Redefining ‘Success’ With Regenerative Endo by Drs. Judy McIntyre and Nikhil Mallick

2 specialists share cases

by Drs. Judy McIntyre and Nikhil Mallick

One of the recurring hot topics during residency was success: How do you define treatment success? While most dentists would agree that endodontic treatment success results in the prevention or reversal of apical periodontitis/bone loss and symptoms, with trauma and children’s development “the definition of success must change,” as esteemed endodontist and trauma expert Dr. Martin Trope often says.

Historically, in cases of caries, trauma or congenital anomalies, pulp necrosis of an immature tooth has required an apexification procedure, which involves placement of an apical barrier and then subsequent obturation.^1–3 In these cases, the level of development at the time of pulp necrosis often results in short, thin, weak dentinal-root walls, which can be prone to fracture later.^1–3 Further, in terms of endodontic treatment, apexification has less predictability and control of disinfecting an “open” environment and is more challenging, compared with the closed root system and conventional endodontics.^1–3

While traditional endodontic therapy involves disinfection, debridement and subsequent obturation of the root canal system with biologically inert material, the goal of regeneration is for the body to replace functional, live tissue within the diseased system.^1–3 Regenerative endodontics or “regeneration” (previous terminology has also included “revascularization”) implements biologically based procedures to form new tooth structure and replace that which has become necrotic.² Additional benefits of achieving this goal are continued root development and/or apical closure (root end development) and, ultimately, avoiding “traditional” root canal therapy.

Hence, the regenerative procedure is the ultimate “endodontic” procedure when successful: regeneration of the pulp with root end closure, as well as healing/absence of any periapical pathology and symptoms requiring no further treatment. However, if signs or symptoms of disease or necrosis of the new pulp/pulplike tissue occurs, any additional apical closure from the regenerative endodontic procedure can promote a more predictable outcome, should root canal therapy later be required. Therefore, even “unsuccessful” regeneration can still be beneficial as any progress from the initial immature apex state must be acknowledged as a victory.

Case 1: Dr. Judy McIntyre
A 7-year-old boy avulsed UR1 and UL1 while playing baseball during the summer of 2004; the teeth were reimplanted (Figs. 1a–1c) and splinted, but underwent pulp necrosis. Both teeth were disinfected with triple antibiotic paste in preparation for revascularization/pulpal regeneration. Blood clot formation was provoked and, in both teeth, the coagulum came up to approximately the cementoenamel junction (CEJ) in both teeth. Mineral trioxide aggregate (MTA) was placed over the clot, with intermediate restorative material (IRM) to close the access opening (Fig. 2), and we hoped for the best: regeneration. During a period of observation over several months, we took a radiograph and interpreted some hard tissue formation (Fig. 2).

One night five months after the initial avulsions, the patient fell out of bed and reavulsed UL1! Once again, we replanted UL1 and MTA was placed in the open apex extraorally (Fig. 3), held by the clinical crown and with continuous saline being dispensed over the root’s periodontal ligament (PDL). Seven months later, we observed minimal radiographic changes (Figs. 4a and 4b). In the fall of 2005, under rubber dam isolation from an orthograde approach, the canal was irrigated and dried, sealer was applied and the canal was backfilled with warm gutta percha (Figs. 5a–5c).

In early 2006, UR1—not the one that was reavulsed—showed early radiographic resorption (Figs. 6a–6d—note the amount of MTA is less dense). UL1 appeared intact without signs of resorption. By this time, the child had grown, with UL1 and UR1 and the adjacent teeth had moved in coordination with maxillary growth: This should be regarded as a success. Retention of these teeth allowed for the maxilla to continue its three-dimensional growth without any atrophy or alveolar defects.

After graduating from residency in summer 2006, I was hopeful that all things ended well for the patient dentally. Recently I discovered that in the fall of 2006, the patient returned to the clinic. Both UR1 and UL1 had undergone ankylosis and replacement resorption (Fig. 7), As is common in ankylosis cases, he was monitored. In summer 2007, radiographic signs of continued anklyosis were noted (Fig. 8). More than a year later (Fig. 9), discussion began for an alternative treatment of decoronation: a wonderful treatment option for ankylosed teeth.^4,5 In early 2009, the patient underwent decoronation for both teeth at age 12, which allowed him to retain the clinical crowns of both teeth with continued alveolar presence (Fig. 10).

The attempted regenerative endodontic procedures maintained these teeth in situ for an additional five years. The valuable bone that was gained from those five years of growth will surely be beneficial for subsequent implant replacement when his growth is complete. This should still be considered a success even though the final outcome was not what was initially intended. Several years of additional bone growth are valuable, especially compared with the alternative: premature tooth loss and bone atrophy.

Fig. 1A

Fig. 1B

Fig. 1C

Fig. 2

Fig. 3

Fig. 4A

Fig. 4B

Fig. 5A

Fig. 5B

Fig. 5C

Fig. 6A

Fig. 6B

Fig. 6C

Fig. 6D

Case 2: Dr. Nikhil Mallick
In 2015, a 9-year-old girl presented with a complaint of a bubble on her gums. She had no pain, but she and her mother were concerned because they had been told by their pediatric dentist about an infection. A clinical exam showed a sinus tract that traced to the apex of tooth UR1, which had an incisal edge composite (Figs. 11 and 12). Upon questioning, a history of trauma one or two years previously was reported, with no subsequent symptoms or treatment other than the composite repair.

