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Background:
Review

Healing Ability of Endodontic Filling Materials in Retrograde Treatment: A Systematic Review of Clinical Studies

by
Tarek Ashi
1,
Rim Bourgi
1,2,3,
Carlos Enrique Cuevas-Suárez
4,*,
Louis Hardan
2,
Carmen Nahat
5,
Zaher Altaqi
6,
Naji Kharouf
1,7,* and
Youssef Haikel
1,7,8
1
Department of Biomaterials and Bioengineering, INSERM UMR_S 1121, University of Strasbourg, 67000 Strasbourg, France
2
Department of Restorative and Esthetic Dentistry, Faculty of Dental Medicine, Saint-Joseph University of Beirut, Beirut 1107 2180, Lebanon
3
Department of Restorative Sciences, Faculty of Dentistry, Beirut Arab University, Beirut 115020, Lebanon
4
Dental Materials Laboratory, Academic Area of Dentistry, Autonomous University of Hidalgo State, San Agustín Tlaxiaca 42160, Mexico
5
Faculty of Dentistry, International University of Catalonia (UIC Barcelona), Sant Cugat del Vallès, 08195 Barcelona, Spain
6
Private Practice, Olaya Street, Riyadh 12213, Saudi Arabia
7
Department of Endodontics and Conservative Dentistry, Faculty of Dental Medicine, University of Strasbourg, 67000 Strasbourg, France
8
Pôle de Médecine et Chirurgie Bucco-Dentaire, Hôpital Civil, Hôpitaux Universitaire de Strasbourg, 67000 Strasbourg, France
*
Authors to whom correspondence should be addressed.
Appl. Sci. 2025, 15(12), 6461; https://doi.org/10.3390/app15126461 (registering DOI)
Submission received: 21 February 2025 / Revised: 3 June 2025 / Accepted: 4 June 2025 / Published: 8 June 2025
(This article belongs to the Special Issue Dental Materials: Latest Advances and Prospects, Third Edition)
Browse Figure
Versions Notes

Abstract

:
The fundamental goal of endodontic surgery is to remove the infection cause and create an ideal environment for periapical tissue and bone recovery. This systematic review aims to present evidence-based findings regarding the healing ability of endodontic materials in retrograde treatment. The study evaluates the advantages and drawbacks of commonly utilized materials, empowering clinicians with valuable insights for preoperative planning in endodontic surgery. A comprehensive search was conducted across multiple databases, including MEDLINE, Scielo, Web of Science, Scopus, Embase, and Google Scholar, using the PIOT framework. A total of 3124 papers were identified, of which 2534 remained after removing duplicates. Following a stringent selection process, 35 clinical studies were included for qualitative assessment. The risk of bias was assessed using the Risk of Bias in Non-randomized Studies—of Interventions (ROBINS-I) tool for non-randomized trials, the Newcastle–Ottawa Scale for cohort studies, and the Joanna Briggs Institute (JBI) critical appraisal checklist for cross-sectional studies. Due to high heterogeneity in study designs and outcomes, a meta-analysis could not be performed. The review identified Super Ethoxybenzoic Acid (Super EBA), Mineral Trioxide Aggregate (MTA), and Intermediate Restorative Material (IRM®), Retroplast, Endosequence®, and gutta-percha as the primary retrograde root filling materials. Follow-up periods ranged from 6 months to 17.5 years. Although the materials showed varying degrees of success, the overall findings highlighted that no single material demonstrated universally superior healing ability. The review also emphasized the need for standardization in future clinical trials to facilitate better comparisons. The selection of retrograde filling materials plays a pivotal role in the success of endodontic surgery. New bioceramic materials like MTA and Biodentine offer improved sealing, biocompatibility, and tissue regeneration compared to traditional materials, leading to better clinical outcomes.

