Sage Journals: Discover world-class research

Abstract

Many types of endodontic root canal sealers have been employed for the purpose of filling voids and irregularities in root canals, as well as reducing/removing bacterial remnants/remains. Sealers are available in various formulations, and research work to find the most appropriate ones is still ongoing. Recently, many kinds of novel root canal sealers have been introduced under various commercial names. However, most sealers are known to exhibit different levels of cytotoxicity on tissues which would result in prolonged wound healing, inflammation, and bone resorption. Preferably, sealers need to have tolerable biological and physico-chemical properties along with biocompatibility. Additives promoting the biocompatibility and bioactivity of sealers are of major concern in clinical applications. The aim of this review was to compare, evaluate, and analyze comparatively the cytotoxic effects, biocompatibility, and antimicrobial properties of recently used root canal sealers. A comprehensive literature search was made to identify their properties involving biocompatibility and cytotoxicity. In general, the sealers reported in recent literature exhibited favorable biological features in comparison to conventional ones. They promoted better cell viability and biocompatibility. The incorporation of additives influences favorably the potential negative effects. However, it has been highlighted that there is a lack of well-designed long-term clinical applications, and more in vitro and in vivo research work would be helpful to confirm the sustainability of the sealers for further clinical practice.

Keywords

Cytotoxicity biocompatibility biomaterials endodontic root canal sealers physico-chemical properties

Highlights

Novel endodontic root canal sealers appeared in recent studies

A comprehensive literature search to identify the biological and physico-chemical properties, biocompatibility, cytotoxicity, antimicrobial properties related to various recent novel root canal sealers

Comparative evaluation with conventional endodontic root canal sealers

Need for well-designed long-term clinical appli-cations

Need for further in vitro and in vivo work to clarify the mechanism and for the confirmation of the sustainability of their utilization for clinical practice

Introduction

The objective of endodontic therapy is the successful treatment of root canal infection, cleaning, and shaping of the root canals, filling the root canal space, thus preventing the coronal and apical microorganism and liquid penetration.^1–5 Most of the root canals are filled with a proper sealer which is the main component of root canal obturation to build a liquid-tight seal.^6,7 Endodontic root canal sealers have been commonly employed for sealing of dentinal tubules to create a homogenous interface between the dentinal walls and the obturation material,^5,8 thus contributing to the obturation of canal space.^9,10 The main functions of sealers include filling the void and irregularities involved in the root canal, destroying the remaining bacteria left after cleaning, and shaping of the root canal by its germicidal action.^7,11

A diverse range of root canal sealers have been used, along with a solid or a semisolid filler. They are prepared in various forms such as epoxy resin, zinc oxide–eugenol, calcium hydroxide, silicone, bioceramic, glass ionomer-based sealers with different setting formations^6,8,11–13 (Figure 1). Although many formulations are available, research work to find the most appropriate ones is still carried out.¹⁴ Recently, many kinds of novel root canal sealers were introduced under various commercial names.^7,11,15–19 The inclusion of agents into dental products to achieve tissue-remineralization and antibacterial functions are considerable.²⁰ Additives improving the biocompatibility and bioactivity characteristics of sealers are of major concern in clinical applications.^12,13 These improving strategies are highly promising for outcomes of root canal treatment and can potentially prevent and control endodontic pathologies.²⁰

Figure 1.

Root canal sealers in endodontic practice.

Biological interaction is explained by cytotoxicity, cytocompatibility or biocompatibility, cell plasticity, differentiation potential, and bioactive properties.²¹ Cytotoxicity is defined as the toxic effects of materials on vital tissues.¹⁸ The definition of biocompatibility is that having compatible and harmless properties of a material to the vital tissues.²² Biocompatible materials have stable and advantageous host responses during the application and do not influence an immunological or toxic response when contact with the tissue or tissue fluids.^22,23 On the other hand, bioactive materials have a structure that can form a bond between the material and tissue.^18,24 The research concerning biological interaction is crucial in determining the clinical impact of the materials.^18,25,26

Most of the endodontic root canal sealers are known to have some toxic properties or might be exhibiting different levels of cytotoxicity on tissues, which would result in prolonged wound healing, inflammation, and bone resorption.^7,27 Preferably, root canal sealers need to have tolerable biological and physico-chemical properties along with biocompatibility⁶ (Figure 2).

Figure 2.

Cytotoxicity and biocompatibility of root canal sealers.

Due to the significant influence of sealers in endodontic applications, their physical, chemical, and biological features have been the subject matter of many reports in the literature.^{17,21,28–32} However, no extensive comparative report on the cytotoxicity and biocompatibility of the recently developed sealers has been reported. The aim of this investigation is to assess and analyze the cytotoxic effects and biocompatibility of various root canal sealers in a comparative manner.

