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SYSTEMATIC REVIEW article
Front. Dent. Med , 21 January 2025
Sec. Endodontics
Volume 5 - 2024 | https://doi.org/10.3389/fdmed.2024.1498353
This article is part of the Research Topic Integrated Inflammology in Endodontics View all 3 articles
Introduction: Biodentine is a well-known endodontic material that is applied in various endodontic therapies. Enterococcus faecalis (E. faecalis) is associated with endodontic failure and persistent periapical infection. The purpose of this systematic review was to summarize the available evidence regarding the antibacterial activity of Biodentine against E. faecalis and to compare it to other commercial endodontic materials.
Methods: An electronic search of literature was conducted in PubMed, Scopus, Web of Science, and Google Scholar in addition to a manual search in specialized journals up to May 2024. The eligibility criteria, data extraction, and evaluation of risk of bias were assessed by two independent authors. The risk of bias was evaluated in accordance with Modified CONSORT checklist items for pre-clinical in vitro studies on dental materials.
Results: Out of 343 studies, thirty-seven fulfilled the inclusion criteria and were included in this review. Thirty studies reported a good antibacterial efficacy of Biodentine against E. faecalis. Biodentine was superior to or, at least, as efficacious as MTA, MTA Angelus, GIC, RMGIC, DiaRoot BioAggregate, NeoPutty, iRoot FS, MTA Repair HP, MTA Biorep, Well-Root PT, Activa, NeoMTA 2, Calcimol LC, TotalFill, and IRM. The findings were supported by studies with medium to high risk of bias (low quality).
Conclusions: Considering the limitations of this systematic review, there is accumulating evidence on the antibacterial activity of Biodentine against E. faecalis in context of endodontics. However, randomized clinical trials with well-designed and robust methodologies are required in order to provide information about its clinical behaviour.
The success of endodontic treatment relies on an accurate diagnosis and a definitive treatment plan (1). Oral bacteria have a significant role in the development and progression of pulpal and periapical diseases, as well as in the failure of endodontic treatment (2). Most inflammatory pulpal and periapical diseases are initially treated with conservative nonsurgical treatments (3). Inadequate cleaning of the root canal and persistent/secondary intraradicular infection attributes to re-infection of the root canal, and leads to endodontic failure (4). Surgical intervention (such as apicoectomy and retrograde filling) becomes necessary to save the tooth when nonsurgical treatments have failed (3).
Certain bacteria are frequently found in infected root-filled teeth (5). E. faecalis is commonly detected in the cases of failed endodontic treatment (5), with a percentage rate of 77% (6). E. faecalis is a facultatively anaerobic Gram-positive coccus (7) that exhibits high resistance to antimicrobial agents and tolerates low-nutrient and highly alkaline environments (7–9). In addition, it has the ability to penetrate dentinal tubules (10) and form biofilms on the root canal walls (11).
Following endodontic treatment of chronic periodontal disease, E. faecalis is often associated with persistent intra-radicular and extra-radicular infections (12), although recent evidence indicates that it is not considered the key pathogen in root canal infection (13). The short-term application of intracanal dressing is often insufficient in eradicating bacteria, as the medicament fails to reach the intended sites (14). Furthermore, the inflammation can be efficiently reduced by antibiotics in acute or chronic apical periodontitis (15); however, a complete relief is often hindered by the presence of unreachable bacteria within the canal system (16).
Surgical intervention is the treatment of choice if conventional endodontic treatment/re-treatment fails to save the tooth. This approach involves the removal of persistent pathogens by debridement of infected periradicular tissue, resection of root-end (apicoectomy), and obturation of retrograde root canal (root-end filling) (17). If there are remaining intracanal bacteria, the tight root-end filling will seal the apical termination of root canal and encases the remaining bacteria (18). Therefore, it is important for the root-end filling materials to have antibacterial properties.
Biodentine is one of the well-known root-end filling materials which has drawn attention in recent years. It was introduced by Septodont in 2009 as a dentin replacement material. The powder consists of tricalcium, dicalcium silicate, calcium carbonate and oxide filler, iron oxide shade, and zirconium oxide (as radiopacifier). The liquid mainly contains calcium chloride in an aqueous solution (as an accelerator) with an admixture of hydrosoluble polymer (as a water reducing agent) (19). The hydration of the calcium silicate components leads to the formation of calcium silicate hydrate and calcium hydroxide, the latter of which directly promotes antimicrobial effects (20). The studies have shown that Biodentine is biocompatible (21), stimulates odontoblast differentiation (22) and reparative dentin formation (23, 24), and has an adequate sealing ability (25). Therefore, Biodentine is considered a suitable material for application in various endodontic therapies including surgical endodontics (19).
