Human histologic studies have not yet been reported, so it is notnown whether these treatments truly recapitulate the normal pulp-dentin complex.owever, these case studies provide some measure of achieving satisfactory functionalutcomes, because postoperative recalls indicate that the patient is asymptomatic, noinus tracts are present, apical periodontitis is resolved, and there is radiographicvidence of continuing thickness of dentinal walls, apical closure, or development ofoot length.

Although case series do not provide definitive evidence to support a given treat-ent modality, they do have the advantage of being conducted in actual patients and thus

rovide greater insight than preclinical studies. Moreover, the results from case seriesan be used to identify potentially important parameters that can guide the design ofuture prospective clinical trials. For example, in nearly all published case series onulpal regeneration, an effort was made to evoke an intracanal blood clot to trigger

issue ingrowth. In this case series, we report conditions in which it was not necessaryo evoke intracanal bleeding to have continued root development.

Pulp Regeneration without Formation of a Blood Clotase 1

A 10-year-old girl was referred to the Department of Conservative Dentistry of theental Hospital of Yonsei University by an oral and maxillofacial surgeon for evaluationn the right second mandibular premolar (tooth #29). The girl had a history of swellingf the right mandibular buccal vestibule, for which she received an incision for drainagerocedure at the Department of Oral and Maxillofacial Surgery 2 months earlier. Onlinical examination, the patient was slightly symptomatic to percussion, and a sinusract was present that traced to the apex of tooth #29. The first and second premolarsere free of caries, but a fracture of an occlusal tubercle of tooth #29 was noted on

isual inspection. Periodontal probings were within normal limits for all teeth in theower right region. Diagnostic testing was inconclusive on cold and electric pulp testing,ut the patient reported sensitivity to percussion or palpation. Periradicular radio-raphic examination revealed that tooth #29 had an incompletely developed apex andperiradicular radiolucency (Fig. 1A). The diagnosis of pulp necrosis and chronic

pical abscess with a sinus tract was made for tooth #29.

JOE — Volume 34, Number 7, July 2008

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Case Report/Clinical Techniques

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igure 1. (A) Radiographic image showing an incompletely developed apex and a periradicular radiolucency of tooth #29. Note the sinus tract that traces to the apexf tooth #29. (B) Radiographic view presenting a gutta-percha cone tracing to tooth #29, and a periradicular radiolucency associated with tooth #28. (C) Radiographrom 60-day follow-up visit after both teeth were medicated with triantibiotic paste. The sinus tract is still traced to the apex of tooth #29. The thickness of temporaryilling material does not seem to be appropriate for both teeth. (D) The radiograph demonstrating complete resolution of the radiolucency and continued development

f the apex of both teeth at 6-month follow-up. (E) Follow-up at 5 years.

OE — Volume 34, Number 7, July 2008 Biologically Based Treatment of Immature Permanent Teeth with Pulpal Necrosis 877

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When the access cavity was made under rubber dam isolation, aurulent hemorrhagic exudate discharged from the canal. The toothas left open until the discharge of the exudate had stopped. After

he exudate had almost stopped, a K-file was inserted into the canal.he patient did not complain of any sensation until the file tip was in theiddle part of the canal. In addition, a little resistance by residual tissueas felt in the mid-portion of the canal, and the patient had a sensationf pain at that time. On the basis of these findings, the possibility wasaised that at least some vital pulp tissue remained in the canal, andherefore we used a method similar to that reported by Iwaya et al. (8)n an attempt to achieve regeneration of the pulp tissue complex. Theoot canal was irrigated with 5% NaOCl for 10 minutes and dried withaper points, and a mixture of ciprofloxacin, metronidazole, and mi-ocycline paste as described by Hoshino et al. (14) was introduced intohe canal with a lentulo spiral. The access cavity was closed with CavitonGC, Aichi, Japan). No mechanical instrumentation was performed dur-ng the procedure.

