Regenerative Therapy for the Permanent Immature Teeth: A Long Term Study. An Original Research

ABSTRACT

Introduction:

Endodontics faces several clinical difficulties while treating young necrotic permanent teeth. The use of regenerative endodontic procedures (REPs) enables apical closure, improved canal wall thickness, and root growth. The objective of this study was to assess the effects of these regenerative procedures on immature necrotic permanent teeth.

Methods:

This prospective clinical study was conducted at the tertiary care hospital for the study period of 2 years. This study includes 30 necrotic permanent immature teeth that were studied in 30 subjects of both genders. A standard REP protocol was used to treat every tooth. A follow-up visit was scheduled for each patient at timely intervals. Various study parameters as well as the demographics were assessed at each visit. To examine various parameters, a calibrated endodontist also performed a radiographic evaluation.

Results:

Our findings point to excellent rates of survival, clinical success, and apical pathological resolution for 29 teeth. After 2 years, there were significant variations in the root thickness area and the average root length. The apical diameter significantly decreased during the research period, with 30.8% of the instances exhibiting full apical closure. Apical diameter, root length, and thickness changed more frequently in teeth with the level of the immaturity of the root, although the variations were not significant.

Conclusions:

REP treatment for teeth preceded symptom relief. Increased root thickness, root length, and apical closure were seen at 30 months, even if the clinically meaningful change was not attained in all patients.

INTRODUCTION

Immature necrotic teeth can be treated with regenerative endodontic therapy or revascularization. The large canals and open apices make it challenging for the doctor to perform various steps that are intended in “Root Canal Therapy.”[1] Alternative approaches include the application of various caustic materials like calcium hydroxide or recent materials like the “Mineral Trioxide Aggregate-MTA”. Though it is established that they form barriers it is not well known if they similarly allow for root lengthening to the physiological development. There is also the disadvantage of thin root walls and hence there is a chance of fractures for these teeth treated with the above chemicals. Since the roots are just closed with these substances there is a disproportion between the crown-to-root- C: R ratios.[1,2]

A new method of the treatment of immature roots was introduced “Regenerative endodontic procedures (REPs).” This may according to studies, may aid in the physiological root development as much as possible and hence will help in maintaining the C: R ratios.[3-6] For sustained root development, this method depends on the survival of stem cells from the “Hertwig epithelial root sheath” and “Stem Cells from the Apical Papilla (SCAPs)”, as well as the release of various growth factors from the dentinal walls.[7] The objectives of REP are to get rid of the patient’s symptoms, lengthen and thicken the roots, and get a favorable reaction to vitality testing.[8] However, there are no long-term studies on the application of these newer regenerative techniques to the immature roots.[9] Therefore, The objective of this study was to assess the effects of these regenerative procedures on immature necrotic permanent teeth.

MATERIAL AND METHODS

A prospective clinical observational study was conducted at the tertiary care hospital. The study was conducted for 2 years. The ethics clearance was taken. The patient and the guardian’s written consent were taken for the study. The subjects considered for the study were both genders. They were healthy with no other medical conditions. The radiographs were taken for the enrolled subjects and diagnostic tests were performed to select the suitability of the test. Only those subjects who had immature apex of permanent teeth were considered for this clinical study. The subject who had immune reactions to the materials that were used in the root canal therapy was excluded from the study.

For the selected studies the peri-apical pathologies were established in the IOPA. Along with that the length and the apical opening width as well as the thickness of the dentinal walls were scaled. The root’s stage of development was classified as 1, 2, 3, or 4, according to how much of the root had formed at each stage.[10] Stage 5 was not considered for the study.