1. Introduction

A growing number of patients prefer tooth preservation, leading to increased demand for surgical endodontic treatments. Endodontic surgery is indicated for teeth with persistent periapical lesions of endodontic origin when nonsurgical treatments have failed or are not feasible. The primary goal is to eliminate infection and create an environment conducive to periapical tissue and bone healing [1,2]. During periradicular surgery, the root-end is resected, exposing an apical dentin surface coated in cementum, which is sealed with a retrograde filling material to prevent microleakage while ensuring biocompatibility and material stability in the apical tissues [3].
Success in endodontic surgery depends on case selection, instrumentation techniques, and importantly, the choice of obturation material [4]. The ideal root-end filling material should be biocompatible, promote tissue regeneration without inflammation, be stable dimensionally, be easy to handle, be minimally soluble in tissue fluids, bond to dental tissue, be radiopaque, be non-absorbable, and not stain surrounding tissues [5].
Various materials have been employed, including amalgam, gutta-percha, zinc oxide-eugenol cements, glass-ionomer cements, composite resins, and silicates [6]. While these materials support tissue healing and bone regeneration, none consistently induce cementum formation or full periodontal ligament repair.
Mineral trioxide aggregate (MTA), a calcium silicate-based material derived from modified Portland cement, has become a preferred option due to its high biocompatibility and sealing ability [7]. Although success rates between MTA and traditional root-end filling materials like Super Ethoxybenzoic Acid (Super EBA) or Intermediate Restorative Material (IRM) show no consistent statistical differences, MTA offers distinct advantages in promoting complete regenerative healing [8]. Moreover, MTA’s sealing properties remain effective even with moisture exposure during treatment.
Nonetheless, MTA has limitations such as difficult handling and long setting time, leading clinicians to consider alternatives like IRM or Super EBA. To overcome these issues, newer calcium silicate-based materials have been developed, with Biodentine (Septodont, Saint Maur des Fossés, France) emerging as a promising alternative. Biodentine features a shorter setting time and favorable physical and biological properties, making it suitable for dentin restoration and pulp capping procedures [9].
A successful outcome in endodontic surgery relies heavily on the quality of apical root canal filling. However, the quest for the perfect retrograde filling material remains ongoing. Consequently, this study aims to present evidence-based findings and evaluate the advantages and drawbacks of commonly utilized materials. The objective is to empower clinicians with valuable insights during the preoperative planning phase of endodontic surgery.

2. Materials and Methods

2.1. Protocol and Registration

This systematic review was registered on PROSPERO [ID: 1048854]. The review followed the guidelines outlined by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) [10].

2.2. Information Sources and Search Strategy

A search strategy (Table 1) was first created for the MEDLINE database using specific keywords for each element of the PIOT framework: population (patients with endodontically treated teeth that had periapical pathosis), intervention (retrograde treatment), outcome (success or failure of the retrograde treatment), and type of study (clinical trials). A control was not used, since there is no gold standard for this treatment. This search strategy was later adapted for other databases, including Scielo, Web of Science, Scopus, and Embase. The first 100 search results from Google Scholar were also reviewed. The database searches were conducted on 18 May 2025.

2.3. Selection Process and Data Collection

After completing the search strategy, an online platform (Rayyan, Qatar Computing Research Institute, HBKU, Doha, Qatar) was employed to organize the retrieved studies and eliminate duplicates. The software also helped in the screening of titles and abstracts. This step was undertaken by two independent reviewers who ensured that the selected articles met the inclusion criteria: clinical trials that reported the healing ability of endodontic materials in retrograde treatment were included, irrespective of the materials used. Additionally, only articles with follow-up data and publications written in English, Spanish, or Portuguese were considered. In vitro studies, case reports, case series, pilot studies, and reviews were excluded.
Each article that met the criteria was assigned a unique identification code derived from the first author’s last name and the publication year. The two reviewers worked together to extract and classify the data, including type of study, number of patients included, number of teeth treated, retrograde root filling materials used, follow-up, and main results. In cases of disagreement between reviewers, a third expert was consulted to assist in resolving discrepancies.

2.4. Quality Assessment

Risk of bias was assessed by two independent reviewers for all the included clinical trials, and discrepancies were resolved by discussion and in consultation with a third reviewer. All included studies were assessed, using specific tools for each experimental design: Risk of Bias 2 (RoB-2) for randomized clinical trials [11], Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) for non-randomized clinical trials [12], Newcastle–Ottawa for cohort studies [13], and Joanna Briggs Institute (JBI) for cross-sectional studies.

3. Results

A comprehensive search across all databases yielded 3124 papers. After eliminating duplicates, the titles and abstracts of 2534 documents remained. From this, 47 studies were selected for an in-depth full-text review. Of these, 12 were excluded for the following reasons: 2 were in vitro studies [14,15], 5 did not evaluate the overall success [16,17,18,19,20], 2 did not perform any retrograde procedure [21,22], 2 did not specify the retrograde material [23,24], and 1 was in Chinese [25]. Ultimately, 35 articles were included in the qualitative assessment. Due to a high heterogenicity in the study design, materials, and follow-ups, a meta-analysis could not be performed. The selection process is depicted in Figure 1, in accordance with PRISMA guidelines.
Table 2 outlines the key characteristics of the studies included in the qualitative analysis. The retrograde root filling materials used identified in this systematic review were Super EBA, MTA, IRM®, Retroplast, Endosequence®, and gutta-percha. The follow-up of the studies ranged from 6 months to 17.5 years, and the study design included non-randomized clinical trials, randomized clinical trials, and descriptive studies.
Table 3 shows the results from the risk of bias analysis for randomized clinical trials. Most of the studies were classified as having low risk of bias in almost all the domains. For non-randomized clinical trials, the results from the risk of bias analysis are shown in Table 4. Almost all the studies were classified as having a low risk of bias in all domains. The risk of bias analysis for the cohort studies is depicted in Table 5, and the quality score was ranked between 4 and 6. Finally, the analysis of the risk of bias for the cross-sectional studies is showed in Table 6. The average quality score ranged between 4 and 6. The criteria that most failed were those related to the identification of confounding factors.

