Increasing Use of Bioceramics in Endodontics: A Narrative Review

Abstract
Successful outcomes of root canal treatment, in addition to a multitude of factors, also depends on the prevention of reinfection of the root canal space. The ultimate goal of root canal treatment is prevention or healing of apical periodontitis. The use of biologically active materials to seal root canal systems has been extensively proposed in contemporary endodontics to realise this goal. There are several commercial formulations of bioceramics available based on minor variations in composition which could have potentially important changes in properties in the clinical situation. This narrative review serves to provide brief information on the different formulations of bioactive ceramics that are available to a dentist.

The term “bioceramics” may be applied to the category of biomaterials that are composed of ceramic as one of its constituents. These materials were developed to have biocompatibility with human tissue, and be widely used in repair and replacement of the organs in the musculoskeletal system. Based on the microstructure and minor compositions, one may broadly classify these materials into1: bioinert, bioactive and bioresorbable.

While bioinert materials do not demonstrate osteoconductive or osteoinductive properties, they allow growth of fibrous tissues around the material. Examples of this category are alumina and zirconia. Bioactivate materials, in contrast, have osteoinductive and osteoconductive properties. They are porous and develop an interfacial bond with the hard tissues. Hydroxyapatites, bioactive glasses and glass ceramics are examples of this class of bioceramics. Bioresorbable ceramics enhance the replacement resorption of the material by host tissues when the rate of resorption correlates with the rate of regeneration. Examples of this group of materials are tricalcium silicates and calcium phosphate. 2

There has been an increasing trend towards the application of bioceramics in medical and dental fields. In bone tissue engineering, they have been used as bone surrogates, bone implants and as a composition of artificial joints. They are also used in making artificial heart valves. In dentistry, they are widely used as compositions of implants and periodontal surgeries, i.e. for alveolar ridge augmentation. 3 Since 1993, the field of endodontics has seen a huge influx of this category of materials with a wide array of applications. The first endodontic use of this class of materials was in the form of Mineral Trioxide Aggregate (MTA), used for perforation repair and root end filling. 4-6 An extensive literature search on Medline revealed 1958 articles on MTA as on September 15, 2016. In general, it has been widely noted that MTA has excellent biocompatibility and sealing ability owing to its bioactive nature. This material is now considered the gold standard for direct pulp capping, perforation repair, root-end filling and apexification. 2 Nevertheless, MTA does have disadvantages including long setting time, low cohesive strength and poor handling properties. 8 The possibility of biocompatibility issues due to heavy metal leaching 9 and coronal discoloration 10,11 have also been reported.

From a chemical perspective, most bioactive materials used in endodontics are based on tricalcium and dicalcium silicate. 2,8 When these tri-and dicalcium silicates interact with water, calcium silicate hydrate (CSH) gel is formed, initially as a colloidal gel, which then hardens with time. The bioactivity has also been reported to be due to the release of calcium hydroxide (CH) during the hydration process. 12,13 Thus, this group of materials are also termed “calcium silicate based cement” or “hydraulic calcium silicate based cement”. 2,14 When calcium phosphate monobasic was added to the calcium silicates, a complex reaction ensues, resulting in the formation of CSH gel and CH. In addition, the calcium phosphate monobasic reacts with CH to form hydroxyapatite-like compounds or an apatite-like layer which co-precipitates with the CSH phase, thereby reinforcing the set cement. This property of “biomineralisation” helps improve the tissue attachment of these materials. 15,16 The purpose of this narrative review is to critically discuss the increasing use of bioceramic materials in endodontics with specific emphasis of the commercial variations from a clinical perspective.

Calcium Silicate Based Cements
ProRoot MTA (Dentsply Tulsa Dental, Tulsa, OK, USA):
ProRoot MTA is considered a prototype of bioceramics in endodontics. It was developed and first introduced in Loma Linda University, USA in 1993, and was patent registered in 1995. The white ProRoot MTA or tooth-colored ProRoot MTA was later developed in 2002. ProRoot MTA is one of the most widely researched endodontic materials, including short- and long-term treatment outcome studies. 5-7,17-22 ProRoot MTA has been shown to demonstrate the least cytotoxicity and leakage compared with other materials, and has been proven to induce osteogenesis and cementogenesis. 23,24 The compressive strength of MTA was about 40 MPa at 24 hours and 67.3 MPa at three weeks. 19 Clinical applications of ProRoot MTA in endodontics included pulp protection in vital pulp therapy, perforation and resorption repair, apexification, revascularization and root end filling during apicectomy. 25