Performing the REPs

The procedure was performed by specialists who had previous training in the REPs. The designated teeth were isolated with a barrier after being sedated with 2% lidocaine and 1:100,000 epinephrine. Without using any instruments, access was established and 5.25% sodium hypochlorite was used to irrigate the canal. Working length established with a file and IOPA taken. A triple antibiotic paste was then introduced with a Lentulo spiral to about 1 mm short of apex after it was dried. The paste’s ingredients were propylene glycol and macrogol as a basis, metronidazole, ciprofloxacin, and cefaclor powder at various proportions. Minocycline was substituted with cefaclor as recommended by several authors.[6,11] After that, teeth were sealed with GIC and Cavit of companies (3M ESPE, Seefeld, Germany) and (GC Fuji IX; GP Corp, Tokyo, Japan) respectively. 2 to 6 weeks later, patients went back. It was confirmed that the infection, edema, and pain had subsided. The channel was reopened, a rubber dam was put in place, and 5.25% sodium hypochlorite was irrigated through it. Mepivacaine 3% without a vasoconstrictor was utilized. With paper points, the canal was then dried. By excessively filing 1–2 mm into the peri-apical tissues, to aid in the blood clot establishment. Later the MTA was placed on the base of the collagen that was placed away from the CEJ based on the apical width. Cavit was placed on it. The temporary restoration was restored with GIC after one week.

Follow-up

The visits were piloted every 2 months for 2 years. The weeks considered in the study were 1,6,16,24 months. The clinical and radiographs were collected at these times.

Parameters studied

Plug-ins are available from the Swiss Federal Institute of Technology, Lausanne, to adjust for various angulations and slight distortions.[12] The task of assessing preoperative and postoperative study radiographs was assigned to one endodontist (M.C.). 30 selected radiographs from REP representative instances were used for the examiner’s (M.C.) calibration. Before the start of the evaluation, there had to be a 95% agreement between the examiners. The following factors were examined in all radiographs: root length, thickness, and apical closure. Additionally, it was necessary to check for the absence of bone healing and/or radiographic pathoses (radiolucency or resorption). Although it was seen, discoloration was not considered when determining success or failure. A tooth that is retained after REP is regarded to have survived, whereas a tooth that is extracted is deemed to have failed.

Analytical statistics

All variables underwent descriptive analysis that included mean and standard deviation. The clinical and demographic data of the patients were represented as frequencies and percentages. These values were analyzed using the Chi-square test. For the descriptive analysis, the central tendency and dispersion indices were displayed using the relevant charts and tables. Using SPSS 23, the P < 0.05 was taken as significant.

RESULTS

Characteristics of subjects

In this investigation, 30 immature, necrotic, permanent teeth were used. The average age of the individuals in this population was 9 years, and approximately half of them—54.5%—were male. Central incisors made up the majority of the treated teeth (75%), and traumatic damage was the leading cause of tooth necrosis (78%). Radiographic periapical radiolucency was evident in the majority of cases (75%), along with abscess or cellulitis symptoms in 57.1% of cases. 24 months on average passed between follow-ups.

CLINICAL RESULTS

The survival percentage of 97%; one tooth that required additional treatment was excised for economic reasons. The clinical success rate in this trial was 93%; nevertheless, one tooth needed additional care (MTA apexification) due to reoccurring complaints. Discoloration, the only unfavorable event identified, was seen in more than half of the instances (58%). All instances of discoloration included teeth that had previously sustained damage.

RESULTS OF RADIOGRAPHY

The radiographic apical closure was complete in about 31% of the cases. There was a significant reduction in apical diameter (P <.0001). The average apical diameter reduction at 24 months was 35%. According to the standard that a clinical radiographic change is defined as a 20% difference 83% of the cases met this standard. The root length (93%), and root thickness (82%). MTA thickness and density had no discernible impact on radiographic results. Significant root length variations were seen at the end of the study period (P <.0001) and radiographic root area (P < 0.05). The root parameter changed more frequently in teeth with the level of the immaturity of the root, although the variations were not significant in Tables 1 and 2.

Table 1.

Observations made from the comparison of the radiographs

Parameters	%
Apical closure
No closure	16
Partial closure	54
Complete closure	31
Healed periapical pathoses
Completed	100
Root length increase
No	9
Yes	93
Increase in root thickness
No	19
Yes	82

Table 2.

Change in the Radiographic levels for the different root stages

Root stage	Change in radiographic root area	Change in length	Change in apical diameter
1	15	9	36
2	17	14	41
3	10	7	37
4	7	5	20

DISCUSSIONS

The application of Regenerative therapy has been deemed an effective way in the treatment of immature permanent teeth that were necrotic.[10-20] However the time that was planned for the follow-up was for a few weeks or months. Hence this study was planned for at least 2 years. A period of two years will be optimal for observation of the changes that occur in the apex that can be noted on the radiographs.

