| Reference | Study type | Population | Intervention and comparison | Outcomes | Risk of bias |
|---|---|---|---|---|---|
| «Torabinejad M, Nosrat A, Verma P ym. Regenerative ...»1 | SR/MA | Comparative, noncomparative, prospective, and retrospective clinical studies on immature teeth with pulp necrosis treated with RET 750 → 144 studies were subjected to qualitative synthesis → 10 randomized clinical trials in subgroup analyses1966 through 2016, USA | To compare the outcome between MTA apical plug (MAP) and regenerative endodontic treatment (RET) | Average follow-up time in each study was calculated Survival was defined as a retained tooth in the oral cavity at follow-up. Success was defined as a lack of clinical symptoms (ie, pain on percussion /palpation/function or sinus tract) and complete radiographic healing of the periapical lesion. Reduction in the size of the periapical lesion was classified as ‘‘uncertain''. The rate of root development was extracted from RET studies. Root development was defined as increased root length, increased root thickness, or reduced apical diameter. |
MAP 12% high ROB, 29% low and rest moderate RET 25% high and low ROB Majority of studies case reports, case series |
| «Ong TK, Lim GS, Singh M ym. Quantitative Assessmen...»2 | SR/MA | Studies, in which any procedure that attempted to revascularize or regenerate a necrotic immature permanent human tooth with the intention to induce root development was included as RET USA 1990–2019 of 3088 studies 11 were included |
Treatment protocol: NaOCl 0.5–5.25%, antibiotic paste, in some studies EDTA, blood clot and MTA j RCT-studies compared blood clot to protein rich plasma or protein-rich fibrin | Survival: tooth retained after the treatment at follow-up. Healing: absence of clinical symptoms with resolution of periapical radiolucency. Root lengthening was defined as the increment of the root length. Root thickening was defined as the increment of root thickness. Apical narrowing/closure was defined as narrowing of the apical diameter of the root. |
ROB high in 2 randomized controlled trials, and low in 1 RCT. High level of bias was found in all uncontrolled prospective trials. Both cohort studies were considered of high quality. i2=0, heterogeneity low |
| «Duggal M, Tong HJ, Al-Ansary M ym. Interventions f...»3 | SR/MA | Systematic review covered literature on all techniques for inducing an apical barrier in traumatized non-vital immature permanent anterior teeth, UK 1966 → of 200 studies, included studies were for Apexification → 6 MTA plug → 8 RET → 8 |
Studies on techniques such as apexification, apical plug formation using MTA, and RET with at least 12 months follow-up were included and compared with conventional root canal obturation or no treatment | The primary outcome measure was the proportion of teeth that were symptom-free for
at least 12 months after treatment. The secondary outcome measure was the total duration of treatment time to achieving an apical barrier. |
Apexification: 50% of the studies met most of the quality assessment criteria. MTA plug (MAP) use: current available evidence does not meet the Cochrane quality criteria RET: so far the level of evidence is low |
| «Peng C, Yang Y, Zhao Y ym. Long-term treatment out...»4 | Cohort | Retrospective (patient records) clinical study on evaluating long-term outcomes of revascularisation in non-vital immature permanent
teeth. China 2009–2012 number of patients 60 |
RET outcome with at least 12 month outcome using MTA or glass ionomer cement (GIC) as canal-sealing materials | Treatment outcomes were assessed as tooth survival and success. Changes in root dimensions between the preoperative and final post-operative images were evaluated by measuring and calculating the changes in root length and dentine wall thickness. |
SR=systematic review; MA=meta-analysis; ROB=risk of bias; RCT=randomized controlled trial