Search strategy and eligibility

A comprehensive literature search has been done to identify the properties related to various recent root canal sealers. Electronic databases such as PubMed, Google Scholar, and Web of Science were scanned for eligible articles. In order to reach current studies, the time frame was limited to the last 5 years using “biocompatibility + root canal sealers,” “biocompatibility + endodontics,” “cytotoxicity + root canal sealers,” “cytotoxicity + endodontics.” The inclusion criteria for this review involved the original data available including original articles published in English at peer-reviewed indexed journals. The exclusion criteria were non-English studies, systematic studies, case reports or letters, and articles not involving data. The in vitro studies on the physical and biological features of root canal sealers were assessed, covering different properties involving biocompatibility, cytotoxicity, and physical properties.

Review of the recent studies on the cytotoxicity and biocompatibility of endodontic sealers

Based on the historical review of the endodontic sealers about biocompatibility and cytotoxicity characteristics, even though some conflicting evidence was found, low biocompatibility had been presented in zinc oxide eugenol (ZOE) sealers while superior property for silicone-based and tricalcium silicate-based sealers. Moderate biocompatibility was noted in glass ionomer, methacrylate, and salicylate-based. Better biocompatibility was reported in methyl methacrylate-tributyl borane resin compared to other resin-based sealers.^13,33 Mineral trioxide aggregate (MTA) was the primary bioceramic material introduced in endodontics highlighted by its high bioactivity and biocompatibility.^34,35

Cytotoxicity and biocompatibility of various recently utilized endodontic root canal sealers discussed in the present study are shown in Table 1.

Table 1.

Cytotoxicity and biocompatibility of various endodontic root canal sealers recently utilized.