MTA Angelus (Angelus, Londrina, Brazil):
This commercial formulation of MTA composes of 80% Portland cement and 20% Bismuth oxide. Calcium sulfate was removed from the liquid portion in order to accelerate the setting time, which is reduced down to 14 minutes. 26 MTA Angelus exhibits excellent biocompatibility 27 and sealing ability 28, and increased bone formation. 29 However, an investigation by Camilleri 30 revealed that due to an incomplete sintering process leading to its variability in mineralogy, MTA Angelus contained smaller amount of tricalcium silicate, but more of calcium, aluminum and silicon oxides in the un-hydrated powder compared to Biodentine. The greater amount of CH produced as a by-product of the reaction due to hydration of calcium oxide leads to more porous and less dense microstructure.

MTA Plus and NeoMTA Plus (compounded by Avalon Biomed Inc, Bradenton, FL, USA for Prevest Denpro, Jammu, India):
With an increasing body of evidence demonstrating the biomineralisation properties of tricalcium silicates, the application of MTA logically extended to being used as root canal sealers. 2 ProRoot MTA and MTA Angelus were not intended to be applied as root canal sealers. A new group of cost-effective materials (MTA Plus and NeoMTA Plus) were introduced into the market for all conceivable applications of bioactive ceramic materials (vital pulp therapy, apexification, root end filling, perforation repair, resorption management and root canal sealer. While the basic composition of MTA Plus is similar to that of the original MTA, there are two main differences: the powder of MTA Plus is finer and it is recommended that the MTA powder be mixed with a proprietary water-based gel when the material is to be used as a root canal sealer.) 30,31 This gel contains film forming polymers and accelerators but no salts. Currently, three variants of this material are available: Gray MTA Plus, MTA Plus and NeoMTA Plus.

Gray MTA Plus/ MTA Plus is a powder and liquid/ gel system. The powder consists of fine inorganic substance similar to that of ProRoot MTA. Liquid or gel may be used for cavity liner/base, pulp capping, pulpotomy, root apexification, resorption/perforation repair or root-end filling material. The water-based gel (with water soluble thickening agents and polymer) imparts washout resistance and faster setting, which the liquid does not. 32,33 The manufacturer recommends mixing the powder with gel into a syrupy, stringy consistency when used as a root canal sealer during obturation.
NeoMTA Plus is a powder-gel system. The powder components are an extremely fine powder primarily tricalcium and dicalcium silicate, quite similar to that of white ProRoot MTA, but contains no bismuth oxide in order to prevent tooth staining. 34 Tantalum oxide is used as the radiopacifier. The manufacturer claims that this material achieves washout resistance in less than three minutes (MTA Plus is about five minutes), thus allowing continuation of the restorative procedure. Also it has a 20-minute working time and a 50-minute setting time when mixing to a putty consistency. Thus, the setting time of both MTA Plus and NeoMTA Plus are depending on the consistency of the mixed material.
The setting time of MTA Plus was found retarded when in contact with fluids; about 128 minutes in dry condition and about 1,052 minutes in contact with physiological solution. 32 While the hydration of the core material was not affected by contact with the different solutions but the periphery exhibited microcracking, leaching of calcium hydroxide, partial decalcification of calcium silicate hydrate, and interaction with a physiological solution resulted in inhibition of hydration. 32,33 The compressive strength was significantly lower when MTA Plus mixed with liquid was exposed to the biological fluid compared with saline. However the material mixed with gel was not affected in this condition. 35

Endocem (Maruchi, Wonju, Korea):
EndoCem is a group of products available in four different forms:

