Regenerative endodontic treatment in avulsed immature permanent teeth: A scoping review

<p dir="ltr"><b>Introduction</b><b>:</b> 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.</p><p dir="ltr"><b>Aims</b><b>:</b> 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.</p><p dir="ltr"><b>Materials and methods:</b> 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).</p><p dir="ltr">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.</p><p dir="ltr">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.</p><p dir="ltr">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).</p><p dir="ltr">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.</p><p dir="ltr"><b>Results:</b> 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.</p><p dir="ltr">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.</p><p dir="ltr">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.</p><p dir="ltr">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.</p><p dir="ltr"><b>Conclusion:</b> 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.</p><h3>List of scientific papers</h3><p dir="ltr">I. What is the best long-term treatment modality for immature permanent teeth with pulp necrosis and apical periodontitis? <b>Wikström A,</b> Brundin M, Lopes MF, El Sayed M, Tsilingaridis G. Eur Arch Paediatr Dent. 2021;22(3):311-340 <a href="https://doi.org/10.1007/s40368-020-00575-1" rel="noreferrer" target="_blank">https://doi.org/10.1007/s40368-020-00575-1</a></p><p dir="ltr">II. Endodontic pulp revitalization in traumatized necrotic immature permanent incisors: Early failures and long-term outcomes - A longitudinal cohort study. <b>Wikström A,</b> Brundin M, Romani Vestman N, Rakhimova O, Tsilingaridis G. Int Endod J. 2022;55(6):630-645 <a href="https://doi.org/10.1111/iej.13735" target="_blank">https://doi.org/10.1111/iej.13735</a></p><p dir="ltr">III. Microbiological assessment of success and failure in pulp revitalization: A randomized clinical trial using calcium hydroxide and chlorhexidine gluconate in traumatized immature teeth. <b>Wikström A,</b> Romani Vestman N, Rakhimova O, Gimeno DL, Tsilingaridis G, Brundin M. J Oral Microbiol. 2024 Apr 24;16(1):2343518 <a href="https://doi.org/10.1080/20002297.2024.2343518" target="_blank">https://doi.org/10.1080/20002297.2024.2343518</a></p><p dir="ltr">IV. Outcomes of apexification in immature traumatized necrotic teeth and risk factors for premature tooth loss: A 20-year longitudinal study. <b>Wikström A,</b> Brundin M, Mohmud A, Andersson M, Tsilingaridis G. Dent Traumatol. 2024 Dec;40(6):658-671 <a href="https://doi.org/10.1111/edt.12973" target="_blank">https://doi.org/10.1111/edt.12973</a></p>

<p dir="ltr"><b>Introduction</b><b>:</b> 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.</p><p dir="ltr"><b>Aims</b><b>:</b> 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.</p><p dir="ltr"><b>Materials and methods:</b> 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).</p><p dir="ltr">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.</p><p dir="ltr">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.</p><p dir="ltr">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).</p><p dir="ltr">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.</p><p dir="ltr"><b>Results:</b> 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.</p><p dir="ltr">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.</p><p dir="ltr">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.</p><p dir="ltr">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.</p><p dir="ltr"><b>Conclusion:</b> 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.</p><h3>List of scientific papers</h3><p dir="ltr">I. What is the best long-term treatment modality for immature permanent teeth with pulp necrosis and apical periodontitis? <b>Wikström A,</b> Brundin M, Lopes MF, El Sayed M, Tsilingaridis G. Eur Arch Paediatr Dent. 2021;22(3):311-340 <a href="https://doi.org/10.1007/s40368-020-00575-1" rel="noreferrer" target="_blank">https://doi.org/10.1007/s40368-020-00575-1</a></p><p dir="ltr">II. Endodontic pulp revitalization in traumatized necrotic immature permanent incisors: Early failures and long-term outcomes - A longitudinal cohort study. <b>Wikström A,</b> Brundin M, Romani Vestman N, Rakhimova O, Tsilingaridis G. Int Endod J. 2022;55(6):630-645 <a href="https://doi.org/10.1111/iej.13735" target="_blank">https://doi.org/10.1111/iej.13735</a></p><p dir="ltr">III. Microbiological assessment of success and failure in pulp revitalization: A randomized clinical trial using calcium hydroxide and chlorhexidine gluconate in traumatized immature teeth. <b>Wikström A,</b> Romani Vestman N, Rakhimova O, Gimeno DL, Tsilingaridis G, Brundin M. J Oral Microbiol. 2024 Apr 24;16(1):2343518 <a href="https://doi.org/10.1080/20002297.2024.2343518" target="_blank">https://doi.org/10.1080/20002297.2024.2343518</a></p><p dir="ltr">IV. Outcomes of apexification in immature traumatized necrotic teeth and risk factors for premature tooth loss: A 20-year longitudinal study. <b>Wikström A,</b> Brundin M, Mohmud A, Andersson M, Tsilingaridis G. Dent Traumatol. 2024 Dec;40(6):658-671 <a href="https://doi.org/10.1111/edt.12973" target="_blank">https://doi.org/10.1111/edt.12973</a></p>