Materials	Methodology	Major findings	Reference
Tubliseal AH Plus Sealapex EndoREZ	Evaluation of the effect of addition of antioxidant like pachymic acid L929 mouse fibroblast cells in vitro Cytotoxicity: MTT-assey	• Root canal sealers exhibit cytotoxicity to varying degrees • Pachymic acid significantly reduced sealer-induced cytotoxicity • Methacrylate resin–based sealer: severely cytotoxic • Calcium hydroxide–based sealers: highly biocompatible • Sealapex: the lowest cytotoxicity • Pachymic acid: a viable therapeutic agent to overcome potential adverse effects associated with root canal sealers	Arun et al.²⁷
Sealer Plus AH Plus Endofill SimpliSeal	L929 fibroblast cells in vitro Cell viability: MTT-assey Subcutaneous implants in vivo Histologic analysis	• Sealer Plus: promoted greater cell viability, more biocompatible	Cintra et al.¹⁴
GuttaFlow Bioseal GuttaFlow2 MTA Fillapex AH Plus	hPDLSCs in vitro Cell viability: MTT-assey Cell Attachment: SEM	• Sealers’s extracts cause dose and timedependent effects on hPDLSCs • GuttaFlow Bioseal: lower cytotoxicity, better cytocompatibility	Collado-González et al.³⁶
RealSeal (dual polymerization experimental sealer) Dibutyltin (D)/calcium (C) methacrylate incorporation	L929 mouse fibroblast cells in vitro Antimicrobial Assay: Enterococcus faecalis Cell viability	• Evaluation of physical properties, antimicrobial effect, biocompatibility of D/C methacrylate incorporated experimental sealers • Antimicrobial effect potentiated by metal methacrylates • D/C incorporation promoted antimicrobial effect • C incorporation (0.5, 1.2%): a good treatment option for antimicrobial activity, moderate cytotoxicity, adequate physical properties • D-sealers provided a high cytotoxicity	Rossato et al.⁴⁷
BioRoot RCS Endosequence BC AH Plus	hMSCs in vitro Cytotoxicity: Alamar Blue Assay Cellular Morphology: SEM	• AH plus provided a high cytotoxicity • 1:2 BR: cell proliferation significantly lower • 1:8, 1:32: tricalcium silicate sealers similar cellular proliferation	Alsubait et al.⁴⁶
BioRoot RCS SimpliSeal MTA-Fillapex sealer	NIH/3T3 cells in vitro Cell viability: modified staining sulforhodamine B assay	• BioRoot RCS: a positive biological behavior, rather cytocompatible. • SimpliSeal: a strong cytotoxic effect • MTA-Fillapex sealer: significant cytotoxicity, acting rather as a resin sealer than as an MTA-based material	Vouzara et al.¹²
AH Plus Pulp Canal Sealer MTA Fillapex BioRoot RCS	Human osteoblasts in vitro Cell viability: MTT-assey Living-cell-count Living/dead-staining Cytotoxicity: LDH-assay	• Unset AH Plus and zinc-oxide eugenol based sealers more cytotoxic • Higher cell viability: BioRoot RCS	Jung et al.³⁹
Sealer Plus BC MTA Fillapex AH Plus	L929 fibroblast cells in vitro Cell viability: Alamar Blue assey Subcutaneous implants in vivo Histologic analysis	• Sealer Plus BC is biocompatible th MTA Fillapex and AH Plus	Benetti et al.³⁵
EndoSeal MTA Wellroot ST AH Plus AD Seal	hPDLSCs in vitro Cell Viability and Proliferation: MTT-assey Cellular Morphology: SEM Inflammatory Response: Enzyme-Linked Immunosorbent Assay Osteogenic activity: Alkaline Phosphatase staining	• AH Plus: lowest cell viability • Calcium silicate-based sealers: more biocompatible, less cytotoxic	Lee et al.⁴⁰
EndoSequence BC Sealer BioRoot RCS Endoseal MTA AH Plus	hDPSCs in vitro Cell Viability and Proliferation: MTT-assey Cell Migration Assay Cellular Morphology: SEM Mineralization activity: Alizarin Red Staining Assay	• Epoxy resin–based sealer: lowest biological properties • Calcium silicate-based sealers: similar cell viability in each other, superior biological properties compared to resin-based	Seo et al.⁴¹
EndoSequence BC Sealer ProRoot ES Roth AH Plus	Osteoblast precursor cell line (IDG-SW3) in vitro Cell Viability: Luminescence assay Osteogenic activity: Alizarin Red Staining Assay Fluorescence microscopy of DMP-1 expression Real-time reverse transcription polymerase chain reaction	• EndoSequence BC Sealer and ProRoot ES: significantly more biocompatible, promoted osteoblastic differentiation, well tolerated by osteoclast precursor cells-in vitro • AH Plus and Roth sealers: no bioactivity • AH Plus Sealer: abolished osteoblastic differentiation	Giacomino et al.⁸
Bio-C Sealer TotalFill BC Sealer AH Plus	hPDLSCs in vitro Cell viability: MTT-assey Cell Migration Assey Cellular Morphology: SEM Cell Attachment and Surface Morphology: SEM Mineralization activity: Alizarin Red Staining Assay	• AH Plus: lowest cell viability • Bioseramic sealers: more biocompatible, less cytotoxic	López-García et al.⁴²
EndoSequence BC Sealer EndoSequence BC Sealer HiFlow	Human periodontal ligament fibroblasts in vitro Cell viability: Cell Counting Kit-8	• HiFlow: better performance on flow/viscosity and film thickness, especially under high temperatures, which were generated by the warm vertical compaction technique	Chen et al.⁴⁵
BioRoot RCS ProRoot ES MTA Fillapex AH Plus	hPDLSCs in vitro Cell viability: 2D PuraMatrix-encapsulated cells MTT-assey Multiplex Analysis of Cytokines and Chemokines In Vitro Root Model Experimental Procedure: 3D PuraMatrix-encapsulated cells	• Viability of PDLSCs • BioRoot RCS, ProRoot ES: did not induce proinflammatory cytokines • Promoted anti-inflammatory cytokine secretion by PDLSCs	Gaudin et al.³⁸
GuttaFlow Bioseal AH26	MDPC-23 odontoblast cell culture in vitro Cell viability: MTT and SRB assays Mineralization activity: Alizarin Red Staining Assay	• MDPC-23 odontoblast cell cultures • GuttaFlow Bioseal showed higher biocompatibility than AH26.	Ferreira et al.³⁷
Endoseal MTA Well-Root ST Nishika Canal Sealer BC AH Plus	hPDLSCs in vitro Cell viability: cell counting kit-8 Direct Contact Assay Inflammatory Gene Expression Osteogenic activity: Alkaline Phosphatase staining Angiogenesis Assay	• Nishika BC: prominent cytocompatibility, osteogenecity, and angiogenecity compared to other sealers in vitro.	Jo et al.⁴³
Polyurethane expandable endodontic sealer (PES)	L929 fibroblast cells in vitro Cell viability: MTS-assey Angiogenesis Assay	• Polyurethane expandable endodontic sealer (PES) • Promising biocompatibility and dentinal tubule adaptation and penetration	Saghiri et al.⁹

Cytotoxic and biocompatibility potential of endodontic sealers

Various sealers such as GuttaFlow2, MTA Fillapex, GuttaFlow Bioseal were evaluated by Collado-González et al.³⁶ concerning cytotoxic properties of some sealers on human periodontal ligament stem cells (hPDLSCs) in vitro. As a control for cell attachment and viability, AH Plus was used. Using eluates of sealers, cell viability assay was examined. hPDLSCs were seeded to the surfaces of materials to investigate the cell morphology and binding to the sealers. Analyses were carried out employing scanning electron microscopy (SEM), energy-dispersive X-ray (EDS), inductively coupled plasma mass spectroscopy (ICP-MS) techniques. Results exhibited a high proliferation level, cell spreading, and binding with GuttaFlow Bioseal disks. GuttaFlow2 and GuttaFlow Bioseal indicated less cytotoxic character. The extracts of sealers indicated time and dose-dependent influences on hPDLSCs. GuttaFlow Bioseal had better cytocompatibility, and additional in vitro and in vivo investigations with GuttaFlow Bioseal were proposed to confirm the suitability for clinical applications. Ferreira et al.³⁷ evaluated the cytotoxic response of GuttaFlow Bioseal and compared with epoxy resin sealer. Metabolic activity, cellular viability, the SRB and MTT assays were performed, and GuttaFlow Bioseal presented higher biocompatibility.