Many studies have investigated the antibacterial activity of this material against E. faecalis. However, there is a conflicting overview of the existing findings to determine the effectiveness of Biodentine against E. faecalis. This review aims to systematically summarize the available evidence on the antibacterial activity of Biodentine material against E. faecalis and to compare it to other commercial endodontic materials.
The following PICOS guided the formulation of the research question: P (population): Bacterial cultures of E. faecalis; I (intervention): Biodentine; C (comparators) commercial endodontic materials; O (outcomes) Inhibition or reduction in bacterial growth; S (study design) all relevant in vitro and in vivo studies. Based on the PICOS components, the review question is: Is Biodentine effective in inhibiting the growth of E. faecalis, and how does its effectiveness compare to that of other commercial endodontic materials?
The null hypothesis for this review is: Biodentine exhibits antibacterial activity against E. faecalis that is not significantly different from, or superior to, other commercial endodontic materials.
This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) (26).
A comprehensive literature search was conducted in March 2024 (and updated in May 2024) in four electronic databases, PubMed, Scopus, Web of Science, and Google Scholar, for the studies published since 2009 (the date of Biodentine introduction) up to May 2024. A combination of search keywords and Medical Subject Headings (MeSH) terms with Boolean operators (AND, OR) was used, as shown in Table 1. In addition, a manual search was conducted in the following dental materials- and endodontics-related journals: International Endodontic Journal, Journal of Endodontics, Australian Endodontic Journal, Endodontology, Dental Materials, Dental Materials Journal, and Oral Surgery, Oral Medicine, Oral Pathology, and Oral Radiology, to find out articles that did not appear in the electronic search of the above database outcome.
This review included all the studies in the English language, conducted in vivo on both human and animal subjects as well as in vitro on any type of laboratory model.
Studies were excluded based on the following criteria: studies that evaluated the antibacterial activity of Biodentine against bacterial species other than E. faecalis; studies that investigated the response of E. faecalis to endodontic materials other than Biodentine; studies involving E. faecalis mixed with other bacterial species; studies assessing modified versions of Biodentine; studies that examined the dentin/Biodentine interface; and review studies, case reports, and case series.
In accordance with PRISMA guidelines, two authors (HS and NS) independently screened the included articles and extracted the necessary information. Initially, the title and abstract of each article were assessed and the appropriate studies were retrieved and then thoroughly and carefully examined for eligibility and inclusion in the review. EndNote X8 (Clarivate Analytics, PA, USA) was used to eliminate all duplicated studies and manage the study citations list. In a case of discrepancy between the authors, a discussion was done with a third author (AT) and came to a decision. After screening the included studies, the following data were extracted: authors, year and type of study, type of Biodentine intervention, type of Biodentine samples, E. faecalis strain, assessment method, exposure time, main results, and conclusion.
A narrative synthesis was performed to address the diversity in study designs, interventions, and outcomes. The studies were categorized based on their methodologies, type of Biodentine intervention, and the results of the antibacterial activity against E. faecalis. The findings were qualitatively summarized, with a focus on identifying shared patterns and notable discoveries across the studies.
The quality and risk of bias of the included studies were assessed independently by two authors (HS and SA) in accordance with Modified CONSORT checklist items for pre-clinical in vitro studies on dental materials [Figgion et al. (27)]. The criteria included eight domains: intervention, outcomes, sample size calculation, specimen randomization, implementation, operator blinded, statistical analysis, and results (outcomes and estimation). During the assessment process, each domain was reported as YES if the corresponding parameter was explicitly described or NO if the parameter was absent or not fully declared. The third author (AT) resolved the discrepancy between the two authors. The overall risk of bias for each study was determined based on the number of “YES” as: 1–3 refers to high bias; 4–6 refers to medium bias; and 7–8 refers to low bias.