4. Discussion

This systematic review aimed to assess evidence-based findings and evaluate the advantages and disadvantages of commonly used filling materials in endodontic retrograde surgery. Clinical studies demonstrated that various materials—including Super EBA, MTA, IRM®, Retroplast, Endosequence®, and gutta-percha—have been effectively employed. The follow-up periods ranged from 6 months to 17.5 years, and the included studies encompassed randomized clinical trials, non-randomized clinical trials, and descriptive designs.
The primary purpose of retrograde root-end filling materials is to create a durable and tight apical seal that prevents bacterial leakage and reinfection of the root canal system. Ideally, these materials should not only provide a hermetic seal but also possess antimicrobial properties and promote periapical tissue regeneration. While the selection of these materials should be based on solid scientific and clinical evidence, current endodontic practices are often influenced by a combination of historical precedents, expert opinions, and manufacturers’ claims, which may not always reflect the highest levels of evidence [59,60,61,62,63,64].
To enhance the clinical relevance of the findings, this review included only clinical studies. Although randomized controlled trials with extended follow-up are the gold standard, they are not always available for every new material or clinical situation. Thus, non-randomized trials and observational studies provide valuable real-world insights that bridge the gap between laboratory findings and practical clinical application [24,31]. These studies are particularly important when evaluating newer materials, as they may exhibit beneficial properties not found in conventional options.
Super EBA is a reinforced zinc oxide–eugenol (ZOE) cement recognized for its excellent sealing capacity, biocompatibility, and handling characteristics. Its formulation consists of 60% zinc oxide, 34% alumina, and 6% natural resin, along with a liquid phase containing 62.5% ortho-ethoxybenzoic acid (EBA) and 37.5% eugenol [65]. The original formulation—Stailine Super EBA—was later modified by the Harry J. Bosworth Company by replacing silica with alumina in the powder while maintaining the same liquid component [66].
Introduced in the 1970s, Super EBA was rapidly adopted due to its plasticity, which facilitated manipulation and placement. It adheres well to dentinal walls even under moist conditions, exhibits short setting times, and can bond to itself for incremental placement. Scanning electron microscopy studies have shown good marginal adaptation, with evidence of collagen fibers integrating into the material [67,68]. Mechanically, it offers high compressive and tensile strength, neutral pH, and low solubility [69].
Despite the presence of eugenol—a known cytotoxic agent—its release is minimized due to the reinforced nature of the cement. Cytotoxicity is mainly observed during the initial setting phase but decreases significantly once the material has hardened [70,71]. An in vivo study has confirmed excellent tissue compatibility, further supporting its clinical use [72]. Comparative studies suggest that Super EBA provides superior sealing compared to amalgam, gutta-percha, and glass ionomer cement [59,60]. However, longer-term follow-up studies are needed to fully evaluate its clinical performance and potential complications [73,74].
MTA has emerged as a preferred material in endodontics due to its excellent sealing ability, biocompatibility, and capacity to stimulate hard tissue formation. Its formulation includes tricalcium silicate, dicalcium silicate, and bismuth oxide for radiopacity [75,76]. Originally developed in the 1990s by Torabinejad et al., MTA is a bioceramic hydraulic cement derived from Portland cement, with bismuth oxide added to increase visibility on radiographs [77,78,79].
Upon mixing with sterile water at a 3:1 ratio, MTA undergoes a hydration reaction, forming calcium hydroxide and calcium silicate hydrate, and sets within approximately 165 min [80]. It maintains a high pH (10.2 to 12.5) that contributes to its antimicrobial activity [81]. To address esthetic concerns related to discoloration, white MTA was introduced in 2002 [82].
MTA is bioactive and capable of forming hydroxyapatite in physiological environments, promoting strong bonds with dentin and facilitating tissue remineralization [83,84]. It also possesses osteoconductive properties, supporting bone regeneration [85,86]. However, MTA is not without limitations. Its long setting time, high cost, and difficult handling are frequently cited drawbacks. Additionally, it lacks a solvent for easy removal and may be subject to washout during early setting phases [7]. Newer formulations, such as MTA Angelus and MTA Plus™, aim to mitigate these disadvantages through faster setting and improved handling [87,88].