Endocem MTA: this material contains a fine size of pozzolan. Pozzolan is a material that contains silica or silicate (sometimes with aluminum) with little or no cementitious value themselves, but in the presence of water, react chemically with calcium hydroxide to form calcium silicate, with good cementing properties. The major chemical constituents and applications are similar to ProRoot MTA. 36 The manufacturer claims that the pozzolanic reaction blocks the dentinal tubules, thereby preventing discoloration of the tooth. Setting time is about two to four minutes.
Endocem Zr: contains zirconium as the most abundant element. The use is similar to that of white MTA but application of direct occlusal force should be avoided because the material exhibits less tensile strength than the conventional MTA. It has also been suggested that this material be used as a liner rather than a base in vital pulp therapy. Setting time is about four minutes.
Endoseal: a root canal sealer without resin as its component, which has MTA as its main ingredient.
Endodseal MTA: a premixed root canal sealer based on pozzolan in a syringe, which main compositions of calcium silicates, calcium aluminates, calcium aluminoferrite, calcium sulfates, radiopacifier, and thickening agent. The setting time reported by the manufacturer is about 12.31 minutes.
Calcium ions release from water-immersed set Endocem MTA and Endocem Zr were noted to be significantly less compared with white MTA, and when immersed in phosphate-buffered saline for 14 days, they also produced apatite-like crystalline precipitates like ProRoot MTA, but with less calcium/phosphate ratio. 36 Endocem Zr was also noted to have transient cytotoxicity initially, and the levels of vascular endothelial growth factor and angiogenin were also significantly lower than that of ProRoot MTA. 37 However, a randomized controlled study recently revealed that Endocem exhibited similar success with ProRoot MTA as a direct pulp capping material, evaluated clinically and radiographically over one year after the treatment. 22

Retro MTA and Ortho MTA (BioMTA, Seoul, Korea):
The main composition of Ortho MTA is similar to ProRoot MTA, i.e. tricalcium silicate, dicalcium silicate, tricalcium aluminate, tetracalcium aluminoferrite, calcium oxide and bismuth oxide, and is suggested to be used as root-end filling material after apicectomy. Retro MTA is a powder consisting fine hydrophilic particles of calcium carbonate, silicon dioxide, aluminum oxide, and hydraulic calcium zirconium complex as a radiopacifier. Retro MTA is more granular in nature and sets faster than Ortho MTA. This faster setting finds advantage when used as a pulp capping material. 36 Studies of both materials are limited and most data is manufacturer-released information. One investigation compared the cytotoxicity of ProRoot MTA, Ortho MTA and glass ionomer cement and reported that ProRoot MTA and glass ionomer cement had better biocompatibility compared to Ortho MTA, while Retro MTA has similar biocompatibility and angiogenic effects on human pulp cells compared to ProRoot MTA. 37,38 The setting time of Retro MTA and Ortho MTA are about 1.5-2.5 minutes and three minutes respectively.

Biodentine (Septodont, Saint Maur des Fosses, France):
Biodentine is a calcium silicate-based cement that has tricalcium silicate as its main constituent, but contains Zirconia as radiopacifier. The addition of calcium carbonate in the powder and calcium chloride in the liquid helps accelerate the setting time. The hydro-soluble polymer helps disseminate the particles in the powder while mixing and reduces the proportion of water in the reaction. Results from this mixture makes the setting time of Biodentine as fast as 10 to 12 minutes as claimed by the manufacturer and 6.5 to 45 minutes as reported by others. 39-41 The initial compressive strength of Biodentine has been reported to be significantly higher than MTA but the compressive strength of MTA increases significantly with time. 41

In contact with phosphate in the body fluid, Biodentine forms hydroxyapatite precipitates, which penetrates into the dentinal tubules. 42 The performance of this material is easily affected by the powder-liquid ratio. The material has low viscosity similar to zinc phosphate cement 43 initially after mixing, and the viscosity increases rapidly with time. Thus, the operator would have to adjust the mixing time until the consistency is suitable for the required work, i.e. the material would need a better flow for pulp capping but higher viscosity while using as a root-end filling material. Clinical applications of Biodentine in endodontics are quite similar to those of ProRoot MTA. In the restorative field, Biodentine has also been suggested as a temporary restoration and a dentin replacement material. However, as the complete setting time takes up to two weeks prior to permanent restoration with composite resin, its clinical applicability for this specific purpose has not achieved wide spread recognition. 44