In contrast to the development of UL1, the pulp in UR1 appears to have become necrotic soon after the trauma. With the wide-open, divergent apex and level of root immaturity, pulp regeneration seemed to be the most desirable option. This was undertaken using diluted sodium hypochlorite and calcium hydroxide medicament at the first visit and 17% ethylenediaminetetraacetic acid (EDTA) at the second visit. The sinus tract healed between visits. A clot was induced and Biodentine from Septodont was used as the material against the scaffold. A composite restoration was eventually placed and the patient was monitored at regular intervals (Fig. 13).

Over the next two or three years, the periapical pathosis healed, which is the first goal for regeneration. However, the second goal of further root development—root wall thickening and closure—did not occur; rather, a radiopaque, hard tissue formation developed both in the apical third of the canal and toward the apical opening (Fig. 14).

In 2019, at a regular recall visit, a sinus tract was once again present in the apical area. The sinus tract traced to the apex of UR1, where periapical pathosis had recurred

(Figs. 15 and 16). No recurrent decay was observed, and no history of further trauma was reported. Treatment options were discussed, and re-treatment with the goal of apexification with a resin buildup was recommended and decided upon. Ree and Schwartz reported a 96% healing rate with this method in immature incisors over a 5- to 15-year time period.⁶

At the initial visit, the intact composite and Biodentine, which was discolored and soft, were removed, and the canal was irrigated with diluted sodium hypochlorite. The osteoid material was removed with Munce burs and the canal packed with calcium hydroxide for two months (Fig. 17). At the second visit, the sinus tract had healed and the patient remained asymptomatic. The canal was irrigated with diluted sodium hypochlorite and dried. A collagen barrier was placed and MTA apexification was completed

(Fig. 18). A small layer of thermoplasticized gutta percha was placed with sealer as a barrier over the MTA, and a fiber post/resin buildup was completed. Because of the large size of the canal, multiple EndoSequence fiber posts were placed passively with the buildup (Figs. 19 and 20).

Long-term prognosis after trauma is guarded, varies with the severity of trauma and relies upon proper management. In this case, regeneration was a great first option and, even with the less-than-ideal outcome, allowed us to perform re-treatment with apexification as a second option.⁶

The goal of traumatic injuries is obviously long-term success, but a truly successful outcome in many cases is maintenance of the tooth and its surrounding bone without symptoms or pathology until skeletal development is complete. We’re hopeful! 

Fig. 7

Fig. 8

Fig. 9

Fig. 10

Fig. 11

Fig. 12

Fig. 13

Fig. 14

Fig. 15

Fig. 16

Fig. 17

Fig. 18

Fig. 19

Fig. 20

Discussion
For regeneration, the existing cells of the body are stimulated to regrow missing tissue. Stem cells, remaining hematologic components, tissue scaffolds, collagen matrixes, growth factors and other ingredients that can be introduced into the root canal system have been found to be useful adjuncts for pulpal regeneration or additional root development.^2,3,7–9

In previous pulp regeneration protocols (circa 2004), the immature, necrotic canal was irrigated, then disinfected using Hoshino’s triple antibiotic paste¹⁰ containing ciprofloxacin, metronidazole and minocycline in the ratio of 1:1:1. At the second appointment several weeks later, the medicament was irrigated out by either diluted sodium hypochlorite (as in Case 1) or, more recently, sterile saline irrigation.¹¹ The periapical tissue was stimulated with a sterile K file (size 50+) to promote a blood clot with the goal of it reaching the CEJ, which is not always possible. MTA was placed over the blood clot, but apical to the CEJ. IRM or a bonded composite was placed over the MTA.^11,12

The protocol changed, favoring calcium hydroxide as the intracanal medicament^2,9,10,12,13 instead of Hoshino’s triple antibiotic paste. This was still followed by blood clot stimulation, augmented by the addition of an intracanal collagen scaffold to bring it up to the CEJ.^3,9 Use of local anesthetic has also been controversial. The regenerative procedure may be hindered by epinephrine in local anesthetic, resulting in vasoconstriction that limits hemorrhage from the periapical tissue and clot formation within the canal. The use of local anesthetics without added vasoconstrictor is recommended.¹²

Currently, the regenerative endodontic protocol^8,12 recommends minimal or no instrumentation of the canal, relying solely on thorough irrigation of the canal system. The disinfection is augmented with intracanal medication—either calcium hydroxide or triple antibiotic paste—between appointments. The treated tooth is subsequently sealed with MTA and glass ionomer/resin cement at the completion of the treatment. Periodical follow-ups are strongly recommended to observe continued maturation of the root.⁸ Conversely, if disease or symptoms develop, close monitoring and follow-ups are required so that timely intervention and alternative treatment methods can be offered swiftly to minimize undesired sequelae.