Overall, MTA continues to demonstrate superior clinical performance in retrograde surgeries, with consistently high success rates [89]. Nevertheless, efforts are ongoing to improve its usability and reduce costs without compromising its biological and mechanical properties.
IRM® is another ZOE-based material that has been reinforced with 20% polymethyl methacrylate to improve its mechanical strength. Although its sealing ability and biocompatibility are well-documented, its biological activity is inferior to that of MTA [5]. Historically, IRM has served as a control material in comparative studies, due to its reliable performance and favorable clinical outcomes [90,91].
While IRM lacks the capacity to stimulate cementogenesis or hard tissue formation, its effectiveness derives from its physical sealing ability, which prevents microbial ingress. A study reported comparable success rates to MTA in the short term, although MTA remains superior in long-term regenerative outcomes [92]. Thus, while IRM continues to be a viable material in endodontic surgery, its use is generally more limited in contexts where biological interaction is critical.
Retroplast is a fluid resin-based compound containing aromatic or aliphatic dimethacrylate monomers. First introduced in 1984, Retroplast has been used as a root-end filling material with favorable outcomes in terms of sealing ability and biocompatibility [90,91]. It was demonstrated that Retroplast provides a durable seal, reducing the risk of reinfection by preventing microleakage. In an in vitro comparison of the sealing ability of MTA and Retroplast, both materials performed well; however, Retroplast was especially noted for its effective sealing under a stereomicroscope using Rhodamine B dye [90]. This study highlighted Retroplast’s ability to maintain a consistent seal over time, making it a reliable option for endodontic surgery.
The biocompatibility of Retroplast is also well-documented, which is critical for promoting favorable healing responses. Research on the healing potential of various endodontic materials, including Retroplast, has shown that its use in retrograde fillings supports tissue regeneration and repair [92,93,94]. Rud et al. found that Retroplast’s hydrophobic properties help maintain a dry environment, which enhances healing after surgery [92].
Although newer materials such as MTA and bioceramics have gained prominence due to their bioactivity and regenerative potential, Retroplast remains a viable alternative, given its established clinical success. Retroplast can achieve comparable outcomes to MTA in terms of sealing and healing, though its mechanical properties and resin-based composition may limit its bioactivity compared to more modern hydraulic materials [95]. While clinical evidence supports its use, further studies are necessary to fully evaluate its long-term performance and durability. Its composition also suggests potential for improved handling properties, which may enhance clinical outcomes [93].
Bioceramic materials, particularly calcium silicate-based formulations like EndoSequence®, are increasingly popular in endodontics due to their excellent sealing properties, biocompatibility, and ability to promote tissue regeneration. These materials are known for forming hydroxyapatite upon exposure to moisture, enhancing integration with surrounding tissues [96,97].
EndoSequence® (Brasseler, Savannah, GA, USA) is a calcium silicate-based bioceramic designed for root-end fillings, similar to materials like MTA and Biodentine®. Unlike traditional MTA, EndoSequence® incorporates calcium phosphate, making it a bioceramic known for its biocompatibility, bioactivity, and non-toxic characteristics. The combination of calcium silicate and calcium phosphate confers significant dimensional stability, and, being bio-inert, the material does not degrade over time or provoke adverse reactions [98].
A key advantage of EndoSequence® is its nanoparticle composition, which facilitates deeper penetration into dentinal tubules, improving the mechanical seal. This penetration is enhanced by moisture within the tubules, which accelerates the setting reaction. This moisture-activated reactivity makes EndoSequence® highly suitable for retrograde filling procedures, where moisture is common in the surgical field. The high alkaline pH generated by the material creates an antimicrobial environment conducive to healing and tissue regeneration. Furthermore, the bioceramic nature promotes hydroxyapatite formation, enhancing integration with surrounding tissues and creating a robust seal at the root apex [98,99].