Calcium Phosphate Silicate Cement
BioAggregate (Innovative Bioceramix Inc., Vancouver, Canada):
BioAggregate is a biocompatible nano-particulate pure white powder composed of bioceramic nano-particles (below 2 microns). The major constituents are tricalcium silicate and dicalcium silicate, but it is an aluminate-free bioceramic material. Instead of bismuth oxide, tantalum pentoxide, which is more chemically inert, is used as radiopacifying agent. This could be one reason for the reported biocompatibility and reduced possibility of tooth discoloration. 45

The biocompatibility of BioAggregate has been reported to be comparable to MTA and Biodentine but the compressive strength has been shown to be significantly lower. 46 The compressive strength of BioAggregate is low (approximately 16 MPa), and the setting time is within four hours in the manufacturer recommended optimal powder-liquid ratio (1 gram to 0.38 mL). 41,46 Hence, there appears to be no strong evidence to use BioAggregate as an alternative to the MTA formulations. 8

EndoSequence Root Repair Material (ERRM) or Bioceramic Root Repair Material (BC RRM) (Brasseler USA, Savannah, GA, USA):
EndoSequence Root Repair Material (ERRM) or EndoSequence Bioceramic Root Repair Material (BC RRM) is a recent premixed bioceramic material in the calcium phosphate silicate cement group. These materials were developed for permanent root canal repair applications with improved handling properties and shorter setting times. This material contains calcium silicates, zirconium oxide, tantalum oxide and calcium monobasic. The manufacturer claims that the material is aluminium-free, resistant to wash out, and does not shrink during setting.

The material is available in three specifically formulated consistencies. Their trade names are different according to the countries they are marketed [iRoot in Canada (Innovative BioCeramix, Vancouver, Canada) and TotalFill (FKG Dentaire SA, La Chaux-de-Fonds, Switzerland) in the countries out of North America].

BC RRM-Paste Syringeable (iRoot BP or TotalFill Paste): the material can be injected into areas that are difficult to access such as internal resorption.
BC RRM-Putty (iRoot BP Plus or TotalFill Putty): is a white hydraulic putty consistency material. The material can be scooped out from the container, molded and shaped so as to be easily compressed into the resorptive or perforated areas or the apical canal during root end filling. The setting time of the BC RRM-Paste and Putty is about
two hours.
BC RRM-Fast Set Putty (iRoot FS or TotalFill Fast Set-Putty): contains the same characteristics as the BC RRM-Paste and BC RRM-Putty, but the manufacturer claims a faster setting time. The setting time is about 20 minutes, dependent upon the moisture in the dentin. The manufacturer claims that no additional moisture is required to initiate the hydration process of this cement. It is recommended to apply a thin layer of self cure or dual cure glass ionomer cement over the material for single-visit perforation repair of small perforations prior to fabrication of a resin composite as a final restoration. For the two-visit perforation repair of larger defects, an application of a moist cotton pellet over the material prior to temporization is suggested by the manufacturer.

One recent study reported that the complete setting time of the Fast Set consistency could be up to one-hour, and up to seven days for the original Putty form. 47 When compared BC RRM with ProRoot MTA, both materials demonstrated comparable but negligible cytotoxicity and compressive strength. 47-49 However, BC RRM could maintain its compressive strength when exposed to biological fluid, in contrast to ProRoot MTA. 42 The Fast Set Putty formula also exhibited the best cell adhesion compared to the original putty form and ProRoot MTA due to it finer microstructure. 47 Chen and coworkers assessed the treatment outcome of root-end surgery after six months using two root-end materials, ProRoot MTA and BC RRM in beagle dogs, and reported that although both materials possess similar biocompatibility and assumed sealing ability, preferred histological outcomes were observed with BC RRM. 49 The authors reported that a greater area of the resected dentin and the material surface was covered by mineralized (cementum-like) tissue and underneath dense fibrous (periodontal ligament-like) tissue and bone when using BC RRM.

Tech Biosealer (Isasan SRL, Rovellor Porro, Italy):
This group of materials is marketed in four variations within the endodontic realm. Tech Biosealer Endo, Tech Biosealer Root end, Tech Biosealer Apex and Tech Biosealer capping. The body of research on these materials is scarce and the exact differences between these materials is unclear. This material is based on phyllosilicate [montmorillonite] in addition to tricalcium silicate, calcium sulfate, calcium chlorite, bismuth trioxide and sodium fluoride in the powder. One report demonstrated that the dislocation resistance of Tech Biosealer Endo did not significantly improve with time after the root canals were irrigated with different irrigation protocols. 50 This calls for further research on the bioactivity of this material.