The findings of this study demonstrate that 93% of the cases had a clinically effective clearance of periapical radiolucencies. This outcome is consistent with research reporting clinical success rates of 78%–100% however a few studies have reported greater failure rates.[20-22]

The discoloration was seen in over half of the teeth in the subjects. This may be attributed to the antibiotic paste that was placed in the root canal. Discoloration of the teeth with the antibiotic paste is commonly observed in other studies also.[23,24] According to previous studies, MTA use may potentially be a contributing factor to discoloration.[11,25] In fact, it has been demonstrated that mixing sodium hypochlorite or blood products with MTA, particularly bismuth oxide, results in the formation of a black precipitate.[25,26] White MTA also exhibits a dark discoloration after curing.[27] Even though MTA was placed under the CEJ with care, discoloration nevertheless happened occasionally. It was interestingly discovered that all the discolored teeth in this study had developed necrosis due to severe injury. Trauma may also have caused discoloration because of pulp bleeding and the creation of iron sulfide following red blood cell hemolysis.[28]

Total apical closure was achieved in 31% of the subjects compared to one other study’s finding that apical closure occurred in 19.4% of cases after 18 months.[29] In contrast, a different study revealed that after a year, 55% of apical closure had occurred.[15] The greater age of the individuals included in the latter trial may explain this disparity. The stage of root development may have fully matured in older patients.

In 28 patients the apical closure was fully achieved in 2 years; when the threshold of 20% was considered as a meaningful clinical change. This study’s average radiographic root area change was 11.6%, which is lower than the earlier studies in the thickness range of 11–27%.[14,15,19] In the aforementioned research, when the overall increase in root width was recorded as a straight line, there is a noticeably different methodology for measuring root canal thickness. Because the radiographic root area can be viewed as a more accurate assessment of the entire root, it was selected in this study to assess the growth in root wall thickness. The etiology can also contribute to differences; in this study, 21.4% of the teeth had a history of intrusion and avulsion. These acute lesions may harm not only the tooth’s periodontal structure but also nearby stem cells due to the subsequent effect on the surrounding tissue. Although a statistically significant change in root width based on RRA was discovered, this variation is typically smaller and cannot be regarded as a shift with clinical significance.

The average rate of ongoing root lengthening across all the patients examined in this study was 9%. This outcome is consistent with research indicating a 5%–15% increase in root length.[14,19] The clinical findings were not as evident as the radiographic root lengths at the end of 2 years. The change in the length was inversely proportional to the maturity of the tooth. Stages 1 and 2 showed greater improvement than Stages 3 and 4. Stem cells, that can move to the designated areas for dentin deposition and develop into odontoblasts, have been hypothesized to be associated with continuing root formation.[30-32] It may be possible to administer more SCAPs during the early phases of tooth growth when teeth have broader apexes, which could help to explain our findings.

At the subsequent exams, none of the teeth in this study showed a positive response to the cold test. Histologic investigations show that in teeth treated with REP, a real pulp-dentin complex has not yet been created because the root is typically filled with tissue that resembles cementum, bone, and fibrous connective tissue.[33] Furthermore, there is little chance that a tooth will react to sensitivity tests because any produced essential tissues would be apical to the pulp chamber. Also, the internal walls of the tooth are developing an osteodentin layer,[34] which makes it challenging for a tooth to respond positively to vitality tests.

The findings of this study should be interpreted considering its limitations. First, it was difficult to maintain the same radiographic angulation because this investigation was carried out for two years on adolescents and children with mixed dentition. The radiographic images’ placements were standardized using TurboReg software to offset this effect. However, several radiographs’ angulations could not be fixed, therefore they had to be eliminated from part of the analyses. Second, despite following a uniform protocol, the procedure was carried out by 3 distinct operators, which can lead to inconsistent findings. However, a recent analysis of the REP literature reveals that particular methodologies had little impact on the technique’s effectiveness.[35] Despite these drawbacks, the current study sheds further light on the 30-month success of REPs in the long run.

CONCLUSION

In summary, REPs demonstrated excellent rates of success. Side-effect discovered was discoloration, which only happened in teeth that had been damaged. The radiographic finding with the highest degree of consistency was a shift in apical diameter. Root length and RRA both increased, while the latter presented less development following REP. further research is essential to corroborate this study’s findings.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient (s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.