Vouzara et al.¹² investigated the cytotoxic feature of a bioceramic calcium silicate endodontic sealer (BioRoot RCS). They evaluated the influence of the sealer on cell viability and proliferation of cells cultured in comparison to calcium oxide and phosphate-containing epoxy (SimpliSeal) and a mineral trioxide aggregate filler containing salicylate (MTA-Fillapex) resin sealers. The tests were accomplished with NIH/3T3 cells grown as monolayer cultures by the application of the extracts of sealers to cells (24 h, 7 days). BioRoot RCS exhibited considerably lower cytotoxicity and was rather cytocompatible as compared to the others. SimpliSeal and MTA-Fillapex had significant cytotoxicity.

Cytotoxic properties of a calcium hydroxide-epoxy resin containing sealer (Sealer Plus) were found to be less cytotoxic compared to SimpliSeal, AH Plus, Endofill.¹⁴ L929 fibroblasts and MTT assay were utilized for the determination of the cytotoxic features of the sealer extracts with respect to time by Cintra et al.¹⁴ Tubes either empty (control) or with materials were employed for testing the rats’ subcutaneous tissues, and histologic analysis was performed after rats died (7, 30 days). Coherent with Cintra et al.,¹⁴ Benetti et al.³⁵ reached consistent results that Sealer Plus BC was biocompatible as compared to MTA Fillapex and AH Plus, and less cytotoxic when less-diluted extracts were applied.

Saghiri et al.⁹ evaluated the cytotoxicity and dimensional changes of a polyurethane expandable sealer (PES) developed recently. They used L929 fibroblasts and a cell viability assay (MTS) for the determination of the cytotoxicity of Sure-Seal Root, AH Plus, and PES dental sealers using extracted single-rooted human teeth. They utilized an advanced choroidal neovascularization model for evaluating the sealers on angiogenesis. SEM analysis was used for the measurement of the sealer penetration through the dentinal tubules. The choroidal neovascularization, MTS, and the penetration depth of PES were found considerably higher. PES exhibited promising results for dentinal tubule adaptation and penetration along with biocompatibility.

Gaudin et al.³⁸ studied cytotoxicity and influence of cytokine production of some calcium silicate-based endodontic sealers, including MTA Fillapex, ProRoot ES, and BioRoot RCS in different dimensions cell culture models. They assessed the influence of sealers on the production of cytokine and survival of hPDLSCs. AH Plus was the control material. The cells were cultured in either 2- or 3-dimensional medium (24 h) with the eluates of sealers. The toxicity of eluates was determined by the application of an in vitro root model. Cell viability and cytokine quantification were evaluated. BioRoot RCS exhibited good cell viability in 2-d culture conditions, whereas ProRoot ES did not indicate any effect. MTA Fillapex exhibited potent cytotoxicity even at the lowest dilutions. Encapsulation of cells by PuraMatrix lowered the cytotoxicity. In the 3-d model, MTA Fillapex, ProRoot ES, BioRoot RCS exhibited cytocompatibility patterns. Calcium silicate sealers showed unsimilar production of proinflammatory cytokine. In conclusion, ProRoot ES and BioRoot RCS did not induce proinflammatory cytokines but enhanced anti-inflammatory cytokine secretion.

The evaluation of the influence of antioxidant (pachymic acid) addition on the cytotoxic properties of different sealers in vitro, including ZOE (Tubliseal), epoxy resin (AH Plus), calcium hydroxide (Sealapex), and methacrylate resin (EndoREZ) based sealers showed that the pachymic acid addition led to a significant decrease of cytotoxicity except for the EndoREZ.²⁷ The experimental groups and subgroups by mixing the sealers were evaluated using mouse fibroblast cells (L929) with cell survival by methyl thiazole tetrazolium assay (24 h). All sealers exhibited cytotoxicity to varying degrees, while Sealapex was the lowest cytotoxic, following AH Plus, Tubliseal, and EndoREZ. Therefore, it was proposed as a viable therapeutic material to avoid the potential detrimental consequences of the sealers. Methacrylate resin containing sealer showed a severely cytotoxic effect, while calcium hydroxide-containing types were significantly biocompatible. Other research conducted on human osteoblasts using various sealers including AH Plus (epoxy resin-based), Pulp Canal Sealer (zinc-oxide eugenol containing), and MTA-Fillapex, BioRoot-RCS (calcium silicate-based) in an unset and set condition indicated that zinc-oxide eugenol containing sealer and unset AH Plus presented higher cytotoxicity.³⁹ In addition, it was concluded that BioRoot RCS influenced the cell metabolism and was slightly cytotoxic; however, compared with others, it had a better performance on cell viability.