The patient returned a week later, asymptomatic, reporting noain postoperatively. However, the sinus tract was still present. Theccess cavity was opened, and the root canal was slowly flushed with 10L of 5.25% NaOCl, and irrigation was continued for 15 minutes. Unlike

he first visit, a mixture of erythromycin and Ca(OH)2 was placed intohe root canal. The patient returned 2 weeks later. The sinus tract wastill present, and the patient complained of slight discomfort in tooth28. A size #30 gutta-percha cone was threaded into the opening of theinus tract, and a periapical radiograph was taken. Radiographic exam-nation showed that a sinus tract was traced to the apex of tooth #29, andperiradicular radiolucency was suspected around tooth #28 (Fig. 1B).he clinical examination revealed that moderate percussion pain wasssociated with teeth #28 and #29. Diagnostic testing was inconclusiven cold and electric pulp testing on tooth #28. A diagnosis of pulpecrosis and chronic apical periodontitis was made for tooth #28.

An access cavity was made on tooth #28, and the necrotic nature ofhe upper part of the root canal was confirmed. However, some vitalulp tissue seemed to remain in the apical part of the canal becausensertion of a K-file to this point evoked a sensation of pain and someleeding. The root canal was slowly flushed with 10 mL of 5.25% NaOClnd irrigated with the same solution for 15 minutes. The same proce-ure was performed on tooth #29. Both teeth were medicated with theriantibiotic paste described by Hoshino et al. (14).

The patient returned 10 days later. The pain intensity had beeneduced, and the sinus tract was not present. To conduct a more de-ailed evaluation of the patient, the next appointment was made 2 weeksater. However, the patient failed to return for the appointment. Theatient returned 50 days later, complaining of the reappearance of theinus tract and spontaneous pain. The sinus tract was traced to the apexf tooth #29, and both teeth (teeth #28 and #29) were tender to per-ussion. The temporary filling material appeared to be intact, but theadiograph revealed the thickness of the material was not appropriateor both teeth (Fig. 1C). Because microleakage was a possibility, theanal disinfection was repeated as before. A week later, the patienteturned, and the sinus tract was closed. The canal was reirrigated withaOCl, and Ca(OH)2 paste (Vitapex; Neo Dental Chemical Products,okyo, Japan) was placed, followed by Caviton temporary restoration.

At the 6-month recall, the patient was asymptomatic. The radio-raph showed complete resolution of the radiolucency, and continuedevelopment of the apex was also observed (Fig. 1D). After removal of

he Caviton and Ca(OH)2 paste, calcific barriers were evident in botheeth by intracanal exploration with a #30 F-file. Permanent gutta-per-ha fillings were performed with Obtura (Obtura Corporation, Fenton,

O) and Sealapex (Kerr Co, Romulus, MI) followed by a bonded resin w

78 Jung et al.

estoration. At the 5-year follow-up, the patient continued to be asymp-omatic, and closure of the apex and thickening of the dentinal wallsere obvious in both teeth (Fig. 1E).

ase 2A 10-year-old boy was referred to the Department of Conservative

entistry of the Dental Hospital of Yonsei University for evaluation ofooth #29. The boy had reported slight discomfort in the lower rightegion for 1 month, but he was asymptomatic during the examinationisit. On clinical examination, a sinus tract was present that traced to thepex of tooth #29. The tooth was free of caries, but fracture of thecclusal tubercle was noted on visual inspection. Diagnostic testing was

nconclusive on cold and electric pulp testing, with sensitivity noted afterercussion or palpation. The periodontal probings were within normal

imits for the tooth. Periradicular radiographic examination revealedhat tooth #29 had an incomplete apex and a periradicular radiolucencyFig. 2A). The diagnosis of pulp necrosis and chronic apical abscessith a sinus tract was made for tooth #29.

When the access cavity was made, a purulent hemorrhagic exudateischarged from the access opening (Fig. 2B). After the control of thelood exudate with saline irrigation, there appeared to be some remain-

ng soft tissue in the root canal. The same regenerative technique mod-fied from Iwaya et al. (8) and used in Case 1 was repeated for thisatient. The root canal was irrigated with 5.25% NaOCl and replacedvery 5 minutes for a total of 30 minutes. A mixture of ciprofloxacin,etronidazole, and minocycline paste was placed into the root canalith a lentulo spiral, and the access cavity was closed with Caviton.