The search in electronic databases retrieved a total of 343 articles [PubMed = 66, Scopus = 83, Web of Science = 62, Google scholar = 120 (top 120 relevant studies), and hand searching in journals = 12]. By the electronic de-duplication, 148 studies were excluded. Then, an independent and comprehensive reading of the titles and abstracts of the remaining 195 articles were performed and 155 articles which did not meet the inclusion criteria were excluded. After retrieving the articles and thoroughly examined them for inclusion and eligibility, three articles were excluded with reasons. Finally, the remaining 37 studies that fulfilled the inclusion criteria were included in this review study. The excluded full-text articles (n = 3) were due to the following reasons: E. faecalis was mixed with other bacterial species forming dual and multispecies biofilm models (28); A modified Biodentine was used in the antibacterial activity assessment (29); and the absence of a pure Biodentine control (30). The strategy search in the electronic database in this review study has been summarized in Figure 1.
As illustrated in Table 2, none of the included studies met all the criteria of risk of bias. Of the 37 studies in this systematic review, only 5 studies (13.51%) had a medium risk of bias, whereas the remaining 32 studies (86.48%) showed a high risk of bias. Most of the studies failed or did not clearly describe the sample size calculation, specimen randomization, implementation, and operator blinded parameters.
Table 2. Risk of bias of the studies in accordance with modified CONSORT checklist [figgion et al. (27)].
The characteristics and details of the included studies are summarized in Table 3. All the 37 studies included in this review article were in vitro studies (31–67) and no in vivo studies were found. Of these studies, twenty-three studies employed an agar diffusion test (ADT) for assessing the antibacterial activity (32–38, 40–46, 49, 51, 58, 60, 62–66) by measuring the inhibition zone around the test material. Three studies used direct contact test (DCT) to count the colony forming units (CFUs) (39, 61) or optical density (OD) (54). Three studies used antibiofilm assay reading the OD (47, 57) or Log (CFU + 1)/ml (56) of adherent stained biofilm. Two studies used the tube dilution method (48, 52), recording the minimal inhibitory concentration (MIC), and one study used bacterial adhesion assay (55) by a confocal laser scanning microscope to image the viable bacteria. One used the broth dilution method (53) to read the OD. The study by Ji et al. (50) used three methods, ADT, DCT, and carry-over effect test, while Nourzadeh et al. (59), and Koutroulis et al. (67), used the dentine block model to test the antibacterial activity of test materials and CFUs were counted. The study by Cruz Hondares et al. (31), employed two methods, ADT and direct culture test.
Twenty-three studies investigated the antibacterial activity of Biodentine compared to other commercial endodontic materials such as MTA Biorep, Well-Root PT, TheraCal LC, Theracal PT, Dycal, Calcimol LC, Activa, iRoot FS, Endosequence root repair material (ERRM), ProRoot MTA, MTA Angelus, MTA, MTA Repair HP, NeoMTA Plus, NeoMTA 2, NeoPutty, White-MTA Flow, MTA Plus, GIC, RMGIC, Rootdent MTA, DiaRoot BioAggregate and Calcium-enriched mixture (CEM) (31, 32, 35, 39–46, 48–54, 57, 59, 60, 65, 66), whereas fourteen studies investigated the antibacterial activity of Biodentine as a control/reference material compared to experimental materials (33, 34, 36–38, 47, 55, 56, 58, 61–64, 67).
Of the thirty-seven studies included in this review article, thirty studies reported a good antibacterial activity of Biodentine against E. faecalis (32–34, 36, 38–43, 45–49, 51–59, 61–66), one study reported a limited antibacterial activity of Biodentine (37), four studies reported a conflicting antibacterial activity, whereas Ji et al. (50) study exhibited no bacterial inhibition for Biodentine using ADT and carry-over effect test while a good antibacterial activity was shown using DCT, Cruz Hondares et al. (31) found no antibacterial activity using ADT, while a significant inhibitory effect was detected using direct culture test, a study by Çırakoğlu et al. (44) revealed no bacterial inhibition at 24 h while a limited antibacterial activity was found at 48 h, and a study by Koutroulis et al. (67) revealed antibacterial activity at 24 h, while no bacterial count reduction was observed at 28 days. Only two studies reported negative antibacterial activity of Biodentine against E. faecalis using both ADT and DCT (60) and ADT (35).
