Management of Failed Regenerative Endodontic Treatment of a Necrotic Immature Molar: A Case Report With 12-Month Follow Up

Introduction: Management of necrotic immature permanent teeth has always posed a challenge to clinicians. Regenerative endodontic procedures (REPs) have been proposed as an alternative to apexification to treat necrotic immature teeth. However, few failed cases of REPs have been presented in the literature with different successful retreatment approaches. Case presentation: An eight-year-old boy reported spontaneous pain in the right permanent mandibular first molar. Regenerative endodontic treatment using platelet-rich fibrin (PRF) was the treatment method due to the open apices. At the 9-month follow-up, there was a periapical lesion around the distal root. Hence, apexification with Mineral trioxide aggregate (MTA) was carried out. In the twelve-month follow-up, the periapical lesion healed radiographically. Conclusions: MTA and bioceramic-based root canal sealers yielded satisfactory outcomes in lesion healing. Little is known about the biological and clinical aspects of regenerative endodontic treatment. Moreover, there are still unknown factors that govern the success of REPs.

This report presented a case of management of failed regenerative endodontic treatment of a necrotic immature molar using MTA apical plug and bioceramic-based root canal sealer.

Case presentation
An eight-year-old boy was presented to the Department of Pediatric Dentistry, at Damascus University, in August 2021.
He was referred to evaluate the right permanent mandibular first molar after incomplete treatment performed by a general dentist.The patient's parents reported a previous spontaneous pain lasting for hours and aggravated when the patient lay down, for which his dentist had performed an emergency treatment.The patient was with low socioeconomic status.
There was no relevant medical history.The following treatment session was appointed to be 3 weeks later.There was no tenderness to palpation or percussion.An

5
A conventional IANB was administered.After the removal of the stainless steel crown, the tooth was isolated with a rubber dam.The 2 mm thick layer of white MTA was removed with CPR ultrasonic tips (Obtura Spartan Endodontics, Algonquin, IL, USA).After WL determination (Figure 5), the distal root was slightly shaped with stainless steel K-file (Dentsply, Maillefer, Ballaigues, Switzerland), and the mesial roots were prepared using crown down technique.The canals were irrigated using 20 mL of 2.5% sodium hypochlorite solution, followed by 20 mL of sterile saline solution rinsing, then the canals were dried with sterile absorbent paper points.TAP was applied, then the tooth was sealed with a temporary restoration, and the next visit was appointed 21 days later.

Figure 5. Working length determination in the distal canal
On the next visit appointment, an IANB was administered followed by rubber dam isolation.The access cavity was reopened, and the distal root was rinsed with 20 mL of 2.5% sodium hypochlorite solution, followed by 20 mL of sterile saline solution, and then dried with absorbent paper points.
MTA apical plug was applied in small increments.At first, 30 gutta-percha cones (Dentsply, Maillefer, Ballaigues, Switzerland) were used to transfer the MTA increments into the apical third of the distal root, then finally were condensed with the aid of an endodontic plugger into a 5 mm apical plug.
A moist cotton pellet was placed over the MTA apical plug, and the tooth was sealed with a temporary restoration.
After 48 hours, an IANB was administered, the tooth was isolated, and the access cavity was reopened.The WL was determined (Figure 6).The canals were rinsed with 20 mL of 2.5% sodium hypochlorite solution, followed by 20 mL of sterile saline solution, and dried with absorbent paper points.
The mesial and distal canals were sealed with a bioceramicbased root canal sealer (CeraSeal, Meta Biomed, Chungcheongbuk-do, Korea), then GIC coronal filling was placed on the toot filling materials, and a stainless steel crown was adjusted and cemented with luting glass ionomer cement (Figure 7).In the three-month follow-up, the tooth was asymptomatic, and the periapical lesion began to resolve (Figure 8).In the six-month follow-up, the periapical lesion healed (Figure 9), and in the twelve-month follow-up, the periapical lesion fully healed (Figure 10). Figure 6.Working length determination in the mesial canals