This review guidance is a work in progress because the limitations of regenerative endodontics are still being discovered. The endodontic treatments for immature permanent teeth with a necrotic pulp can vary considerably among endodontic practitioners. Whereas, regenerative endodontic treatments are growing in popularity and are creating ever more complex treatment protocols, involving revascularization and/or autologous platelet-rich plasma and scaffolds to elicit host stem cell de novo tissue formation to reestablish the vitality of immature teeth for the purpose of continuing root maturation. Despite much evolving controversy about their potential benefits, risks, prognosis, and contraindications, this review is aimed to discuss how to ensure that regenerative endodontic treatments are successful, by strictly adhering to case selection criteria, and following precise steps to accomplish and monitor the success of the treatment. A review of the endodontic literature was performed, together with practical observations of the problems and outcomes of performing regenerative endodontic treatments. Traditionally, apexification has long been the treatment of choice provided to immature teeth with a necrotic pulp. Regenerative endodontics may be provided as an alternative to apexification, if the tooth and patient meet all the case selection criteria, and if there are no contraindications. Regenerative endodontics has the unique potential advantage of being able to continue the root development in immature permanent teeth, thereby potentially saving the teeth for the lifetime of the patient. Whereas, conventional endodontic root canal treatment, Cvek partial pulpotomy, apexogenesis, and apexification, should always be provided when these treatments are more likely to benefit the patient because they can be more successful than regenerative endodontics.

ABSTRACTPreserving the natural dentition in its normal form and function is one of the major goals of endodontic treatment. Re-establishing the lost vitality and development of root maturation in immature permanent teeth with pulp necrosis/apical periodontitis is quiet challenging clinically. The very basis of regenerative endodontics relies on the concept of tissue engineering using stem cells, biomimetic scaffold, and bioactive growth factors to regenerate the pulp tissue damaged by microbial infection, injury, or developmental defects. In clinical endodontics, this approach is referred to as a “paradigm shift.” Even though repair instead of true regeneration is achieved with current protocols, it is hoped that further research in the area of stem-cell-based tissue engineering will allow for true regeneration and improved treatment outcomes. The aim of this review is to discuss about the various aspects of regenerative endodontics, current clinical protocols, and the future of pulp regeneration techniques.

Autotransplantation and regenerative endodontic treatment are biologically based dental treatment modalities. Autotransplantation may be a more affordable alternative to implants for patients who experience tooth loss at a young age. Regenerative endodontic treatment is also an alternative to routine endodontic treatment as it can allow the regeneration of necrotic or inflamed pulp tissue. The aim of this case is to report a successful 3-year treatment outcome in an immature tooth using a combination of autotransplantation and regenerative endodontic treatment. An 18-year-old female patient with complaints of severe pain and mobility at 37. The patient’s medical history revealed no systemic disease. Clinical and radiographic examination revealed that 37 had undergone root canal treatment 3 years ago. Retreatment of the root canal was initiated, but the symptoms did not improve despite interm treatment. After surgical consultation, it was decided to extract 37. For autotransplantation, 38 was extracted atraumatically and autotransplanted into the socket of 37 and splinted for 2 weeks. Regenerative endodontic treatment was planned due to the radiolucency observed in the periapical area of the tooth at the 6-month follow-up. Regenerative endodontic treatment was performed on the autotransplanted tooth using platelet-rich fibrin obtained from the patient’s own blood. The tooth remained asymptomatic and functional for 3 years. Root development continued and periapical healing was complete at 6 months. The tooth showed a positive response to pulp sensitivity tests at the 1-year follow-up. The combination of autotransplantation and regenerative endodontic treatment can be considered as a long-term treatment option for immature teeth. Keywords: Autotransplantation; Regeneration; Revascularisation; PRF; Vital pulp therapy