The antibacterial activity of Biodentine at various time intervals has been conducted in thirteen studies (32, 35, 40, 44, 45, 48, 51, 54, 58–60, 66, 67). In three studies, there was no statistically significant difference (p > 0.05) in the antibacterial activity of Biodentine against E. faecalis at different time intervals (40, 48, 66). Other studies reported an increased antibacterial activity (P < 0.01) at 30 days compared to 7 days (59), and at 48 h compared to 24 h (44). However, a reduction was reported in two studies at 72 h compared to 12, 24, and 48 h (P < 0.001) (45), and in 24 h compared to 28 days (p < 0.05) (67). One study (32) reported increased antibacterial activity at 48 h compared to 24 h, followed by a decrease at day 7 (p = .012). The level of Biodentine's antibacterial activity remained nearly in same level across three other studies (51, 54, 58), while two studies reported no antibacterial activity (35, 60).
The antibacterial activity of different time interval-aged Biodentine against E. faecalis has been shown in two studies (55, 56). A study by Koutroulis et al. (55) revealed no significant difference (p > 0.05) in the antibacterial activity of Biodentine aged for 1, 7, and 28 days in water or FBS. While, a study by Koutroulis et al. (56) found that bacterial inhibition in water leachates increased over time when the medium was not refreshed (days 7–28) but decreased when the medium was changed. However, FBS leachates demonstrated lower antibacterial activity compared to water leachates.
Eleven studies investigated the antibacterial efficacy of Biodentine compared to MTA against E. faecalis (31, 35, 41, 42, 48–51, 57, 62, 63). The studies reported a significant (p < 0.05) superiority of Biodentine in killing E. faecalis in 3 studies (48, 49, 63), and non-significantly (p > 0.05) in 5 studies (31, 41, 42, 50, 51), which indicates a clinical reduction in bacterial growth. Whereas, Biodentine was inferior in bacterial inhibition compared to MTA in 2 studies, significantly (p < 0.05) in one study (62), and non-significantly (p > 0.05) in one study (57). A study by Akin et al. (35) demonstrated no antibacterial efficacy for Biodentine and MTA after a complete setting reaction.
The comparison of Biodentine and MTA Angelus against E. faecalis appeared in 13 studies. Biodentine exhibited significantly (p < 0.05) greater antibacterial activity in 8 studies (31, 33, 34, 36, 43, 45, 46, 52) and non-significantly (p > 0.05) in 2 studies (64, 65), whereas MTA Angelus exhibited significantly (p < 0.05) greater antibacterial activity in one study (40) and non-significantly (p > 0.05) in 1 study (47). One study (54) reported lower (p > 0.05) antibacterial activity for Biodentine at immediate time point and day 1, and higher (p > 0.05) activity at 1 week compared to MTA Angelus.
Four studies investigated the effectiveness of MTA Plus and Biodentine against E. faecalis (47, 48, 57, 66). Of these studies, two studies (48, 66) reported better antibacterial activity (p < 0.05) for Biodentine compared to MTA Plus. Whereas, two studies (47, 57) showed that MTA Plus was superior to Biodentine with no significant difference (p > 0.05). Two studies evaluated the effectiveness of CEM in comparison to Biodentine against E. faecalis (46, 59). One study (46) reported significantly (p < 0.05) better antibacterial activity for Biodentine, and one study (59) reported that Biodentine was significantly (p < 0.05) inferior compared to CEM. In addition, of the 3 studies investigated ERRM in comparison to Biodentine against E. faecalis (31, 51, 66). Biodentine exhibited significantly (p < 0.05) better antibacterial activity in one study (66), and non-significantly (p > 0.05) in one study (31); whereas, one study (51) reported that ERRM had significantly (p < 0.05) better antibacterial activity than Biodentine.
The antibacterial activity of Biodentine compared to IRM was reported in three studies (55, 56, 67). In two studies (55, 67), Biodentine demonstrated antibacterial activity similar (p > 0.05) to that of IRM. In the other study (56), Biodentine exhibited statistically higher antibacterial activity in leachates prepared over 28 days without a medium change, similar activity to IRM in leachates prepared over 28 days with weekly medium changes, and lower antibacterial activity in leachates prepared in the cell culture insert (0–24 h). One study by Koutroulis et al. (67), compared the antibacterial activity of Biodentine and TotalFill, finding that both exhibited similar (p > 0.05) antibacterial effects at 1 and 28 days.