Bioceramic Sealers and Hybrid Bioceramic Sealers in Endodontics
Bioceramic sealers are sealers those contain calcium silicate and/or calcium phosphate as their main compositions, i.e., Endosequence BC Sealer while Hybrid bioceramic sealers are resin-based root canal sealers or other root canal sealers those contain some bioceramic components, i.e., MTA Fillapex.

Endosequence BC Sealer(iRoot SP Sealer or TotalFill BC Sealer):
This premixed ready-to-use injectable white hydraulic cement paste is a pure bioceramic root canal sealer composed of tricalcium silicate, dicalcium silicate, colloidal silica, calicium phosphate monobasic, calcium hydroxide and thickening agent. Zirconium oxide is used as the radiopacifier, and the material is claimed to be aluminum-free, non-soluble and does not shrink during setting. The setting time of the sealer is dependent upon the presence of moisture in the dentinal tubules. According to the manufacturer, the sealer usually sets within four hours, but if the dentin is very dry, the setting time could take up to 10 hours. However, one study demonstrated that the setting time and micro-hardness of the sealer could be affected by excessive wet environment, i.e. the initial and final setting time could take up to 72 and 240 hours under 100% relative humidity, and the setting time tended to increase, while the micro-hardness tended to decrease when the higher amount of water was incorporated into the sealer. 51 Atleast one study reported that this material did not undergo complete setting even after 48 hours. 50 The pH of the sealer during setting could be higher than 12, and this could attribute to its antibacterial effect. 36 Haapasalo et al. demonstrated that fresh iRoot SP could kill all bacteria within two minutes of contact and continued to be effective until three and seven days after mixing. 52

MTA Fillapex:
MTA Fillapex is a two-paste system of salicylate resin based root canal sealer with MTA component in an automix syringe or tubes. Paste A is composed of salicylate resin, bismuth trioxide as radiopacifier and fumed silica as filler. Paste B contains a base resin as plasticizer, MTA (13.2%), titanium dioxide as filler and fumed silica. 31 The working time is about 30 minutes and the complete setting time is approximately two to 4.5 hours. 53 The material has been reported to show lesser flow, lower solubility and less water absorption than AH Plus, and it exhibited good physical properties to be used as endodontic sealer. Nevertheless, evidence on this material is highly variable. Initial cytotoxicity during setting was observed but the material presented capability to facilitate nucleation sites for apatite crystal formation in human osteoblast-like cell culture. 54 However, there appears to be no consensus on inclusion of this material as a bioceramic considering the minimal amount of MTA present in this formulation.

Increasing Use Of Bioceramic Sealers For Root Canal Obturation
Gutta-percha in combination with various types of root canal sealers has been the dominant root canal filling since mid-nineteenth century. However, with an increasing knowledge of root canal anatomy as well as the simplified matched cone obturation techniques, one relies on the sealer for providing a suitable seal which is oftentimes considered elusive. From a scientific standpoint, all root filling materials leak. 55 However, from a clinical standpoint. The root filling should be able to prevent leakage (coronal and apical) and entomb surviving microbiota. 56 In addition, the foundational requirements for root canal sealers, as laid down by Grossman hold true for the modern sealers as well: easy handling; dimensional stability, being impervious to moisture, antimicrobial activity, radiopaque, not cause tooth discoloration, biocompatible, and easily removed if necessary. 57

Recently, nano-particle bioceramic impregnated and coated gutta-percha points (Endosequence BC Gutta-Percha) have been developed to be used with Endosequence BC sealer under a “hydraulic condensation technique”. Advantages of this technique are: The remaining moisture in the canal and the natural moisture in the dentine enhances setting of the cement as the bioceramic sealer is highly hydrophilic; high pH above 12 of the sealer prior to setting gives rise to its antimicrobial properties; the sealer does not shrink but slightly expands, and it is insoluble in the presence of tissue fluids, thus allowing more amount of the sealer to be coated over the gutta-percha.; bonding between the bioceramic particles in the sealer and the nano-particles of bioceramic impregnated gutta-percha.; when using the BC Gutta Percha according the canal preparation size and shape, the matching cone acts like a root canal plugger, pushes the bioceramic sealer into the root canal irregularities with the hydraulic pressure. 58