The patient returned 11 days later. The patient was asymptomatic,nd the sinus tract was resolved. The root canal was slowly flushed with0 mL of 5.25% NaOCl and continuously irrigated with the same solu-

ion for 15 minutes. The root canal was dried with paper points, andineral trioxide aggregate (MTA) (Dentsply Tulsa Dental, Tulsa, OK)as carefully placed over the tissue in the root canal followed by inter-ediate restorative material (IRM) (Caulk Dentsply, Milford, DE) (Fig.

C). A radiograph taken 3 months after MTA placement revealed a slightncrease of the thickness of the root canal wall and continued develop-

ent of the apex (Fig. 2D). The IRM was replaced with a bonded resinestoration. At the 2-year follow-up, the patient continued to be asymp-omatic, and closure of the apex and thickening of the dentinal wallsere obvious (Fig. 2E).

ase 3A 10-year-old boy was referred for evaluation and treatment of the

eft mandibular second premolar (tooth #20). The patient reported ahrobbing pain in the lower left region for the preceding 10 days. Theatient’s dentist had treated tooth #20 because of the presence of swell-

ng around the tooth. Drainage was established by occlusal access andncising the buccal vestibule a day before our examination. At the time ofur examination, the tooth was moderately tender to percussion, and

he canal remained open with a cotton pellet and therefore exposed tohe oral environment. A fluctuant swelling was present in the lingualttached gingiva of the tooth, and the incision line on the buccal vesti-ule also remained (Fig. 3A). A periodontal examination revealed prob-

ng depths of 3 mm or less. Radiographic examination showed a perira-icular radiolucency (Fig. 3B).

After rubber dam isolation, the cotton pellet was removed. Slightleeding was evident from the canal, and there seemed to be some vital

issue remaining in the apical half of the canal because insertion of a-file evoked a sensation of pain. The root canal was irrigated with 5%odium hypochlorite replaced every 5 minutes for a 30-minute period.hen a mixture of ciprofloxacin, metronidazole, and minocycline paste

as introduced into the canal via a lentulo spiral.

JOE — Volume 34, Number 7, July 2008

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igure 2. (A) Radiographic image showing an incompletely developed apex and a periradicular radiolucency of tooth #29. Note the sinus tract that traces to the apexf tooth #29. (B) Photograph of a purulent hemorrhagic exudate discharged from tooth #29. (C) Radiograph presenting the placement of MTA. (D) 3-month recalladiograph. A slight increase of the thickness of the root canal wall and continued development of the apex are observed. (E) Two-year radiograph showing continued

oot development.

OE — Volume 34, Number 7, July 2008 Biologically Based Treatment of Immature Permanent Teeth with Pulpal Necrosis 879

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igure 3. (A) Photograph demonstrating a fluctuant swelling in the lingual attached gingiva of tooth #20. (B) Radiograph showing a periradicular radiolucencyssociated with tooth #20. Note that the canal has remained open and therefore exposed to the oral environment. (C) Radiograph presenting the placement of MTAnd IRM. (D) Radiograph demonstrating a slight increase of the thickness of the root canal wall and the formation of dentin bridge under MTA at 2-month follow-up.

E) Ten-month radiograph showing complete resolution of the radiolucency and continued development of the apex.

80 Jung et al. JOE — Volume 34, Number 7, July 2008

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The patient returned 30 days later. The patient was asymptom-tic, and the sinus tract was resolved. However, when we removedhe intracanal dressing material, a slight amount of bleeding wasbserved. The root canal was irrigated with 5% NaOCl for 30 min-tes. Ca(OH)2 paste was placed into the canal. The patient returned0 days later. The patient was asymptomatic, and the radiographhowed resolution of the radiolucency. After rubber dam isolation,he root canal was slowly flushed with 10 mL of 5.25% NaOCl andrrigated with same solution for 15 minutes. The root canal wasried with paper points, and MTA was carefully placed over the

issue in the root canal followed by IRM (Fig. 3C). A radiographaken 2 months after MTA placement showed that a slight increase ofhe thickness of the root canal wall and a mineralized bridge ap-eared to develop beneath the MTA (Fig. 3D). At the 10-monthollow-up, the patient continued to be asymptomatic, and continued

igure 4. (A) Radiographic illustrating a large periapical radiolucency associatRM. (C) Two-month radiograph revealing some reduction in the periapical

ollow-up.