A comparative study evaluating the penetration of various calcium silicate cements into dentinal tubules found that Biodentine® exhibited the greatest penetration (1.57 mm), while EndoSequence® demonstrated superior handling characteristics and consistent penetration (1.56 mm). ProRoot MTA showed lower penetration values (1.25 mm) but was noted to be more technique sensitive [100]. EndoSequence® also exhibits excellent radiopacity, aiding clinicians in visualization during radiographic assessment [101].
Numerous studies have highlighted the regenerative potential of bioceramic materials like EndoSequence®, demonstrating their ability to stimulate hydroxyapatite crystal formation upon moisture exposure. This fosters a chemical bond with dentin, which not only enhances sealing ability, but also promotes remineralization of surrounding hard tissues—an essential process for healing in root-end surgeries [102,103].
Clinical outcomes with calcium silicate-based cements such as EndoSequence®, Biodentine®, and ProRoot MTA have consistently demonstrated favorable results in terms of apical sealing, biocompatibility, and tissue healing. Their ability to form a bioactive interface with dentin has made them the materials of choice in root-end surgeries, where a tight seal and biological integration are critical for long-term success [104].
Additionally, EndoSequence® has been reported to generate a highly alkaline environment during early setting stages, which provides antimicrobial effects and stimulates new hard tissue and cementum formation, thereby supporting faster healing and improved patient outcomes [101].
Overall, bioceramic materials, particularly calcium silicate-based formulations like EndoSequence®, have gained widespread popularity in endodontics due to their ability to create strong seals, promote healing, and prevent microleakage. Their bioactivity, ease of handling, and ability to penetrate dentinal tubules make them preferred materials for endodontic treatments, particularly when durable and biocompatible support for healing and tissue regeneration is required [105].
Studies report high success rates for bioceramics in retrograde fillings, suggesting that they may outperform traditional materials in some aspects [5,106]. Nevertheless, while initial clinical results are promising, more extensive long-term studies are needed to evaluate their durability and performance compared to established materials such as MTA and IRM® [107].
Gutta-percha is the most used root canal obturation material due to its ease of manipulation, plasticity, and biocompatibility. It consists primarily of trans-1,4-polyisoprene (natural rubber), zinc oxide, heavy metal sulfates, and waxes. Although it provides a good seal when used with an appropriate sealer, gutta-percha lacks bioactivity and does not actively promote healing or stimulate regeneration of surrounding tissues. This makes it inferior to newer materials like MTA and bioceramics, which encourage hard tissue formation and hydroxyapatite development [108].
This systematic review has several limitations. First, the number of available clinical studies evaluating retrograde filling materials remains limited, which may affect the generalizability of the findings. Second, significant heterogeneity was observed among the included studies in terms of follow-up duration, surgical techniques, and outcome measures, which precluded quantitative meta-analysis. Additionally, some included studies lacked rigorous methodological design or complete reporting, which may have introduced bias in the interpretation of results.
While this systematic review highlights the effectiveness of the materials discussed, it is important to acknowledge that other materials, such as newer bioceramic formulations, were not included in this analysis. This gap indicates a need for future research to conduct meta-analyses to comprehensively evaluate the comparative effectiveness of these materials in root-end filling applications. Additional studies focusing on long-term follow-up could provide valuable data regarding the longevity and success of these materials in clinical practice. Furthermore, investigating the potential synergistic effects of combining different materials may yield insights that could lead to improved clinical outcomes [62,63].