Recent considerations in regenerative endodontic treatment approaches

Traditionally, apexification has been used to treat immature permanent teeth that have lost pulp vitality. This technique promotes the formation of an apical barrier to close the open apex so that the filling materials can be confined to the root canal. Because tissue regeneration cannot be achieved with apexification, a new technique called regenerative endodontic treatment was presented recently to treat immature permanent teeth. Regenerative endodontic treatment is a treatment procedure designed to replace damaged pulp tissue with viable tissue which restores the normal function of the pulp-dentin structure. After regenerative endodontic treatment, continued root development and hard tissue deposition on the dentinal wall can occur under ideal circumstances. However, it is difficult to predict the result of regenerative endodontic treatment. Therefore, the purpose of this study was to summarize multiple factors effects on the result of regenerative endodontic treatment in order to achieve more predictable results. In this study, we investigated the features of regenerative endodontic treatment in comparison with those of other pulp treatment procedures and analyzed the factors that have an effect on regenerative endodontic treatment.

BackgroundRegenerative endodontic treatment (RET) is a promising treatment alternative for traumatized immature non-vital teeth. Advanced platelet-rich fibrin (A-PRF) contains significantly more growth factors than Platelet-rich fibrin (PRF) and has not been evaluated as a scaffold in RET. The aim of the present study was to evaluate and compare A-PRF and PRF as scaffolds in the RET concerning periapical healing, and root development of traumatized immature non-vital teeth.Material and MethodsIn the present study, RET was performed on 30 traumatized immature non-vital maxillary incisors in 28 patients aged between 8-27 years. Minimal mechanical debridement and irrigation with 1.5% sodium hypochlorite and 17% ethylenediaminetetraacetic acid was performed. Canals were disinfected using modified triple antibiotic paste consisting of ciprofloxacin, metronidazole and cefaclor. Based on the type of scaffold, teeth were randomly assigned into A-PRF (n=15) and PRF groups (n=15). Periapical healing, apical response and quantitative root dimensions (length and thickness) were analyzed radiographically after 12 months follow-up. ResultsNineteen patients with 21 teeth (A-PRF n=11, PRF n=10) completed the follow-up and 9 patients were excluded. Clinically, patients in both the groups were asymptomatic. The survival rates for A-PRF and PRF were 78.5% and 77.5%, respectively. No statistically significant differences were detected between A-PRF and PRF regarding periapical healing and type of apical response (p& 0.05). The difference in the pre-operative and follow-up root thickness and root length in both A-PRF and PRF groups were statistically significant (p< 0.05). ConclusionsBased on short-term results of 13 months, both A-PRF and PRF can be used as scaffold in regenerative endodontic treatment of traumatized immature non-vital teeth. A-PRF could be recommended in such cases since it yielded more root dentin thickness which is crucial for reinforcing immature teeth. Key words:Regenerative endodontic treatment, dental trauma, Non-vital teeth, immature teeth, platelet-rich fibrin, advanced platelet-rich fibrin.

Histologic and Immunohistochemical Findings of a Human Immature Permanent Tooth with Apical Periodontitis after Regenerative Endodontic Treatment

Regenerative Endodontic Treatment with Orthodontic Treatment in a Tooth with Dens Evaginatus: A Case Report with a 4-year Follow-up

Regenerative Endodontic Treatment in Immature Noninfected Ferret Teeth Using Blood Clot or SynOss Putty as Scaffolds

Regenerative endodontic treatment (RET) has been suggested for the treatment of traumatized necrotic immature teeth. There are only a few reports of using RET to treat a horizontal root fracture. The aim of this paper is to describe successful regenerative retreatment in a tooth with a horizontal root fracture and dens invaginatus.A 9-year-old boy presented with a horizontal root fracture in a central incisor. Pulp necrosis and inflammatory root resorption were observed. The tooth was treated by RET, including calcium hydroxide dressing between visits. After bleeding was allowed into the canal space, a collagen plug was placed as a barrier, and covered by a bioceramic material. At the completion of treatment, the resolution of the radiolucent lesion was evident. During follow-up, the tooth exhibited recurrent pathology at the fracture line. The patient was scheduled for retreatment of the tooth. Repeated RET included additional ultrasonic irrigation and calcium hydroxide dressing. One year after the completion of retreatment, the periradicular lesion resolved with continued maturogenesis of the apical fragment and approximation of the coronal and apical fragments that were attached by a calcified tissue and surrounded by the continuous periodontal ligament.ConclusionThis rare case report of retreatment after failed RET is notable for the repeated use of a regenerative procedure subsequent to a recurrent traumatic injury to the tooth. The repeated regenerative endodontic procedure (REP) resulted in the resolution of the periapical lesion and the reunion of the apical and coronal fragments.Clinical significanceFailure of an already successful RET due to a recurrent traumatic injury may be successfully treated by repeating the RET, particularly when the alternative treatment option is extraction.How to cite this articleMarjy Z, Slutzky-Goldberg I. Retreatment of a Failed Regenerative Endodontic Treatment in an Immature Tooth with a Horizontal Root Fracture: A Case Report. Int J Clin Pediatr Dent 2024;17(10):1168-1171.