| Reference | Comments |
|---|---|
| «Torabinejad M, Nosrat A, Verma P ym. Regenerative ...»1 | Any organized attempt to revitalize a necrotic immature tooth to induce root development
was considered as RET (all methods of disinfection, all types of scaffold/all types
of sealing materials). If the clinician filled the apical part or the entire root
canal space with MTA without the intention of revitalizing the tooth, the treatment
was considered as MAP. Studies using materials other than MTA were excluded. Trauma was the most common etiology for pulp necrosis in both groups (60% and 62% of the studies in the MAP and RET groups, respectively). Anterior teeth were the most common tooth type treated in both groups (78%). Sodium hypochlorite (0.5%–6%) was the only irrigant or the main irrigant in 52 (85%) and 81 (95%) studies in the MAP and RET groups, respectively. Calcium hydroxide (alone or combined with other antibacterial medicaments) was the most common type of intracanal medicament in the MAP group (82% of studies). The most common intracanal medicament used in the RET group was different combinations of antibiotics in 64 (75%) studies followed by calcium hydroxide in 14 (17%) studies. One study (1%) used formocresol. The treatment was performed in 1 visit in 6 (7%) studies. In MAP studies application of intracanal medication ranged from months (3%) to weeks (41%) or days (31%). Treatment was completed in one visit in 14% of studies. In the RET group, application of intracanal medication ranged from months (7%) to weeks (73%) or days (8%). In 7% of studies, treatment was completed in 1 session. In the RET group, the most common scaffold was a blood clot (65 studies), and the most common barrier over the scaffold was MTA (71 studies). EDTA was used in 17 (20%) studies. |
| «Ong TK, Lim GS, Singh M ym. Quantitative Assessmen...»2 | The criteria for excluding studies were: Non-human studies, abstract and title do not meet the inclusion criteria, review articles, descriptive case report or case series, non-English studies, study included primary teeth or mature permanent teeth, full article not found. |
| «Duggal M, Tong HJ, Al-Ansary M ym. Interventions f...»3 | Studies using various techniques in RET were considered as RET here (BC Blood Clot,
PRP platelet rich plasma, PRF platelet rich fibrin, TAB tri antibiotic paste (ciprofloxacin,
minocycline, metronidazole), TAPC tri antibiotic paste (Ciprofloxacin, Minocycline,
cephaclor), TABD tri antibiotic paste (ciprofloxacin, doxycycline, metronidazole),
Ca(OH)2 calcium hydroxide, FC ferric sulphate, MTA mineral trioxide aggregate, NSRCT
conventional root canal treatment with gutta percha, GP gutta percha only, FGF blood
clot and injectable hydrogel scaffold impregnated with basic fibroblast growth factor,
UK unknown scaffold. Exclusion criteria comprised non-relevant studies, case reports, in vitro, animal studies, and retrospective studies. Three studies on MTA plugging as well as RET were excluded from here, because the age of the participants varied from 18–64 y or did not indicate immaturity of the teeth involved. Drop-out rate during the monitoring period may have caused some bias on the outcome |
| «Peng C, Yang Y, Zhao Y ym. Long-term treatment out...»4 | Of the teeth in the study population 85% were premolars, the rest incisors. Cause for RCT was anatomic (dens in dente, invagination etc.) in 82%, caries in 5% and trauma in 13% and diagnoses were fairly evenly distributed between SAP, symptomatic apical periodontitis; acute apical abscess (AAA); chronic apical abscess (CAA) |
I= intervention; C=comparison; CI=confidence interval
| Reference | Number of studies and number of patients (I/C) | Age range (y) |
Follow-up time (months) | Success rate, periapical healing (%) |
|---|---|---|---|---|
| «Torabinejad M, Nosrat A, Verma P ym. Regenerative ...»1 RETSR/MA |