Four studies evaluated TheraCal LC against E. faecalis and compared to Biodentine (35, 40, 52, 53). One study (52) showed that Biodentine had greater antibacterial activity than TheraCal LC, with no significant difference (p > 0.05). Whereas TheraCal LC had significantly (p < 0.05) better antibacterial activity in one study (40) and non-significantly (p > 0.05) in one study (53). Furthermore, the study by Akin et al. 2024 (35) reported no antibacterial activity for TheraCal LC and Biodentine after the complete setting reaction. Additionally, the antibacterial activity of Biodentine was compared to Dycal in 4 studies (32, 35, 40, 54). Biodentine had significantly (p < 0.05) greater antibacterial activity than Dycal at different time intervals in one study (32). In addition, Biodentine was non-significantly (p > 0.05) superior in inhibiting bacterial growth immediately and 24 h and significantly (p < 0.05) at 1 week in one study (54), whereas, Dycal had significantly (p < 0.05) higher antibacterial activity in one study (40) at 24 h and 48 h. The study by Akin et al. (35) revealed no antibacterial activity for Dycal and Biodentine after a complete setting reaction. Furthermore, the antibacterial efficacy was significantly (p < 0.05) superior in Biodentine compared to GIC (42), RMGIC (43), DiaRoot BioAggregate (45), NeoPutty (31), and iRoot FS (50). Biodentine had greater antibacterial activity with non-significant differences (p > 0.05) compared to MTA Repair HP (44), MTA Biorep (39), Well-Root PT (39), Activa (40), NeoMTA 2 (31), and Calcimol LC (40). Finally, the antibacterial activity was significantly (p < 0.05) inferior in Biodentine compared to Theracal PT (53), Rootdent MTA (32), and Zinc polycarboxylate cement (37).
Endodontic failure is generally attributed to the lack of proper cleaning of the root canal system and leakage of bacteria into the periradicular tissues. When the infection persists after endodontic treatment/re-treatment, an apicoectomy is indicated and a root-end filling material is placed to prevent re-infection of the root canal. Therefore, the antibacterial activity of endodontic materials is essential for the treatment success in order to prevent or delay infection and extend the lifetime of restorations. Biodentine, a calcium silicate-based material, has gained popularity in recent years due to its various clinical applications, including root-end filling procedures (69, 70). However, there is a shortage of studies and conflicting results regarding the antibacterial activity of Biodentine (71).
E. faecalis is an anaerobic bacterium associated with endodontic failure and persistent periapical infection (72). Although it is not part of the root canal system's microbial flora (73), it is discovered in the oral cavity from contaminated food. It was suggested that this bacterium penetrates the root canal system through several ways, including the lack of coronal seal after root canal treatment, dentinal fractures, carious progression in contiguity with the root canal system during pulp necrosis or inflammation, bloodstream, and through root fracture or lateral canals (74). This species has been reported to exhibit varying degrees of resistance to several antimicrobial agents (75) and intracanal dressings such as calcium hydroxide (76), making its eradication from the root canals challenging. This review focused on the studies that investigated the antibacterial activity of Biodentine against E. faecalis, as it is one of the main bacteria and most commonly involved in studies on persistent periapical infections (13). Although a recently published review article (71) identified the antimicrobial efficacy of Biodentine, it provided brief coverage and limited details regarding its specific efficacy against E. faecalis.
The current review revealed that Biodentine has good antibacterial activity against E. faecalis, with thirty out of 37 included studies reporting positive effectiveness. One study exhibited limited effectiveness, four showed conflicting results, and only two demonstrated negative effectiveness. The outcomes of the included studies appear to have minor discrepancies likely due to their different methodologies such as assessment methods, concentration of the microorganism, and the amount of test materials. The result of ADT is semi-quantitative and depends on the solubility and diffusability of the material within the agar medium (77). Solid endodontic materials may not be diffusible (50). The carry-over effect may also be affected by the insolubility of the material (50). Whereas DCT is a quantitative and reproducible method allowing testing of water-insoluble materials and accurately mimics the contact between the materials and microorganisms (54, 77). It demonstrates the material's bactericidal or bacteriostatic effects regardless of its diffusibility in the medium (78). Therefore, ADT is less sensitive in evaluating the antibacterial activity of calcium silicate-based cement compared to direct culture test (31) and DCT (50), which explains the conflicting outcomes between the ADT and other evaluating methods in the same study.
The antibacterial effect of Biodentine is mainly attributed to its alkalinity and calcium release. The cement hydration process generates a colloidal gel and releases calcium hydroxide, which inhibits bacterial growth. Additionally, as Biodentine sets, its pH rises to 12.5 which prevents bacterial growth and disinfects the surrounding area (46, 79). Moreover, it was reported that Biodentine inhibits microbial adherence, resulting in a strong antibacterial activity (79).