Conclusion
The results of the present case report suggest that little is known about the biological and clinical aspects of REP, and there are many unanswered questions.Moreover, there are still unknown factors that govern the success of REP.
Therefore, further studies should be conducted with a large sample size to decipher this medical mystery.However, this approach is conservative.
inducing a calcified apical barrier in non-vital immature teeth.However, this method has several disadvantages, including multiple visits, long-term treatment, and reinfection possibilities.The previous facts suggested the use of mineral trioxide aggregate (MTA) as an alternative to calcium hydroxide [2,3], which yielded satisfactory outcomes in terms of dentin bridge formation in vital pulp therapy [3] and resolving periapical lesions [4].Unfortunately, both procedures cannot induce maturation and natural development of the root canal system.Regenerative endodontic procedures (REPs) have been proposed as a conservative alternative to apexification to treat non-vital immature teeth.REPs aim to thicken and elongate the root canal walls, induce apical closure, promote dentinpulp complex formation, and restore physiologic functions.Namely, REPs aim to mimic the cellular and molecular mechanisms during tooth maturation.This treatment method has been considered a "paradigm shift" [5].The three main ingredients for regenerative endodontic treatment are stem cells, growth factors, and scaffolds.Firstly, Stem cells can proliferate and differentiate to induce hard tissue formation.Secondly, growth factors regulate the stimulation of several apoptosis.Lastly, scaffolds serve as an extracellular matrix to support tissue ingrowth and provide correct localization for cells and can be either natural or synthetic [5,6].Platelet-rich fibrin (PRF) is a synthetic scaffold of autologous fibrin loaded with platelet cytokines, leukocyte cytokines, and bioactive molecules [6].It was first proposed in France by Choukroun et al. in 2001 [6,7].However, few failed cases of REPs have been presented in the literature with different successful retreatment approaches [8-10].

Figure 1 .
Figure 1.Diagnostic radiograph of the right permanent mandibular first molar showed the presence of periapical radiolucency with lamina dura widening.
IANB was administered followed by rubber dam isolation.The access cavity was reopened, the intracanal dressing was flushed out of the canals by sterile saline solution irrigation, then the canals were irrigated with 20 mL of 17% EDTA (EDTA Solution, Prevest DenPro®, Lewes, DE, USA).Ultimately, they were rinsed with sterile saline solution.The canals were dried with absorbent paper points.In the meantime, PRF was prepared by drawing a 5 mL sample of whole venous blood from the patient's right foramen (right median cubital vein).The collected venous blood sample was transferred into a vacutainer tube (Vacuum Blood Collection Red Top Plain Tube, Jiangsu Nuohong Medical Technology Co., Ltd., Anhui, China) without anticoagulant and centrifugated (REMI Laboratories, Mumbai, Maharashtra, India) at 3000 revolutions per minute (rpm) for 10 minutes.Three layers were obtained: an acellular plasma layer (PPP) at the top, PRF in the middle, and a red blood cells layer (RBCs) at the bottom (Figure2).A sterile tweezer was used to remove the jelly PRF from the vacutainer tube, then it was placed on a dry gauge to squeeze out the fluid present in the fibrin matrix.The freshly prepared PRF was fragmented into small increments and was inserted apically in the root canals up to the middle third and condensed using an endodontic plugger (Elite Dental Products, Daive, Florida, USA).A 2mm thick layer of white MTA (ProRoot; Dentsply Tulsa Dental Specialty, Tulsa, OK, USA) was placed on the top of the floor of the pulp chamber and then sealed with a wet cotton pellet and temporary filling (Cavit, 3M ESPE, St. Paul, MN, USA) (Figure3).On the next day, the temporary restoration and the wet cotton pellet were removed, then GIC coronal filling was placed and a stainless steel crown (3M ESPE, St. Paul, MN, USA) was adjusted and cemented with luting glass ionomer cement (GC Fuji I, Leuven, Belgium).At 3-and 6-month follow-ups, the tooth was asymptomatic, with no sensitivity to palpation or sensitivity tests.At the 9month follow-up, there was a periapical radiolucency around the distal root, tenderness to palpation and percussion, and a negative response to different vitality tests.However, the periapical lesions were resolved around the mesial canals (Figure4).Therefore, apexification with MTA was 4 considered an optimal retreatment option for the distal canal.

Figure 2 .
Figure 2. Three layers were obtained after centrifugation: an acellular plasma layer (PPP) at the top, a platelet-rich fibrin layer (PRF) in the middle, and a red blood cells layer (RBCs) at the bottom.

Figure 3 .
Figure 3. Postoperative radiograph after regenerative treatment and MTA placement.

Figure 4 .
Figure 4. Follow-up radiograph after 9 months showed a periapical lesion around the distal root and bony healing around the mesial roots.

Figure 7 .
Figure 7. Postoperative radiograph after MTA apical plug placement and sealing with bioceramic-based root canal sealer.

Figure 8 .
Figure 8. Follow-up radiograph after 3 months, the periapical lesion around the distal root began to resolve.