Lee et al.⁴⁰ compared the effects of various calcium silicate-based sealers, including Wellroot ST, Nano-ceramic Sealer, EndoSeal MTA, and epoxy resin-based sealers such as AH Plus and AD Seal on different aspects such as inflammatory response, cell viability, and osteogenic potential on hPDLSCs in vitro. Furthermore, Seo et al.⁴¹ compared conventional resin-based to various calcium silicate-based sealers like BioRoot RCS, EndoSequence BC, Endoseal MTA about biocompatibility and mineralization activity on human dental pulp stem cells (hDPSCs). As a result of the mentioned studies, calcium silicate-based sealers appeared to be more biocompatible and less cytotoxic than epoxy resin-based sealers on different kinds of stem cells.

Biocompatibility of a calcium hydroxide-epoxy resin containing sealer (Sealer Plus) was found to be enhanced better cell viability and biocompatibility compared to SimpliSeal, AH Plus, and Endofill sealers.¹⁴ In addition, Sealer Plus BC was presented better biocompatibility as compared to MTA Fillapex and AH Plus.³⁵

Osteogenic potential of endodontic sealers

Giacomino et al.⁸ studied the osteogenic potential and biocompatibility of ProRoot ES and EndoSequence BC Sealer bioceramic sealers. They hypothesized that the sealers had superior features as compared with Roth and AH Plus types. In the method, murine osteoblast precursor cell line (IDG-SW3) was used at different concentrations (7 days). Cell survival was identified via ATP quantification. The osteogenic potential was analyzed by fluorescence microscopy (FM) through the use of osteogenesis markers (ALP, DMP-1, Phex). According to the results, both bioceramic sealers (EndoSequence BC Sealer, ProRoot ES) had excellent biocompatibility and promoted significantly osteoblastic differentiation, while EndoSequence BC Sealer indicated higher responses in vitro.

López-García et al.⁴² evaluated compatibility and mineralization potential of two premixed bioceramic root canal sealers, including Bio-C Sealer and TotalFill BC Sealer on hPDLSCs in comparison with epoxy-resin-based one. In the methodology, the researchers conducted cell viability assay, cell migration, cell morphology, cell attachment and surface morphology, and Alizarin Red assay for calcium mineralization. The results presented that TotalFill BC sealer and Bio-C sealer demonstrated better performance on biocompatibility compared to AH Plus.

The effect of biological and physico-chemical properties of endodontic sealers on biocompatibility, cytotoxicity, osteogenecity, and antimicrobial activity

Jo et al.⁴³ evaluated bioactive endodontic sealers (Well-Root ST, Endoseal MTA, Nishika Canal Sealer BG) with a resin-based control sealer (AH Plus) concerning chemical, physical, and biological properties, and the results were indicated that Nishika BG showed prominent compatibility, osteogenecity, and angiogenecity as compared to other root canal sealers in vitro. Almeida et al.⁴⁴ carried out a systematic review on the comparison of biological and physico-chemical features of calcium silicate-containing sealers with the regular ones in vitro. They compared many properties, including radiopacity, bond strength, solubility, setting- working time, flow, ion release, biocompatibility, antimicrobial activity, cytotoxic properties, and pH. The sealers had satisfactory biological and physico-chemical in vitro properties. Generally, the results were better than those of regular sealers. It was highlighted that calcium silicate-containing sealers presented suitable physico-chemical and biological features.

Chen et al.⁴⁵ investigated the influence of temperature and cytotoxicity on the physico-chemical features and the chemical composition of a calcium silicate, including EndoSequence BC Sealer HiFlow as compared to EndoSequence BC Sealer. The cell viability was evaluated using hPDLSCs. Several measurements such as the radiopacity, microhardness, setting time, film thickness, viscosity were performed. FTIR spectroscopy was utilized for the chemical analysis. Cell viability was shown to decrease significantly on day 3 for both materials (1:4). HiFlow was better performed for film thickness and flow/viscosity, especially at higher temperatures, influenced by the warm vertical compaction technique. On the other hand, Alsubait et al.⁴⁶ compared dose-dependent property on the cytotoxicity of Endosequence BC and BioRoot RCS sealers with using AH Plus as a control and indicated that both tricalcium silicate sealers led to similar cellular proliferation that were better than AH Plus.