Calcium silicate materials are commonly recommended by the manufacturer to be used as an obturation material itself or in a single-cone technique. Endosequence BC Sealer is also recommended to be used with BC Gutta Percha for optimal bond strength. DeLong and co-workers found that the continuous wave technique decreased the push-out bond strengths of EndoSequence BC Sealer compared to when the material was used with its matching BC point under single-cone technique. 58 This effect was the same for MTA Plus in the afore-mentioned work. The authors attributed that the sealers were possibly affected by the heat from the continuous wave technique. However, the push-out bond strength of the BC sealer with other types of gutta percha were found to be favorable and higher than that of AH Plus under the thermoplasticized technique. 59,60

A recent study evaluating the dentinal tubule penetration of different bioceramic sealers also revealed no difference between the continuous wave and the single-cone technique for BC Sealer, QuickSet and NeoMTA Plus at 1 and 5 mm from the apex. The depth of the penetration of these bioceramic sealers has been reported to be about 2 millimetres. 61 In contrast, the hybrid bioceramic sealer, MTA FillApex showed significantly less sealer penetration 1 mm from the apex when used with the single-cone compared with continuous wave technique. Further studies are required to evaluate the suitable technique for the best clinical performance of these new materials.

Impact Of Environmental Parameters On Bioceramic Materials
While the bioactivity of this group of materials is an intended clinical advantage, the dentin status following root canal disinfection as well the pH of the periradicular tissues may influence the hydration characteristics and thereby, the biomineralisation. 32

When MTA comes in contact with phosphate-containing fluids, calcium deficient carbonated apatites form via an amorphous calcium phosphate phase. The apatite thus formed deposits on the collagen fibrils. This process then initiates the formation of tag-like structures at the interface of MTA and dentin. While this process is termed “alkaline etching” and is essentially a form of hypermineralisation, this also appears to enhance the dislocation resistance of MTA from dentin. However, the long term effects of such a process are unknown. Nevertheless, studies on the dislocation resistance of bioceramics offer immense information on the hydration characteristics of these materials under different clinical conditions. 50

Discoloration of tooth structure following placement of MTA has been reported. This is especially important in cases where MTA is used a coronal barrier following regenerative endodontic procedures. 62 It was identified that the discoloration was due to the bismuth oxide component, which on exposure to light, undergoes oxidation and dissociates into metallic bismuth which has a dark color. Similarly, exposure to irrigating solutions such as sodium hypochlorite results in oxidation of the bismite component of MTA resulting in discoloration. 45,63 Characterization of MTA following exposure to sodium hypochlorite revealed a lack of Portlandite phase which implies some interference in the hydration mechanism of the cement. 45

However, such discoloration has not been reported to occur with other tricalcium silicates such as Endosequence or Biodentine. 11 This could be owing to the fact that these materials contain zirconium oxide or tantalum oxide instead of bismuth oxide. Bismuth oxide appears to play an important role in the hydration of tricalcium silicates and hence any negative impact on this component could interfere negatively with the setting and bioactivity of these materials. 13

For needle like nano apatite to form, the ideal pH should be greater than nine. Environmental variables such as acidic and alkaline pH influences this process thereby influencing the hydration mechanics of this material, interfering with the physicomechanical properties. One important influencing variable is remnant root canal irrigants on the dentinal wall. 50 A recent report suggested that sodium hypochlorite brought about a significant reduction in the compressive strength of White ProRoot MTA and MTA Angelus, while EDTA brought about significant reduction in the compressive strength of all the tricalcium silicates tested (White ProRoot MTA, MTA Angelus, NeoMTA Plus and Biodentine). 64

As mentioned earlier, this detrimental effect by sodium hypochlorite could be the result of the nature of radiopacifier in these materials. whereas EDTA, being a chelator is known to interfere with the formation of CSH gel resulting in reduced strength of all tricalcium silicates immaterial of the nature of the composition. 64,65 Hence it appears that a final rinse of NaOCl as well as EDTA could negatively influence the physicomechanical properties and biomineralisation potential of bioceramics. Hence extreme caution should be exercised in the clinical situation to thoroughly flush out remnants of chemically active irrigants. 66 The authors of this paper suggest that a the root canals be thoroughly irrigated with saline or distilled water in conjunction with activation methods such as passive ultrasonic irrigation prior to clinic use of bioceramic materials.