5. Conclusions

The choice of root-end filling materials is crucial for the success of endodontic surgery. New bioceramic materials like MTA and Biodentine offer improved sealing, biocompatibility, and tissue regeneration compared to traditional materials, leading to better clinical outcomes. However, further long-term studies are needed to confirm their durability. Continued research and evidence-based selection will help clinicians optimize treatment success and patient recovery.

Author Contributions

Conceptualization, T.A., R.B. and N.K.; methodology, T.A., C.E.C.-S., N.K., R.B. and C.E.C.-S.; software, Z.A., L.H., R.B., N.K. and Y.H.; validation, T.A., N.K. and R.B.; formal analysis, C.E.C.-S., N.K. and R.B.; investigation, Z.A., L.H., R.B., C.N. and N.K.; resources, R.B; data curation, C.E.C.-S., N.K., C.N., L.H., R.B. and Y.H.; writing—original draft preparation, T.A., R.B. and C.E.C.-S.; writing—review and editing, Z.A., N.K., C.E.C.-S. and Y.H.; visualization, R.B.; supervision, Y.H.; project administration, Y.H.; funding acquisition, Y.H. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Dataset available on request from the authors.

Conflicts of Interest

The authors declare no conflicts of interest.

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Applsci 15 06461 g001
Figure 1. PRISMA flow diagram of study selection process.
Figure 1. PRISMA flow diagram of study selection process.
Applsci 15 06461 g001
Table 1. Detailed search strategy and terms used for the PubMed database.
Table 1. Detailed search strategy and terms used for the PubMed database.
SearchTerms
#1(Apicectomy OR endodontic surgery OR apicoectomy OR root-end resection OR root end resection OR root-end surgery OR surgical endodontic treatment OR microapical surgery OR periradicular surgery OR apical microsurgery)
#2(Pulpectomy OR
pulpotomy OR root canal therapy OR root filled tooth OR root filled teeth OR
endodontically treated tooth OR endodontically treated teeth OR root canal treatment OR root filling OR root canal therapy OR endodontic treatment)
#3(Bioceramic OR Biodentine OR mineral trioxide aggregate OR repair material)
#4#1 and #2 and #3
Table 2. Summary of the main characteristics of the studies included in the qualitative synthesis, including study design, sample size, materials tested, and outcome measures.
Table 2. Summary of the main characteristics of the studies included in the qualitative synthesis, including study design, sample size, materials tested, and outcome measures.
Study and YearType of StudyNumber of Patients Included (Number of Teeth Treated)Retrograde Root Filling UsedFollow-UpMain Results
Chong, 2003 [26]Randomized clinical trial108 patients
(108 teeth)		Intermediate Restorative Material (IRM) (Dentsply) Mineral trioxide aggregate (MTA) (Loma Linda University, CA, USA)24 monthsNo statistically significant differences were found between the materials.
Lindeboom, 2005 [27]Randomized clinical trial100 patients
(100 teeth)		IRM (Dentsply, Konstanz, Germany)
MTA (Dentsply)		1 yearNo statistically significant differences were found between the retrofilling materials.
Christiansen, 2008 [28]Randomized clinical trial44 patients
(52 teeth)		MTA (Dentsply) Gutta-percha12 monthsTeeth treated with MTA showed significantly higher healing rates.
Kim, 2008 [29]Randomized clinical trial227 patients
(263 teeth)		IRM (Dentsply)
Super Ethoxybenzoic Acid (Super EBA) (Harry J. Bosworth, Skokie, IL, USA)
ProRoot MTA (Dentsply)		24 monthsAll three filling materials showed successful outcomes.
Song, 2012 [30]Randomized clinical trial388 patients
(260 teeth)		Super EBA (Harry J. Bosworth Co.)
ProRoot MTA (Dentsply)		1 yearNo significant difference was observed.
Kruse, 2016 [31]Randomized clinical trial44 patients
(52 teeth)		ProRoot MTA White (Dentsply)
Gutta-percha		6 yearsThe study found a success rate for surgical endodontic retreatment in the MTA group.
da Silva, 2016 [32]Randomized clinical trial12 patients
(30 teeth)		Pozzolana Biologic Silva cement (experimental material)
MTA white (Angelus, Londrina, Brazil)		6 monthsBoth materials showed significant periradicular tissue regeneration.
Öğütlü, 2018 [33]Randomized clinical trial112 patients
(112 teeth)		MTA (Angelus)
Super EBA (Harry J. Bosworth Co.)		6 monthsApical surgery using SuperEBA and MTA achieved an 88.4% success rate.
Parmar, 2019 [34]Randomized clinical trial32 patients
(52 teeth)		MTA (Dentsply)1 yearCollagen membranes did not significantly enhance healing periapical lesions.