OE — Volume 34, Number 7, July 2008 Biolo

evelopment of the apex was also observed. The IRM was replacedith a bonded resin restoration (Fig. 3E).

ase 4A 13-year-old boy was referred for evaluation and treatment of the

eft second premolar. Before the visit to our clinic, the patient reportedmoderate pain in the lower left region and sought dental care in a locallinic. The patient’s dentist at the local clinic thought the pain originatedrom the necrotic pulp of tooth #20 and started the root canal treatmentithout local anesthesia. The dentist informed us that when he opened

he pulp chamber, active hemorrhagic exudate discharged from theanal. He tried to negotiate the distal canal but failed. At the time of ourxamination, the tooth was asymptomatic and remained sealed withemporary filling material. Clinical examination revealed periodontalrobings �3 mm for the tooth, and an abnormal finding such as a sinus

h the apex of tooth #20. (B) Radiograph presenting the placement of MTA andcency. (D) Radiograph demonstrating excellent periapical healing at 2-year

ed witradiolu

gically Based Treatment of Immature Permanent Teeth with Pulpal Necrosis 881

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ract was not found. Periradicular radiographic examination revealedhat tooth #20 had a bifurcated apex and a periradicular radiolucency0 mm in diameter (Fig. 4A). When we removed the temporary fillingaterial and observed the root canal system with an operating micro-

cope, some tissue was found in apical third of the root canal. Copiousrrigation was performed with 5.25% NaOCl for 30 minutes, and a

ixture of ciprofloxacin, metronidazole, and minocycline paste waslaced into the canal with a lentulo spiral. The patient returned 2 weeksater and reported no postoperative pain. After rubber dam isolation,he root canal system was slowly flushed with 10 mL of 5.25% NaOCl andrrigated with the same solution for 15 minutes. The root canal wasried with paper points, and MTA was carefully placed over the tissue inhe root canal followed by IRM (Fig. 4B). A radiograph taken 2 monthsfter MTA placement showed that some reduction in the radiolucencyas evident (Fig. 4C). At the 2-year follow-up, the radiograph showedomplete resolution of the radiolucency (Fig. 4D).

Pulp Regeneration after Formation of a IntracanalBlood Clot

ase 5A 10-year-old girl experienced painful symptoms in her mandib-

lar left second premolar that required evaluation and treatment. Herentist informed her parents that there was a large cavity in the tooth.oot canal treatment was initiated, but she did not return to the locallinic at the next appointment. Instead, she presented at our clinic forompletion of treatment of the tooth approximately 3 months later. Theanal had remained open and exposed to the oral environment, but theooth was asymptomatic. The periodontal probings were �3 mm, andn abnormal finding such as a sinus tract was not observed. A radio-raph revealed a periradicular radiolucency around the incompletelyormed apex of tooth #20 (Fig. 5A). To prevent leakage during thereatment or interappointment period, the tooth was restored with aonded resin restoration.

One week later, the tooth was isolated, and an access cavity was made.K-file was introduced into the canal until the patient felt some sensitivity,

nd a radiograph was taken (Fig. 5B). No tactile resistance was met with the-file until the patient reported sensitivity. Copious irrigation was performedith 2.5% NaOCl for 30 minutes, and a mixture of ciprofloxacin, metroni-azole, and minocycline paste was placed into the canal.

The patient returned a week later and reported no further experi-nce of pain. The root canal was slowly flushed with 10 mL of 2.5%aOCl, and irrigation was maintained with same solution for 15 min-tes. A size #30 K-file was used to irritate the tissue gently to create someleeding into the canal. The bleeding was left for 15 minutes so that thelood would clot. MTA was carefully placed over the blood clot followedy a wet cotton pellet and Caviton (Fig. 5C). Two weeks later, the patienteturned, asymptomatic, and the Caviton and cotton pellet were re-laced with a bonded resin restoration. At the 12-month recall, theatient was asymptomatic, and the radiograph showed complete reso-ution of the radiolucency, and the canal space occupied by blood clotas narrowed (Fig. 5D). At the 24-month follow-up, the patient contin-ed to be asymptomatic, and continued thickening of the dentinal wallsas obvious after radiographic examination (Fig. 5E).