According to the evaluation of biological and physical features of dual polymerization sealers containing metal methacrylates, calcium methacrylate sealers were proposed as a good option for antimicrobial activity.⁴⁷ The research work was conducted on the biocompatibility and the antimicrobial features of the dibutyltin or calcium methacrylate incorporated sealers. RealSeal was the control material. Sealers were assessed according to their radiopacity, film thickness, conversion degree, antimicrobial effect to E. faecalis, and cell viability. The film thickness of dibutyltin/calcium methacrylate incorporation in experimental sealers was higher than the other sealers, and the antimicrobial property was improved by the effect of metal methacrylate incorporation. Dibutylin methacrylate added sealers and RealSeal provided higher cytotoxicity, while calcium methacrylate provided moderate cytotoxicity.

The recent studies discussed above are mostly the results of in vitro findings. However, the behavior of materials used in biomedical applications would be different in the biological environment, and a considerable gap exists between the in vitro and in vivo analysis results. The influence of particles in biological medium needs to be further revealed, addressing the critical issues related to cytotoxic aspects of particles intended for use. The effects of various factors should be taken into account during particle-biomolecule interactions.⁴⁸

Conclusions

In general, the novel endodontic root canal sealers reported in the recent literature exhibited favorable biological features in comparison to conventional ones. They promoted better cell viability and were more biocompatible. For example, calcium silicate-containing sealers indicated optimal physico-chemical and biological characteristics in vitro and exhibited better properties than conventional sealers. They exhibited better performance on flow/viscosity and film thickness, especially at higher temperatures due to the warm vertical compaction techniques applied commonly. Silicate-based sealers enhanced anti-inflammatory cytokine secretion by PDLSCs. Investigation of the cytotoxicity of calcium silicate containing bioceramic sealer showed quite a positive biological behavior and was rather cytocompatible. Bioceramic sealers were found significantly more biocompatible and better tolerated by osteoclast precursor cells in vitro. They promoted osteoblastic differentiation that might be found in some sealers. A recently utilized polyurethane expandable sealer exhibited promising results in terms of dentinal tubule adaptation, penetration, and biocompatibility.

The incorporation of metallic methacrylates into endodontic sealers was proposed. Dibutyltin and calcium methacrylate incorporation promoted the antimicrobial effect of sealers. Dibutyltin caused a high, while calcium methacrylate resulted in moderate cytotoxicity. Calcium methacrylate sealers were proposed as a good option for antimicrobial activity. Additives used in conventional sealers influence favorably the potential negative effects related with root canal sealers and significantly reduce sealer-induced cytotoxicity. Calcium hydroxide–based sealers appear to be highly biocompatible, among the other zinc oxide eugenol, epoxy, and methacrylate resin sealers. It was highlighted that root canal sealers might exhibit varying levels of cytotoxic consequences. Methacrylate sealer appears to be severely cytotoxic. The extracts from sealers give rise to time and dose-dependent influences on hPDLSCs.

More in vitro and in vivo studies would be helpful to confirm the sustainability of the investigated sealers for clinical practice. It was also highlighted that there is a lack of well-designed long-term clinical applications. Further investigations would help to clarify the mechanisms contributing to the observed beneficial results. Additional protocols are needed in the evaluation of the chemical features of sealers for the interpretation of their biological behavior. Basic research protocol findings could further help to contribute to the successful sustainability of in vivo and clinical applications.

Footnotes

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

ORCID iDs

Olcay Özdemir

Turkan Kopac

References

Rover

Belladonna

Bortoluzzi

De-Deus

Silva

EJNL

Teixeira

CS.

Influence of access cavity design on root canal detection, instrumentation efficacy, and fracture resistance assessed in maxillary molars. J Endod 2017; 43: 1657–1662.

Yee

Newton

Patterson

Swartz

ML.

The effect of canal preparation on the formation and leakage characteristics of the apical dentin plug. J Endod 1984; 10: 308–317.

Siqueira Junior

Rôças

IDN

Marceliano-Alves

Pérez

Ricucci

Unprepared root canal surface areas: causes, clinical implications, and therapeutic strategies. Braz Oral Res 2018; 32: e65.

Azim

Aksel

Zhuang

Mashtare

Babu

Huang

GT.

Efficacy of 4 irrigation protocols in killing bacteria colonized in dentinal tubules examined by a novel confocal laser scanning microscope analysis. J Endod 2016; 42(6): 928–934.

Marciano

Bramante

Duarte

Delgado

Ordinola-Zapata

Garcia

RB.

Evaluation of single root canals filled using the lateral compaction, tagger’s hybrid, Microseal and Guttaflow techniques. Braz Dent J 2010; 21: 411–415.

Huang

F-M

Tai

K-W

Chou

M-Y

Chang

YC.

Cytotoxicity of resin-, zinc oxide-eugenol-, and calcium hydroxide-based root canal sealers on human periodontal ligament cells and permanent V79 cells. Int Endod J 2002; 35: 153–158.

Kaur

Shah

Logani

Mishra

Biotoxicity of commonly used root canal sealers: a meta-analysis. J Conserv Dent 2015; 18(2): 83–88.