Bharathi, 2021 [35]Randomized clinical trial40 patients
(74 teeth)		MTA (Dentsply)Not specifiedPiezoelectric surgery reduced pain and swelling.
Salah, 2024 [36]Randomized clinical trial56 patients (56 teeth)MTA (Dentsply)
TotalFill (FKG Dentaire SA, La Chaux-de-Fonds, Switzerland)		12 monthsBoth MTA and TotalFill root-end filling materials demonstrated high success rates.
Gulsever, 2024 [37]Randomized clinical trial64 patients (64 teeth)MTA (Angelus)9 monthsRetrograde MTA obturation showed high success rates.
Dong, 2024 [38] Randomized clinical trial240 teethiRoot BP Plus (ENP)
iRoot SP (ENP)		12 monthsBoth materials demonstrated good clinical success.
Dhamija, 2024 [39]Randomized clinical trial32 patients (59 teeth)MTA (Dentsply)5 yearsMTA showed high clinical success.
Von Arx, 2007 [40]Non-randomized clinical trial194 patients (194 teeth)Super EBA (Harry J. Bosworth Co.)
MTA (Dentsply)		12 monthsMaterial used for retrograde filling was not significant.
Von Arx, 2010 [41]Non-randomized clinical trial353 patients (353 teeth)ProRoot (Dentsply)
Retroplast (Retroplast Trading, Rorvig, Denmark)		12 monthsMTA had statistically significant higher success.
Song, 2013 [42]Non-randomized clinical trial135 patients (199 teeth)Super EBA (Harry J. Bosworth)
ProRoot MTA (Dentsply)		7 yearsBoth materials achieved higher success rates.
Von Arx, 2014 [43]Non-randomized clinical trial271 patients (271 teeth)ProRoot (Dentsply)
Retroplast (Retroplast Trading, Skaidiškės, Lithuania )		5 yearsThe overall rate of healed cases was significantly higher for MTA.
Tortorici, 2014 [44]Non-randomized clinical trial843 patients (938 teeth)MTA (ProRoot, Charlotte, NC, USA)5 yearsThe use of MTA demonstrated significantly higher clinical success rates.
Von Arx, 2020 [45]Non-randomized clinical trial146 patients (170 teeth)TotalFill® (Brasseler, Georgetown, Georgia )1 yearRetrograde healing achieved a 94.1% success rate.
Kaur, 2024 [46]Non-randomized clinical trial45 patients (45 teeth)Gutta-percha
Retroplast (Endoplast)
DiaRoot BioAggregate (Dia Dent, Cheongju-si, Republic of Korea)		16 monthsThere
was no significant difference in the clinical outcome after endodontic surgery.
Wang, 2017 [47]Cohort81 patients (74 teeth)ProRoot MTA (Dentsply)12 to 30 monthsThe study found a 90.5% rate of complete healing in teeth.
Ramis-Alario, 2022 [48]Cohort298 patients (57 teeth)MTA (Dentsply)2 yearsThe study found a 93% success rate 2 years after endodontic microsurgery.
Yoo, 2024 [49]Retrospective cohort362 patients (309 teeth)ProRoot MTA (Dentsply Sirona)10–17.5 yearsLong-term healing and survival after endodontic microsurgery were significantly influenced by the preoperative status of the tooth.
Liu, 2024 [50]Retrospective cohort74 patients
(74 teeth)		iRoot BP Plus (Innovative Bioceramix, Burnaby, BC, Canada)6 yearsThe apical barrier technique using premixed calcium silicate-based putty showed high long-term success.
Saunders, 2008 [51]Cross-sectional321 patients (321 teeth)Proroot MTA White (Dentsply)12 monthsThe overall success rate for MTA was 88.8%.
Pantchev, 2009 [52]Cross-sectional131 patients (186 teeth)Super EBA (Staident International, Tokyo, Japan)4 yearsSuper EBA cement achieved high success rates.
Shinbori, 2015 [53] Cross-sectional94 patients (113 teeth)EndoSequence BC Root Repair (Brasseler)1 yearMicrosurgery resulted in a 92% overall success rate.
Shen, 2016 [54] Cross-sectional97 patients (128 teeth)MTA (Dentsply)1 yearMicrosurgical techniques and MTA resulted in a 57.7% success rate.
Sutter, 2019 [55]Cross-sectional81 patients (81 teeth)Super EBA (Staident International)
MTA (Dentsply)		1 yearA statistically reasonable evaluation of the impact of the filling material was not feasible.
Truschnegg, 2019 [56]Cross-sectional73 patients (87 teeth)IRM (Dentsply)13 yearsIRM as a filling material demonstrates good performance after 10–13 years.
Van, 2020 [57]Cross-sectional24 patients (22 teeth)MTA (Angelus)1 yearAfter treatment, bone defect volume reduction was observed.
Stueland, 2022 [58]Cross-sectional1157 patients (351 teeth with non-surgical retreatment and 107 teeth with endodontic microsurgery)Most retrograde fillings were with bioceramic materials, only two cases had IRM (Dentsply)>36 monthsMicrosurgical apicectomy and retrograde filling outperformed non-surgical retreatment for apical periodontitis.
Yamada, 2024 [59]Cross-sectional46 patients (46 teeth)ProRoot MTA White (Dentsply)12 monthsEndodontic microsurgery showed a 93.5% success rate after 1 year.