For the persistence of the antibacterial activity of Biodentine at different time intervals, conflicting evidence was reported among the included studies, where 3 out of 13 studies demonstrated statistical similarities over time, 2 demonstrated an increase in antibacterial activity, and 3 demonstrated nearly the same level. One demonstrated an increase followed by a decreased antibacterial activity. While a reduction was reported in 2 studies, and no bacterial inhibition in 2 studies. The antibacterial activity of Biodentine against E. faecalis appears to be influenced by both aging time and the medium used, with conflicting results between studies. One study exhibited no difference in antibacterial activity across different aging periods in either water or FBS, while another study found that bacterial inhibition in water leachates increased over time when the medium was not refreshed but decreased when refreshed. Additionally, FBS leachates showed lower antibacterial activity compared to water.
This review revealed that Biodentine was superior to or, at least, as efficacious as several commercial endodontic materials against E. faecalis such as MTA [in 8 (31, 41, 42, 48–51, 63) out of 11 studies], MTA Angelus [in 11 (31, 33, 34, 36, 43, 45, 46, 52, 54, 64, 65) out of 13 studies], GIC (42), RMGIC (43), DiaRoot BioAggregate (45), NeoPutty (31), iRoot FS (50), MTA Repair HP (44), MTA Biorep (39), Well-Root PT (39), Activa (40), NeoMTA 2 (31), Calcimol LC (40), TotalFill (67), and IRM (55, 56, 67). Whereas, the antibacterial activity of Biodentine was inferior to Theracal PT (53), Rootdent MTA (32), and Zinc polycarboxlate cement (37). Furthermore, it was not feasible to reach a summary on the comparative antibacterial effects of Biodentine in comparison to MTA Plus, CEM, ERRM, TheraCal LC, and Dycal because of the conflicting results among the included studies.
The current evidence indicates that Biodentine is a superior material in endodontic treatment with potent antibacterial activity against E. faecalis. However, this evidence lacks a sufficient clinical base to support Biodentine for routine use in inhibiting E. faecalis growth. All the included studies and collected data were in vitro, which is unreliable in determining Biodentine's clinical potential. Although in vitro studies with high-quality and well-designed methodology offer helpful solutions for clinical issues, randomized controlled clinical trials reveal the most dependable and robust outcomes (80). Another limitation of this review was the use of various antibacterial assessment methods (such as ADT, DCT, antibiofilm assay, tube dilution method, bacterial adhesion assay, broth dilution method, carry-over effect test, direct culture test, and dentine block model), and heterogeneity in their procedures among the studies [such as bacterial strains, evaluation times, amount of test materials sample, and various measurements (CFUs and OD) used in DCT and antibiofilm assay]. The lack of standardization and evaluation criteria among the included studies caused the cross-study comparison to be hard to execute, and ultimately conducting a meta-analysis was not practical (81). It is important to highlight the necessity of developing standardized methods for the evaluation of antibacterial activity. A further limitation was that some studies examined the antibacterial activity of Biodentine on planktonic bacteria (such as tube dilution method, broth dilution method, direct culture test, and carry-over effect test). This model does not closely resemble in vivo or clinical circumstances because the bacteria are present as complex biofilm communities in the oral cavity (82). Contrastingly to planktonic cells, biofilm structures provide resistance against antimicrobial agents as bacteria are embedded in a hydrated polymeric matrix that serves as a shield to protect bacterial growth (83, 84). The methodological quality evaluation in this review indicated that the findings were supported by studies with medium to high risk of bias (low quality). Lastly, even though the protocol of this study was not registered, the PRISMA guidelines were strictly followed.
This review provides several key strengths that enhance the validity and reliability of the study, including a comprehensive literature search in reputable databases that ensures a broad coverage of relevant studies. The review also employed clear eligibility criteria and rigorously evaluated the risk of bias using the Modified CONSORT checklist items for pre-clinical in vitro studies on dental materials, to ensure the reliability of the findings. In addition, it offers a comparative analysis of Biodentine's antibacterial effect relative to other commercial endodontic materials against E. faecalis, providing a more relevant understanding of Biodentne's relative efficacy in clinical practice. Finally, the main finding of this study, the strong antibacterial activity of Biodentine in inhibiting the growth of E. faecalis, was strongly supported by a substantial number of studies demonstrating favorable effects against E. faecalis. This consistent evidence highlights the Biodentine's significant potential as an endodontic material and supports the acceptance of the null hypothesis of the review.