ase 6A 9-year-old girl was referred for evaluation and treatment of the

andibular left second premolar. The child had a lingual swelling of theeft mandibular area for 1 week before the appointment. On clinicalxamination, the patient was asymptomatic, and the tooth appearedntact without evidence of caries. The tooth had an open apex associated

ith a large radiolucency, and a lingual sinus tract was present that s

82 Jung et al.

raced to the apex of tooth #20 (Fig. 6A). Periodontal probings were �3m for all teeth in the lower left region. Diagnostic testing was incon-

lusive with cold and electric pulp testing, but sensitivity was reportedfter percussion or palpation. The tooth was isolated, and a purulentemorrhagic exudate discharged from the canal was evident when theccess cavity was made. The root canal system was irrigated with 2.5%aOCl for 30 minutes, the canals were then dried, and a mixture ofiprofloxacin, metronidazole, and minocycline paste was placed by us-ng a lentulo spiral. The patient returned a week later and denied aistory of postoperative pain. The root canal was slowly flushed with 10L of 2.5% NaOCl. To evaluate whether vital tissue presented in the root

anal, a size #100 gutta-percha cone was introduced into the canalntil the patient reported some sensitivity. A radiograph was takennd revealed that it had reached the open apex of the tooth (Fig. 6B).ecause the presence of an open apex and thin dentinal walls greatly

ncrease the risk of future fracture, the regenerative technique as de-cribed in Case #5 was performed. A size #30 K-file was used to irritatehe tissue gently to create some bleeding into the canal. The bleedingas left for 15 minutes to permit blood clotting. MTA was carefullylaced over the blood clot. However, the blood clot was so fragile thatome of MTA extruded into the apical third of the canal (Fig. 6C). Twoeeks later, the patient returned, asymptomatic, and the Caviton andotton pellet were replaced with a bonded resin restoration. At the-month recall, the patient was asymptomatic, and the radiographhowed complete resolution of the radiolucency, with some continuedevelopment of the apex detected (Fig. 6D). At the 24-month follow-up,

he patient continued to be asymptomatic. Although the presence ofxtruded MTA was observed, it was evident that the dentinal walls dis-layed continued thickening with closure of the apex (Fig. 6E).

ase 7A 14-year-old girl was referred for evaluation on the lower right sec-

nd premolar. The girl had a history of swelling of the right mandibularuccal vestibule, for which she received an incision for drainage at the locallinic a week earlier. At the time of our examination, the tooth had an openpex associated with a radiolucency, and a buccal sinus tract was presenthat traced to the apex of tooth #29 (Fig. 7A). Periodontal probings wereithin normal limits for all teeth in the lower right region.

The tooth was isolated, an access cavity was made, copious irriga-ion with 2.5% NaOCl was continued for 30 minutes, and an aqueous

ixture of Ca(OH)2 was placed into the canal. A week later, the patienteturned, asymptomatic, and the sinus tract was resolved. The rootanal was slowly flushed with 10 mL of 2.5% NaOCl. To evaluate whetherital tissue presented in the root canal, a size #100 gutta-percha coneas introduced into the canal until the patient reported some sensation.radiograph was taken at that point and revealed that the sensation wasnly felt when the gutta-percha reached the open apex (Fig. 7B). A size30 K-file was used to irritate the tissue gently to create some bleeding

nto the canal. The bleeding was left for 15 minutes so that the bloodould clot. MTA was carefully placed over the blood clot (Fig 7C).hree weeks later, the patient returned asymptomatic, and the Cavitonnd cotton pellet were replaced with a bonded resin restoration. Theatient returned 1 year later with no symptoms or sinus tract evident.adiographic examination revealed a greatly reduced periradicular ra-iolucency (Fig. 7D).