Flórez, 2024 [60] Cross-sectional52 patients (52 teeth)MTA (Dentsply)
Super EBA (Staident International)
Biodentine (Septodont, Saint-Maur-des-Fossés, France)		12 monthsThe overall success rate was 78.84%.
Table 3. Risk of bias assessment of the included randomized clinical trials using the Cochrane Risk of Bias Tool (RoB 2.0).
Table 3. Risk of bias assessment of the included randomized clinical trials using the Cochrane Risk of Bias Tool (RoB 2.0).
StudyRandomizationDeviations from the Intended InterventionsMissing Outcome DataMeasurement of the OutcomeSelection of the Reported Result
Chong, 2003 [26]LowLowLowLowLow
Lindeboom, 2005 [27]HighLowLowLowLow
Christiansen, 2008 [28]LowLowLowLowLow
Kim, 2008 [29]LowHighHighHighHigh
Song, 2012 [30]LowLowHighLowLow
da Silva, 2016 [32]LowLowHighHighHigh
Kruse, 2016 [31]LowLowLowLowLow
Öğütlü, 2018 [33]LowLowLowLowLow
Parmar, 2019 [34]LowLowLowLowLow
Bharathi, 2021 [35]LowLowLowLowLow
Salah, 2024 [36]LowLowLowLowLow
Gulsever, 2024 [37]HighLowLowLowLow
Dong, 2024 [38] LowLowLowLowLow
Dhamija, 2024 [39]HighLowLowLowLow
Table 4. Risk of bias assessment of the included non-randomized clinical trials using the Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) tool.
Table 4. Risk of bias assessment of the included non-randomized clinical trials using the Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) tool.
StudyConfoundingSelection of
Participants
for the Study		Classification of
Interventions		Deviations
from Intended
Interventions		Missing DataMeasurement
of Outcomes		Selection of
the Reported
Result
Von Arx, 2007 [40]LowLowLowLowLowLowLow
Von Arx, 2010 [41]LowLowLowLowLowLowLow
Song, 2013 [42]LowLowLowLowLowLowModerate
Von Arx, 2014 [43]LowLowLowLowLowLowLow
Tortorici, 2014 [44]ModerateLowLowModerateLowLowLow
Von Arx, 2020 [45]LowLowLowLowLowLowLow
Kaur, 2024 [46]LowLowLowLowLowLowModerate
Table 5. Risk of bias assessment of the included cohort studies using the Newcastle–Ottawa Scale (NOS).
Table 5. Risk of bias assessment of the included cohort studies using the Newcastle–Ottawa Scale (NOS).
StudySelectionComparabilityOutcomeTotal
Representativeness of the Exposed CohortSelection of the Non-Exposed CohortAscertainment of ExposureOutcome of Interest Not Present at the Start of the StudyComparability of Cohorts on the Basis of the Design or AnalysisAssessment of OutcomeDuration of Follow-UpAdequacy of Follow-Up
Wang, 2017 [47]111100116
Ramis-Alario, 2022 [48]111100004
Yoo, 2024 [49]111000115
Liu, 2024 [50]111100004
Table 6. Quality assessment of the included cross-sectional studies using the Joanna Briggs Institute (JBI) critical appraisal checklist.
Table 6. Quality assessment of the included cross-sectional studies using the Joanna Briggs Institute (JBI) critical appraisal checklist.
StudyQ1Q2Q3Q4Q5Q6Q7Q8Score
Saunders, 2008 [51]YYYYNNYY6
Pantchev, 2009 [52]YYYYNNYY6
Shinbori, 2015 [53]NYYYNNYN4
Shen, 2016 [54]YYYYNNYY6
Sutter, 2019 [55]YYYYNNYY6
Truschnegg, 2019 [56]UUYYNNYY4
Van, 2020 [57]YYYYNNYN5
Stueland, 2022 [58]YYYYNNYN5
Yamada, 2024 [59]NYYYNNYN4
Florez, 2024 [60] YYYYNNYY6
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Ashi, T.; Bourgi, R.; Cuevas-Suárez, C.E.; Hardan, L.; Nahat, C.; Altaqi, Z.; Kharouf, N.; Haikel, Y. Healing Ability of Endodontic Filling Materials in Retrograde Treatment: A Systematic Review of Clinical Studies. Appl. Sci. 2025, 15, 6461. https://doi.org/10.3390/app15126461

AMA Style

Ashi T, Bourgi R, Cuevas-Suárez CE, Hardan L, Nahat C, Altaqi Z, Kharouf N, Haikel Y. Healing Ability of Endodontic Filling Materials in Retrograde Treatment: A Systematic Review of Clinical Studies. Applied Sciences. 2025; 15(12):6461. https://doi.org/10.3390/app15126461

Chicago/Turabian Style

Ashi, Tarek, Rim Bourgi, Carlos Enrique Cuevas-Suárez, Louis Hardan, Carmen Nahat, Zaher Altaqi, Naji Kharouf, and Youssef Haikel. 2025. "Healing Ability of Endodontic Filling Materials in Retrograde Treatment: A Systematic Review of Clinical Studies" Applied Sciences 15, no. 12: 6461. https://doi.org/10.3390/app15126461

APA Style

Ashi, T., Bourgi, R., Cuevas-Suárez, C. E., Hardan, L., Nahat, C., Altaqi, Z., Kharouf, N., & Haikel, Y. (2025). Healing Ability of Endodontic Filling Materials in Retrograde Treatment: A Systematic Review of Clinical Studies. Applied Sciences, 15(12), 6461. https://doi.org/10.3390/app15126461

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