The results of this systematic review suggest that Biodentine's strong antibacterial activity against E. faecalis has significant implications for clinical practice. Clinicians can confidently use Biodentine to help prevent bacterial infection, promote healing, and improve treatment outcomes, particularly in cases with persistent or resistant infections. In addition, it may help prevent re-infection and treatment failure in these cases. Its use could also aid in reducing inflammation, leading to faster recovery time and fewer post-treatment complications, such as post-operative infections or flare-ups, thereby enhancing endodontic treatments. Its comparability or superiority to other materials, such as MTA and GIC, supports its potential as a preferred choice in clinical applications, including root-canal sealing and apical surgery. This is further reinforced by its favorable biological and physicochemical properties, as well as its cost-effectiveness. The findings could also guide future clinical trials, inform material selection, and help clinicians optimize infection control in endodontic procedures for better patient care.
Overall, the current review provides clear evidence that Biodentine has a strong efficacy in inhibiting the growth of E. faecalis. In addition, most of the studies supported that the antibacterial activity of Biodentine increases or stays nearly at the same level over time. Furthermore, Biodentine was superior to or, at least, as efficacious as MTA, MTA Angelus, GIC, RMGIC, DiaRoot BioAggregate, NeoPutty, iRoot FS, MTA Repair HP, MTA Biorep, Well-Root PT, Activa, NeoMTA 2, Calcimol LC, TotalFill, and IRM.
Considering the limitations of this systematic review, there is accumulating evidence of the antibacterial activity of Biodentine against E. faecalis in the context of endodontics. However, randomized clinical trials with well-designed and robust methodologies are required to provide information about its clinical behaviour. The findings were supported by studies with medium to high risk of bias (low quality). There is a demand for low-risk-of-bias studies to further evaluate the finding's reliability. Furthermore, it is highly suggested to develop standardized methods to evaluate the antibacterial efficacy of endodontic materials in in vitro investigations.
The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding authors.
HS: Methodology, Writing – review & editing, Writing – original draft, Conceptualization, Formal Analysis, Investigation, Project administration, Supervision. NS: Writing – original draft, Conceptualization, Formal Analysis, Investigation, Supervision, Writing – review & editing. SA: Writing – original draft, Writing – review & editing. MSA: Data curation, Writing – review & editing. AT: Methodology, Writing – review & editing, Formal Analysis.
The author(s) declare that no financial support was received for the research, authorship, and/or publication of this article.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
HS, Hasan Subhi; NS, Nashwah Subhi; SA, Salah Alhaidary; MSA, Mahmood S. Azeez; AT, Abedelmalek Tabnjh; ADT, agar diffusion test; CEM, calcium-enriched mixture; CFUs, colony forming units; DCT, direct contact test; E. faecalis, Enterococcus faecalis; ERRM, endosequence root repair material; GIC, glass ionomer cement; MeSH, medical subject headings; MIC, minimal inhibitory concentration; MTA, mineral trioxide aggregate; OD, optical density; PRISMA, preferred reporting items for systematic reviews and meta-analyses; RMGIC, resin-modified glass ionomer cement.
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Keywords: antibacterial, biodentine, Enterococcus faecalis, endodontic treatment, endodontic failure, systematic review
Citation: Subhi H, Subhi N, Alhaidary S, Azeez MS and Tabnjh AK (2025) Antibacterial activity of biodentine against Enterococcus faecalis: a systematic review. Front. Dent. Med 5:1498353. doi: 10.3389/fdmed.2024.1498353
Received: 18 September 2024; Accepted: 30 December 2024;
Published: 21 January 2025.
Edited by:
Carla Sipert, University of São Paulo, BrazilReviewed by:
Cristiane Cantiga-Silva, São Paulo State University (Unesp), BrazilCopyright: © 2025 Subhi, Subhi, Alhaidary, Azeez and Tabnjh. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Abedelmalek Kalefh Tabnjh, YWJlZGVsbWFsZWsua2FsZWZoLnRhYm5qaEBndS5zZQ==; Hasan Subhi, aHNuc3VhekBnbWFpbC5jb20=
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