ase 8A 10-year-old girl experienced painful symptoms in her maxillary

ight second premolar that required evaluation and treatment. Her den-ist initiated the root canal treatment on the tooth, but she did not go tohe clinic at next appointment. Approximately 3 months later, she pre-

ented at our clinic for treatment of the tooth. On presentation, the canal

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igure 5. (A) Radiograph obtained approximately 3 months after the initial treatment at local clinic. A periradicular radiolucency around the incompletely formed apex of tooth20 can be seen. (B) Radiograph demonstrating a K-file can be introduced into the canal without local anesthesia. (C) Radiograph presenting the placement of MTA. The MTAas carefully placed over the blood clot followed by a wet cotton pellet and Caviton. (D) Twelve-month radiograph showing complete resolution of the radiolucency and a

alcification of the canal space occupied by blood clot. (E) Radiograph demonstrating excellent periapical healing at 2-year follow-up.

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igure 6. (A) Periapical radiograph of tooth #20 at initial presentation. A gutta-percha cone traces sinus tract to the periradicular radiolucency associated with tooth20. (B) Radiograph demonstrating a gutta-percha cone can be introduced into the canal easily without local anesthesia. (C) Radiograph presenting the placementf MTA. Note that some of MTA extruded into the apical third of the canal. (D) Six-month recall radiograph. The radiolucency has completely disappeared, and

ontinued root development can be seen. (E) Radiograph demonstrating thickening of the dentinal walls and closure of the apex at 2-year follow-up.

84 Jung et al. JOE — Volume 34, Number 7, July 2008

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as open to the oral environment, but the tooth was asymptomatic. Theeriodontal probings were within normal limits, and an abnormal find-ng such as a sinus tract was not found. A radiograph showed that aeriradicular radiolucency was evident around the incompletelyormed apex of the tooth (Fig. 8A). The tooth was isolated, an accessavity was made, copious irrigation was done with 2.5% NaOCl for 30inutes, and a mixture of ciprofloxacin, metronidazole, and minocy-

line paste was placed into the canal. At the next appointment (3 weeksater), the root canal was slowly flushed with 10 mL of 2.5% NaOCl andontinuously irrigated with the same solution for 15 minutes under theubber dam isolation. A size #30 K-file was used to irritate the tissueently to create some bleeding into the canal, but we failed to achieveufficient blood clot to support the MTA filling. Therefore, we used

igure 7. (A) Periapical radiograph of tooth #29 at initial presentation. A gutta-p29. (B) Radiograph demonstrating a gutta-percha cone can be introduced intf MTA. The MTA was carefully placed over the blood clot followed by a wetadiolucency at 1-year follow-up.

ollatape (Sulzer Dental Inc, Plainsboro, NJ) as a matrix for the growth o

OE — Volume 34, Number 7, July 2008 Biolo

f new tissue into the pulp space. Under the microscope, we couldbserve that blood was oozing from the periradicular tissue and wetting

he Collatape. MTA was carefully placed over the Collatape followed bywet cotton pellet and Caviton (Fig. 8B). A month later, the patient

eturned, asymptomatic, and the Caviton and cotton pellet were re-laced with a bonded resin restoration. At the 17-month recall, theatient was asymptomatic, and the radiograph showed complete reso-

ution of the radiolucency with continued apical closure (Fig. 8C).

DiscussionThis case series described the outcomes of 8 patients who pre-

ented with 9 immature permanent teeth with apical periodontitis. Most

cone traces sinus tract to the periradicular radiolucency associated with toothanal easily without local anesthesia. (C) Radiograph presenting the placementpellet and Caviton. (D) Radiograph demonstrating a reduced periradicular

erchao the ccotton

f these cases were associated with a dens evaginatus, where the thin

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cclusal tubercle might often fracture, predisposing the tooth to bacte-ial infection and pulpal necrosis (15). The results indicated that it isossible to treat the necrotic and immature permanent tooth, leading topostoperative patient who is asymptomatic without evidence of a sinus

ract and a permanent tooth where apical periodontitis is resolved, andhere is radiographic evidence of continuing thickness of dentinal walls,pical closure, or further development of root length. This biologicesult is remarkable, given the typically poor prognosis of theseases (4) and the fact that contemporary treatment approachesncluding the use of MTA as an apical plug preclude further rootevelopment (16).