Giacomino

Wealleans

Kuhn

Diogenes

Comparative biocompatibility and osteogenic potential of two bioceramic sealers. J Endod 2019; 45(1): 51–56.

Saghiri

Karamifar

Nath

Gutmann

Sheibani

A novel polyurethane expandable root canal sealer. J Endod 2021; 47(4): 612–620.

10.

Özdemir

Koçak

Hazar

Sağlam

Coşkun

Koçak

MM.

Dentinal tubule penetration of gutta-percha with syringe-mix resin sealer using different obturation techniques: a confocal laser scanning microscopy study. Aust Endod J. Epub ahead of print 13 July 2021. DOI: 10.1111/aej.12546.

11.

Al-Haddad

Che Ab Aziz

Bioceramic-based root canal sealers: a review. Int J Biomater 2016; 2016: 9753210.

12.

Vouzara

Dimosiari

Koulaouzidou

Economides

Cytotoxicity of a new calcium silicate endodontic sealer. J Endod 2018; 44(5): 849–852.

13.

Komabayashi

Colmenar

Cvach

Bhat

Primus

Imai

Comprehensive review of current endodontic sealers. Dent Mater J 2020; 39(5): 703–720.

14.

Cintra

LTA

Benetti

de Azevedo Queiroz

ÍO

, et al. Evaluation of the cytotoxicity and biocompatibility of new resin epoxy-based endodontic sealer containing calcium hydroxide. J Endod 2017; 43(12): 2088–2092.

15.

Uzunoglu-özyürek

Küçükkaya Eren

Karahan

Effect of root canal sealers on the fracture resistance of endodontically treated teeth: a systematic review of in vitro studies. Clin Oral Investig 2018; 22(7): 2475–2485.

16.

AlShwaimi

Bogari

Ajaj

Al-Shahrani

Almas

Majeed

In vitro antimicrobial effectiveness of root canal sealers against Enterococcus faecalis: a systematic review. J Endod 2016; 42: 1588–1597.

17.

Donnermeyer

Bürklein

Dammaschke

Schäfer

Endodontic sealers based on calcium silicates: a systematic review. Odontology 2019; 107(4): 421–436.

18.

Maru

Dixit

Patil

RSB

Parekh

Cytotoxicity and bioactivity of mineral trioxide aggregate and bioactive endodontic type cements: a systematic review. Int J Clin Pediatr Dent 2021; 14(1): 30–39.

19.

Marin-Bauza

Rached-Junior

Souza-Gabriel

Sousa-Neto

Miranda

Silva-Sousa

YT.

Physicochemical properties of methacrylate resin-based root canal sealers. J Endod 2010; 36: 1531–1536.

20.

Baras

Melo

MAS

Thumbigere-Math

, et al. Novel bioactive and therapeutic root canal sealers with antibacterial and remineralization properties. Materials 2020; 13(5): 1096.

21.

Sanz

Guerrero-Gironés

Pecci-Lloret

Melo

Biological interactions between calcium silicate-based endodontic biomaterials and periodontal ligament stem cells: a systematic review of in vitro studies. Int Endod J 2021; 54: 2025–2043.

22.

Washio

Morotomi

Yoshii

Kitamura

Bioactive glass-based endodontic sealer as a promising root canal filling material without semisolid core materials. Materials 2019; 12(23): 3967.

23.

Marin

Boschetto

Pezzotti

Biomaterials and biocompatibility: an historical overview. J Biomed Mater Res 2020; 108: 1617–1633.

24.

Vallittu

Boccaccini

Hupa

Watts

DC.

Bioactive dental materials-do they exist, and what does bioactivity mean?

Dent Mater 2018; 34(5): 693–694.

25.

Sanz

Rodríguez-Lozano

Lopez-Gines

Monleon

Llena

Forner

Dental stem cell signaling pathway activation in response to hydraulic calcium silicate-based endodontic cements: a systematic review of in vitro studies. Dent Mater 2021; 37: e256–e268.

26.

Liu

, et al. Cell migration and osteo/odontogenesis stimulation of iRoot FS as a potential apical barrier material in apexification. Int Endod J 2020; 53(4): 467–477.

27.

Arun

Sampath

Mahalaxmi

Rajkumar

A comparative evaluation of the effect of the addition of pachymic acid on the cytotoxicity of 4 different root canal sealers-an in vitro study. J Endod 2017; 43(1): 96–99.

28.

Silva

EJNL

Cardoso

Rodrigues

De-Deus

Fidalgo

TKDS.

Solubility of bioceramic- and epoxy resin-based root canal sealers: a systematic review and meta-analysis. Aust Endod J 2021; 47: 690–702.

29.

Sponchiado Junior

Vieira

WDA

Normando

AGC

, et al. Calcium silicate-based sealers do not reduce the risk and intensity of postoperative pain after root canal treatment when compared with epoxy resin-based sealers: a systematic review and meta-analysis. Eur J Dent 2021; 15(2): 347–359.