144 studies/61 MAP and 85 RET, for meta-analysis 10 studies. Number of teeth: RET n=455 MAP n=543 |
MAP 6–35 RET 6–39 |
MAP2–120 RET 6–72 |
Success rate: MAP 94.6% (95% CI, 90.2–99.1%) RET 91.3% (95% CI, 84.5–98.2%) |
| «Torabinejad M, Nosrat A, Verma P ym. Regenerative ...»1 | Studies on relative effect of MAP (6 studies) and RET (4 studies) Number of teeth: RET n=87 MAP n=92 |
Relative effect of MAP 0.946 (0.902,0.991) RET 0.913 (0.845, 0.982) |
||
| «Duggal M, Tong HJ, Al-Ansary M ym. Interventions f...»3 RETSR/MA |
5 (/8) number of patients: RET n=96 MTA n=43 CaOH2 n=33 |
7–17 y | 1–27, usually at least 12 m | Success rate of periapical healing RET: 92% MTA: 68% (MAP) CaOH2: 79% (Apexification) |
| «Peng C, Yang Y, Zhao Y ym. Long-term treatment out...»4 RET Retrospective Cohort study |
Retrospective study n=60 MTA n=28 GIC n=32 |
MTA 10.7 y +/- 2.2 y GIC 10.8 y +/- 1.6 y |
MTA 34.3 +/- 10.0 GIC 38.0 +/- 14.6 |
Success rate of RET using MTA 93% GIC 59% |
| Level of evidence: high/moderate/low/very low Assess the risk of bias and delete irrelevant sources of bias: Level of evidence is good for the success of RET, but similar with MAP |
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| Reference | Number of studiesand number of patients (I/C) | Age range (y) |
Follow-up time (months) | Survival rate (%, (95% CI)) |
|---|---|---|---|---|
| «Torabinejad M, Nosrat A, Verma P ym. Regenerative ...»1 RET SR/MA |
144 studies/85 RET and 61 MAP RET n= 455 (teeth) MAP n = 543 (teeth) |
RET 6–39 MAP 6–35 |
RET 6–72 MAP2–120 |
RET 98% (94.8–100%),MAP 97% (93.7–100%) |
| «Ong TK, Lim GS, Singh M ym. Quantitative Assessmen...»2 RET SR/MA |
11 studies / n=289 (teeth) | 12–93 | 97% (94.3–98.8 %) | |
| «Peng C, Yang Y, Zhao Y ym. Long-term treatment out...»4 RET |
Retrospective study n=60 (teeth) MTA n=28 GIC n=32 |
MTA 10.7 y +/- 2.2 y GIC 10.8 y +/- 1.6 y |
MTA 34.3 +/- 10.0 GIC 38.0 +/- 14.6 |
MTA 96% GIC 100% |
| Level of evidence: high/moderate/low/very low Assess the risk of bias and delete irrelevant sources of bias: Level of evidence is good for survival |
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| Reference | Number of studiesand number of patients (I/C) | Age range (y) |
Follow-up time (months) | Apical closure and root development (% (95% CI)) |
|---|---|---|---|---|
| «Torabinejad M, Nosrat A, Verma P ym. Regenerative ...»1 RET |
144/85 RET RET n=455 teeth |
RET 6–39 |
RET 6 to 72 | RET: The pooled rate for root development to some extent in 79% (67–91%) of the treated teeth |
| «Ong TK, Lim GS, Singh M ym. Quantitative Assessmen...»2 RET |
SR/MA 11 studies Number of teeth: tooth lengthening n=289 root thickenining n=258 Apical Narrowing/Closure n=190 Apical Narrowing/Closure >20% n=73 Radiographic Root Area (RRA) n=68 |
12–93 | Root lengthening 77% (66–85) Root lengthening>20% 16% (6–38) Root thickening 81% (72–87) Root thickening>20% 40% (22–61) Apical closure /Narrowing >20% 79% (66–88) Apical closure/narrowing 91% (75%–97%) |
|
| «Duggal M, Tong HJ, Al-Ansary M ym. Interventions f...»3 RET |
5 (/8) number of patients: RET n=96 (teeth) MTA n=43 CaOH2 n=33 |
7–17 y | 1–27, usually at least 12 m | Root lengthening RET: 19% MTA: 10% CaOH2: 14% Root thickening: RET: 30% MTA: 0% CaOH2: 24% |
| Periapical healing RET: 92% MTA: 68% CaOH2: 79% Apical closure RET: 71% CaOH2: 55% |
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| «Peng C, Yang Y, Zhao Y ym. Long-term treatment out...»4 RET |
Retrospective study n=60 (teeth) MTA n=28 GIC n=32 |
MTA 10.7 y +/- 2.2 y GIC 10.8 y +/- 1.6 y |
MTA 34.3 +/- 10.0 GIC 38.0 +/- 14.6 |
Root lengthening: MTA 11% GIC 11% Root thickening MTA 30.7% GIC 26.3% |
| Level of evidence: high/moderate/low/very low The level of evidence seems good for apical narrowing/closure as well as for apical closure, moderate/low for root thickening and low for root lengthening |
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