In the first 4 patients, treatment was administered without an at-empt to trigger bleeding and the formation of an intracanal clot. It isnteresting to note that all 5 teeth had a preoperative diagnosis of pulpal

igure 8. (A) Radiograph obtained approximately 3 months after the initial trepex of tooth #4 can be seen. (B) Radiograph presenting the placement of MTaviton. (C) Radiograph showing complete resolution of the radiolucency with

ecrosis, and this was supported both by the clinical presentation (all t

86 Jung et al.

ases had a periradicular radiolucency, and cases #1–#3 had either ainus tract or an intraoral swelling) and by the lack of pain duringccess without local anesthesia. The lack of responsiveness to cold andlectrical testing was not considered in the diagnosis, given the incom-lete nature of the tooth development (17). Despite these preoperativeiagnoses, some vitality was noted during treatment either by sensitivity

o instrumentation within the root canal system or by the visual or tactileerception of soft tissue remaining within the root canal system. Theseases were treated by NaOCl irrigation followed by at least 1-week place-ent of the triple antibiotic mixture of ciprofloxacin, metronidazole,

nd minocycline, although case #1 did require additional treatment toesolve the sinus tract. The postoperative recall periods of 10onths–5 years indicated increased thickening of the dentinal walls

nd continual apical closure. Because at least some residual vital

t at local clinic. A periradicular radiolucency around the incompletely formedMTA was carefully placed over Collatape followed by a wet cotton pellet and

nued apical closure at 17-month follow-up.

atmenA. The

issue was believed to be present, these 4 cases could be classified as

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pexogenesis, although it is not clear whether the continued apicalevelopment was due to cells in the surviving pulp-dentin complexr to regenerated tissues originating from stem/progenitor cells

ocated in the apical papilla (18).In the second set of 4 patients, treatment was administered as

bove, with the addition of evoking an intracanal blood clot. These casesre distinct from the first set of 4 cases by the lack of evidence of residualital pulp tissue within the root canal system. The initiation of the bloodlot is thought to provide a fibrin scaffold with platelet-derived growthactors that promotes regeneration of tissue within the root canal system9, 19). The clinical outcomes of 3 cases (cases #5, #6, and #8) are veryimilar to those observed in the first set of 4 patients, with 3 asymptom-tic patients returning for postoperative recall periods of 17 months–2ears and radiographic evidence of increased thickening of the dentinalalls and continual apical closure. Case #7 showed some different clinicalutcomes. Although apical periodontitis was resolved in the case, aarrowing of the canal space was not significant at 1-year follow-up.

Although the clinical outcomes of most cases were consistent withhe hypothesis of a functional restoration of biologic root development,he precise mechanisms and cellular source remain unknown. It haseen suggested that the radiographic evidence of increased root thick-ess might be due to ingrowth of dentin, cementum, or bone (13, 19).he present findings do not distinguish among these possibilities. We doote that other investigators have published human histologic stud-

es describing tissue changes in the pulp-dentin complex or peri-dontium after tooth extraction after various dental treatments (5,0 –22). Although this approach is clearly subject to considerablethical issues, including informed consent and strict inclusion cri-eria, human histologic studies would directly answer the questionf tissue identity after pulpal regeneration/revascularization proce-ures in patients.

The value of case reports is the demonstration of what is possiblen our patients. Reports from astute clinical practitioners have playedivotal roles in advancing dental therapeutics including recognition ofhe properties of fluoride (23), as well as the adverse effects of bisphos-honates (24). The present study, combined with prior reports onegeneration/revascularization of the nonvital immature permanentooth (8 –13), constitute a growing case series suggesting that biologi-ally based treatment approaches might be of particular value in restor-ng root development and apical closure in these otherwise difficultases. Importantly, the value of prospective randomized clinical tri-ls is their ability to provide strong quantitative evidence for bothreatment efficacy and the potential for adverse effects. This growingody of case reports provides impetus for developing prospectiveandomized controlled trials evaluating these methods. Finally, ifhis biologic process can occur in the immature tooth, then it also

ight provide some insight into the conditions necessary to regen-rate a functional pulp-dentin complex in the nonvital fully formed

ermanent tooth.

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