30.

Sanz

Rodríguez-Lozano

Llena

Sauro

Forner

Bioactivity of bioceramic materials used in the dentin-pulp complex therapy: a systematic review. Materials 2019; 12(7): 1015.

31.

Šimundić Munitić

Poklepović Peričić

Utrobičić

Bago

Puljak

. Antimicrobial efficacy of commercially available endodontic bioceramic root canal sealers: a systematic review. PLoS One 2019; 14(10): e0223575.

32.

Gandolfi

Parrilli

Fini

Prati

Dummer

PM.

3D micro-CT analysis of the interface voids associated with Thermafil root fillings used with AH plus or a flowable MTA sealer. Int Endod J 2013; 46(3): 253–263.

33.

Fonseca

Paula

Marto

, et al. Biocompatibility of root canal sealers: a systematic review of in vitro and in vivo studies. Materials 2019; 12(24): 4113.

34.

Pelliccioni

Vellani

Gatto

Gandolfi

Marchetti

Prati

Proroot mineral trioxide aggregate cement used as a retrograde filling without addition of water: an in vitro evaluation of its microleakage. J Endod 2007; 33(9): 1082–1085.

35.

Benetti

de Azevedo Queiroz

ÍO

Oliveira

PHC

, et al. Cytotoxicity and biocompatibility of a new bioceramic endodontic sealer containing calcium hydroxide. Braz Oral Res 2019; 33: e042.

36.

Collado-González

Tomás-Catalá

Oñate-Sánchez

Moraleda

Rodríguez-Lozano

FJ.

Cytotoxicity of GuttaFlow bioseal, GuttaFlow2, MTA Fillapex, and AH Plus on human periodontal ligament stem cells. J Endod 2017; 43: 816–822.

37.

Ferreira

Laranjo

Marto

, et al. GuttaFlow^® bioseal cytotoxicity assessment: in vitro study. Molecules 2020; 25: 4297.

38.

Gaudin

Tolar

Peters

OA.

Cytokine production and cytotoxicity of calcium silicate-based sealers in 2- and 3-dimensional cell culture models. J Endod 2020; 46(6): 818–826.

39.

Jung

Sielker

Hanisch

Libricht

Schäfer

Dammaschke

Cytotoxic effects of four different root canal sealers on human osteoblasts. PLoS One 2018; 13(3): e0194467.

40.

Lee

Kim

Lee

Kim

In vitro comparison of biocompatibility of calcium silicate-based root canal sealers. Materials 2019; 12(15): 2411.

41.

Seo

Lee

Kim

Song

Kim

SY.

Biocompatibility and mineralization activity of three calcium silicate-based root canal sealers compared to conventional resin-based sealer in human dental pulp stem cells. Materials 2019; 12(15): 2482.

42.

López-García

Pecci-Lloret

Guerrero-Gironés

, et al. Comparative cytocompatibility and mineralization potential of Bio-C Sealer and TotalFill BC Sealer. Materials 2019; 12(19): 3087.

43.

Kim

Lee

, et al. Physical properties and biofunctionalities of bioactive root canal sealers in vitro. Nanomater 2020; 10(9): 1750.

44.

Almeida

SLH

Moraes

Morgental

Pappen

. Are premixed calcium silicate-based endodontic sealers comparable to conventional materials? A systematic review of in vitro studies. J Endod 2017; 43(4): 527–535.

45.

Chen

Haapasalo

Mobuchon

Shen

Cytotoxicity and the effect of temperature on physical properties and chemical composition of a new calcium silicate-based root canal sealer. J Endod 2020; 46(4): 531–538.

46.

Alsubait

Al Ajlan

Mitwalli

, et al. Cytotoxicity of different concentrations of three root canal sealers on human mesenchymal stem cells. Biomolecules 2018; 8(3): 68.

47.

Rossato

TCA

Gallas

da Rosa

WLO

, et al. Experimental sealers containing metal methacrylates: physical and biological properties. J Endod 2017; 43: 1725–1729.

48.

Kopac

Protein corona, understanding the nanoparticle-protein interactions and future perspectives: a critical review. Int J Biol Macromol 2021; 169: 290–301.

Cytotoxicity and biocompatibility of root canal sealers: A review on recent studies

Abstract

Keywords

Highlights

Introduction

Search strategy and eligibility

Review of the recent studies on the cytotoxicity and biocompatibility of endodontic sealers

Cytotoxic and biocompatibility potential of endodontic sealers

Osteogenic potential of endodontic sealers

The effect of biological and physico-chemical properties of endodontic sealers on biocompatibility, cytotoxicity, osteogenecity, and antimicrobial activity

Conclusions

Footnotes

Declaration of conflicting interests

Funding

ORCID iDs

References