During the American Association of Endodontists 2019 annual session in Montreal, Dr. Anibal Diogenes¹³ stated that more recent research has shifted back to using triple antibiotic paste for intracanal disinfection. Some colleagues are still using calcium hydroxide for regenerative endodontic procedures, as per Diogenes at a previous AAE annual session. Some practitioners irrigate with diluted sodium hypochlorite for these cases (1:4, making 1.05% sodium hypochlorite irrigant) instead of saline. EDTA has also been recommended to allow release of growth factors sequestered in the dentin.^3,9,12 A thorough review of regeneration and both protocols in detail can be found in the Namour, Theys 2014 publication.¹³

In both of the presented cases, regeneration of vital tissue into the necrotic infected pulp spaces of immature permanent maxillary incisors was attempted in vivo by stimulation of the periapical tissues to create a blood clot scaffold in the canal space. The ideal outcome of successful pulp regeneration includes continued root formation until apical closure occurs, so that no further treatment is necessary; that is the outcome and ultimate goal of “successful pulp regeneration” and what we had hoped for in both cases (all three teeth). However, both cases required early intervention and alternative treatment modalities, which should always be anticipated in regeneration cases.

In conclusion, although the outcome of regenerative endodontic procedures remains somewhat unpredictable and the clinical management of these teeth is challenging, when successful, they are a great improvement over alternative treatment modalities. Any development beyond the initial presentation of an immature tooth with a necrotic pulp should be considered a success.

References
1. Hargreaves, Kenneth M., and Cohen, Stephen, eds. (2011). Pathways of the Pulp 10th Edition. St. Louis, Missouri, US: Mosby Elsevier. p. 602–618. 
2. Hargreaves, K.M.; Diogenes, A.; Teixeira, F.B. (2013). Treatment Options: Biological Basis of Regenerative Endodontic Procedures. Pediatric Dentistry. 35 (2): 129–140.
3. Thibodeau, B., and Trope, M. Pulp Revascularization of a Necrotic Infected Immature Permanent Tooth: Case Report and Review of the Literature. Pediatr Dent. 2007 Jan-Feb; 29(1):47-50.
4. Malmgren, B. Decoronation: How, Why, and When? J Calif Dent Assoc. 2000 Nov;28(11):846-54.
5. Malmgren, B.; Tsilingaridis, G.; and Malmgren, O. Long-Term Follow-Up of 103 Ankylosed Permanent Incisors Surgically Treated With Decoronation—A Retrospective Cohort Study. Dent Traumatol. 2015 Jun; 31(3):184-9.
6. Ree M.H., and Schwartz R.S. Long-Term Success of Nonvital, Immature Permanent Incisors Treated With a Mineral Trioxide Aggregate Plug and Adhesive Restorations: A Case Series from a Private Endodontic Practice. J Endod. 2017 Aug; 43(8):1370–1377.
7. Wigler, R.; Kaufman, A.Y.; Lin, S.; Steinbock, N.; Hazan-Molina, H.; and Torneck, C.D. Revascularization: A Treatment for Permanent Teeth With Necrotic Pulp and Incomplete Root Development. J Endod. 2013 Mar; 39(3):319-26.
8. Huang, G.T. A Paradigm Shift in Endodontic Management of Immature Teeth: Conservation of Stem Cells for Regeneration. J Dent. 2008 Jun; 36(6):379-86.
9. Yamauchi, N.; Yamauchi, S.; Nagaoka, H.; Duggan, D.; Zhong, S.; Lee, S.M.; Teixeira, F.B.; and Yamauchi, M. Tissue Engineering Strategies for Immature Teeth With Apical Periodontitis. J Endod. 2011;37(3):390–7. 
10. Hoshino, E.; Kurihara-Aando, N.; Sato, I.; Uematsu, H.; Sato, M.; Kota, K., Et Al. In-Vitro Antibacterial Susceptibility of Bacteria Taken From Infected Root Dentine to a Mixture of Ciprofloxacin, Metronidazole and Minocycline. Int Endod J. 1996; 29:125–30.
11. Neelamurthy, P.S.; Kumar, R.A.; Balakrishnan, V.; Venkatesan, S.M.; and Narayan, S. Revascularization in Immature and Mature Teeth with Necrotic Pulp: A Clinical Study. J Contemp Dent Pract. 2018 Nov 1; 19(11):1393-1399.
12. Namour, M., and Theys, S. Pulp Revascularization of Immature Permanent Teeth: A Review of the Literature and a Proposal of a New Clinical Protocol. Scientific World Journal. 2014; 2014: 737503.
13. Diogenes, A.R.: Ruparel, N.B.; Teixeira, F.B.; and Hargreaves, K.M. Pulp Regeneration: Translational Science in Disinfection for Regenerative Endodontics. J Endod. 2014 Apr; 40 (4 Supp):S52-S57.

The authors wish to thank their families; the endodontics departments at the Rutgers School of Dental Medicine and the University of North Carolina at Chapel Hill; and Drs. Blayne Thibodeau, Noz Yamauchi and Peter Tawil.