Treatment outcomes of regenerative endodontics and apexification of traumatized immature necrotic permanent incisors

Introduction: Presently, calcium hydroxide (CH) apexification and mineral trioxide aggregate (MTA) apexification are the available treatments for traumatized immature necrotic teeth. Although these treatments have been available for many years, few studies have assessed these techniques for long- term survival of teeth. Recently, a new treatment modality has emerged - regenerative endodontic treatment (RET). However, RET's clinical, radiographic, and disinfection protocols need to be evaluated.

Aims: This thesis investigates the clinical, radiographical, and microbiological outcomes of regenerative endodontic treatment. In addition, this thesis investigates the long-term survival of traumatized immature necrotic teeth after the use of apexification and identifies the risk factors for premature tooth loss.

Materials and methods: This thesis includes a systematic literature review (Study I), an observational prospective cohort design (Study II), a randomized clinical trial (Study III), and a retrospective longitudinal observational cohort design (Study IV).

In Study I, five scientific databases were screened (PubMed, Web of Science, Cochrane Library, Ovid/Medline, and Embase) for intervention studies on RET and/or apexification of traumatized immature necrotic teeth. Only peer- reviewed studies with a study size of at least 20 cases with a follow-up of 24 months were included. Eligibility assessment was blinded and performed independently. Subgroup analyses were performed on three outcomes: survival, success, and continued root development.

In Study II, RET was performed on 75 traumatized necrotic immature incisors. The radiographic outcome measures were continued root formation (width and length), root resorption, apex closure, periapical index, and root development stage. The clinical outcome measures were percussion pain, palpation pain, pathological tooth mobility, swelling, sinus tract, ankylosis, crown discolouration, and subjective pain. Treatment outcomes were categorized as a success or failure based on the clinical and radiographic outcome measures.

In Study III, microbiological assessment was based on root canal samples from 41 traumatized immature necrotic teeth treated with RET where two different root canal dressing were used in a randomized order (CH and CHD). Analysis of the average bacterial load (CFU/sample) and bacterial diversity (taxa/sample) was performed at three timepoints - before root canal dressing (S2); after debridement (S); and after root canal dressing (S5).

In Study IV, records of 2400 children and adolescents were screened for presence of TDI to immature incisors where endodontic treatment with the two apexification techniques was performed between January 2003 and December 2022. These incisors were compared to a control group of mature teeth treated with conventional endodontic techniques. The following variables were studied: age, sex, apexification technique, presence of luxation and hard tissue injuries, preoperative root development stage (RDS), preoperative and postoperative periapical index (PAI), when tooth loss occurred, and overall survival time in years.

Results: Seven studies with heterogenous designs were included in the final synthesis. The included articles in Study I revealed that both regenerative and apexification techniques had equal rates of success and survival and proved to be effective in the treatment of immature necrotic permanent teeth. Regenerative endodontic techniques appeared to be superior to apexification techniques in terms of stimulation of root maturation - i.e., root wall thickening and root lengthening.

Study II revealed that RET was successful in 60% of the cases. When successful, RET presented meaningful outcomes, with a resolution of periapical infection, increased root length and width, and apex closure. Two predictive variables for continued root maturation were identified - preoperative root development stage and preoperative dentine wall thickness. The failed cases were related to lack of bleeding and persistent infections.

Study III revealed that the primary microflora were more diverse in successful cases than in failed cases. Decreases in bacterial loads and diversity/sample occurred between S2 and S3, although new increases were seen at S5 in the CHD subgroup (successful and failed) and load/sample in the CH subgroup (failed). At S5, the successful cases showed more bacterial decreases. No specific species were associated with the outcomes with no statistical differences between the disinfection efficacies.

Study IV showed that the median survival time was up to 10 years for CH apexification, 16.1 years for MTA apexification, 15.5 years for luxation injuries other than intrusions and avulsions, 12.5 years for intrusions, and 6.8 years for avulsions. The variables with significant negative impact on tooth survival were CH apexification, avulsion, and postoperative PAI of 3-5. No significant relationships were found for the variables MTA apexification, concussion, subluxation, lateral luxation, extrusion, intrusion, hard tissue injuries, preoperative RDS, preoperative PAI scores and postoperative PAI scores of 1-2. After adjustment, the risk for premature tooth loss was 13.5 times higher in CH apexification, approximately 2 to 4 times higher in PAI 3-5, and 5.6 times higher in avulsions.

Conclusion: According to the published literature, both RET and apexification techniques have equal rates of success, survival, and effectiveness in the treatment of immature necrotic permanent teeth, although only RET stimulates root maturation. Knowledge gaps were identified regarding the treatment and follow-up protocols for both techniques. When successful, RET provides satisfactory clinical and radiographical outcomes. The failed cases were related to lack of bleeding and persistent infections, indicating that new techniques are needed to improve the predictability of RET. For microbiological outcomes, there were no statistical differences in CH and CHD efficacy. After root canal dressing (S5), microflora persisted in both successful and failed outcomes, but the abundance and diversity increased significantly only in the failed cases. Compared to the failed outcomes, the successful outcomes presented higher diversity and higher decreases of the primary microflora at S5. Only the failed cases had significant increases in abundance and diversity at S5. The analysis of the long-term outcomes identified CH apexification, avulsion, and postoperative PAI of 3-5 as prognostic variables with significant negative impact on the risk for premature tooth loss.

List of scientific papers

I. What is the best long-term treatment modality for immature permanent teeth with pulp necrosis and apical periodontitis? Wikström A, Brundin M, Lopes MF, El Sayed M, Tsilingaridis G. Eur Arch Paediatr Dent. 2021;22(3):311-340 https://doi.org/10.1007/s40368-020-00575-1

II. Endodontic pulp revitalization in traumatized necrotic immature permanent incisors: Early failures and long-term outcomes - A longitudinal cohort study. Wikström A, Brundin M, Romani Vestman N, Rakhimova O, Tsilingaridis G. Int Endod J. 2022;55(6):630-645 https://doi.org/10.1111/iej.13735

III. Microbiological assessment of success and failure in pulp revitalization: A randomized clinical trial using calcium hydroxide and chlorhexidine gluconate in traumatized immature teeth. Wikström A, Romani Vestman N, Rakhimova O, Gimeno DL, Tsilingaridis G, Brundin M. J Oral Microbiol. 2024 Apr 24;16(1):2343518 https://doi.org/10.1080/20002297.2024.2343518

IV. Outcomes of apexification in immature traumatized necrotic teeth and risk factors for premature tooth loss: A 20-year longitudinal study. Wikström A, Brundin M, Mohmud A, Andersson M, Tsilingaridis G. Dent Traumatol. 2024 Dec;40(6):658-671 https://doi.org/10.1111/edt.12973