This study introduces the alveolar-derived autologous blood (ADAB) clot, obtained by maxillary alveolar bone puncture, as a novel scaffold for regenerative endodontic treatment (RET). The purpose of this study is to verify the feasibility of using ADAB clots in RET by evaluating their cellular content, postoperative pain intensity, and clinical outcomes in the management of immature permanent teeth with pulp necrosis. Blood routine examinations were performed to analyze the cell content of peripheral venous blood (PVB) and ADAB. Postoperative pain intensity scores were recorded using the Numerical Rating Scale (NRS) at four time points: upon complete recovery from anesthesia, and at 12, 24, and 48h postoperatively. Five immature premolars with pulp necrosis were treated by RET with ADAB clots. Radiographic root area (RRA) was analyzed using ImageJ software on oral radiographs obtained immediately after treatment and at the final follow-up (6-18months). The percentage difference in cell types between two groups (n = 8 per group) were not significant, except for blood platelets (PLT). The PLT count in the ADAB group (133.38 ± 119.62) was approximately half that of the PVB group (268.88 ± 52.82). Postoperative pain (n = 9) was predominantly mild upon anesthesia recovery and at 12h postoperatively, while the majority of participants reported no pain at 24 and 48h postoperatively. The mean RRA (0.50 ± 0.11) in the final recall radiographs was significantly larger than that in the immediate postoperative radiographs (0.35 ± 0.16) (P = 0.046 < 0.05). Based on this study, the ADAB clot shows potential as an alternative scaffold for RET. Because it can be obtained via maxillary terminal alveolar bone paracentesis with mild postoperative pain intensity and successfully promotes root regrowth. However, the coagulation time of ADAB may be longer than that of PVB, and root regrowth outcomes appear to depend on the developmental stage of the tooth. Hence, further clinical trials are necessary to comprehensively evaluate the clinical efficacy of the ADAB clot. Compared to autologous platelet concentrates (APCs) derived from PVB, ADAB clots offer advantages in RET, especially in cases where periapical bleeding is insufficient to fill the root canals. ADAB clots can be prepared independently by dentists without the need for a qualified nurse for blood collection or specialized centrifugation equipment. Furthermore, the volume of blood required to fabricate an ADAB clot is less than that needed for APCs from PVB.

Regenerative endodontic treatment is an alternative approach for immature necrotic permanent teeth. This method, is based on disinfection of the root canal system and periapical region without damaging the existing cells. The aim is to assist in the formation of new tissue within the canal after the stem cells are transported to the root canal and to induce further root development. Studies on Stem cells, signalling molecules and scaffold which is triad of regenerative endodontic treatments concept are increasing nowadays thanks to intensive progress of regenerative medicine and tissue engineering. This review outlines the clinical protocols currently used and studies in regenerative endodontic procedures. Keywords: Regenerative endodontic treatment, stem cells, scaffold, calcium hydroxide, immature teeth and pulp necrosis.

Objective: To apply regenerative endodontic treatment to immature permanent molar teeth devitalised due to dental caries and to follow the clinical and radiographic outcomes. Cases: Four patients presented to our university with complaints of pain. Radiological evaluations revealed profound dentinal caries, apical lesions, and open root tips. Clinical examinations yielded negative results on the electric pulp test (EPT) for all four teeth. Given the presence of immature necrotic teeth, the treatment for these cases was planned as regenerative endodontic treatment. This treatment was administered under local anaesthesia, following the protocol recommended by the American Endodontic Association. Results: Over a follow-up period of 10 to 15 months, certain patients exhibited a reduction in periapical lesions and completion of root formation. However, root development persisted in other patients. Conclusion: Follow-up and observations indicate that regenerative endodontic treatment is an effective alternative for the management of immature permanent molar teeth.