Conclusions
Although there has been increasing use of the bioceramic products, i.e. cements and sealers, in endodontics since the introduction of MTA and evident proof of its clinical outcomes, further studies are still required in the area of root canal sealer. There is, to date, still lack of outcome studies and publications are still limited and controversial due to variations in methodology.

It is important for clinicians to understand that in the world of continuous innovation, successful outcome of root canal treatment can be achieved not just be different materials, but is primarily driven by adequate removal of micro-organisms from the canal system, prevention of recolonization and entombment of residual species, and creating a satisfactory coronal restoration. However, considering the biological advantages of bioceramic (tricalcium silicate based) materials, their use in multiple paradigms of endodontic therapy appears to be the future. OH

Oral Health welcomes this original article.

Disclosure: The authors declare no conflict of interest

References
1. Hench L. Bioceramics. J Am Ceram Soc. 1998;81:1705-28.
2. Niu LN, Jiao K, Wang TD, Zhang W, Camilleri J, Bergeron BE, Feng HL, Mao J, Chen JH, Pashley DH, Tay FR. A review of the bioactivity of hydraulic calcium silicate cements. J Dent 2014: 42:517-533.
3. Haapasalo M, Parhar M, Huang X, Wei X, Lin J, Shen Y. Clinical use of bioceramic materials Endod Topics. 2015;32:97-117.
4. Lee SJ, Monsef M, Torabinejad M. Sealing ability of a mineral trioxide aggregate for repair of lateral root perforations. J Endod 1993;19:541-4.
5. Torabinejad M, Watson TF, Pitt Ford TR. Sealing ability of a mineral trioxide aggregare when used as a root end filling material. J Endod 1993; 19:591-5
6. Torabinejad M, Higa RK, McKendry DJ, Pitt Ford TR. Dye leakage of four root end filling materials: effects of blood contamination. J Endod 1994;20:159–163.
7. Torabinejad M, Hong CU, Pitt Ford TR, Kettering JD. Cytotoxicity of four root end filling materials. J Endod. 1995;21:489–492.
8. Dawood AE, Parashos P, Wong RH, Reynolds EC, Manton DJ. Calcium silicate-based cements: composition, properties, and clinical applications. J Investig Clin Dent 2015 In Press. doi: 10.1111/jicd.12195
9. Kum KY, Zhu Q, Safavi K, Gu Y, Bae KS, Chang SW.Analysis of six heavy metals in Ortho mineral trioxide aggregate and ProRoot mineral trioxide aggregate by inductively coupled plasma-optical emission spectrometry. Aust Endod J 2013; 39:126-130
10. Bortoluzzi EA, Araújo GS, Guerreiro Tanomaru JM, Tanomaru-Filho M. Marginal gingiva discoloration by gray MTA: a case report. J Endod 2007, 33:325-7
11. Marconyak LJ Jr, Kirkpatrick TC, Roberts HW, Roberts MD, Aparicio A, Himel VT, Sabey KA. A Comparison of Coronal Tooth Discoloration Elicited by Various Endodontic Reparative Materials. J Endod 2016;42:470-3
12. Marciano MA, Duarte MA, Camilleri J. Calcium silicate-based sealers: Assessment of physicochemical properties, porosity and hydration. Dent Mater 2016;32: e30-40
13. Camilleri J. Characterization and hydration kinetics of tricalcium silicate cement for use as a dental biomaterial. Dent Mater 2011; 27:836-44
14. Darwell BW, Wu RC. “MTA”-an Hydraulic Silicate Cement: review update and setting reaction. Dent Mater 2011; 27:407-22
15. Dreger LA, Felippe WT, Reyes-Carmona JF, Felippe GS, Bortoluzzi EA, Felippe MC. Mineral trioxide aggregate and Portland cement promote biomineralization in vivo. J Endod 2012;38:324-9.
16. Reyes-Carmona JF, Felippe MS, Felippe WT. The biomineralization ability of mineral trioxide aggregate and Portland cement on dentin enhances the push-out strength. J Endod 2010; 38:286-91
17. Torabinejad M, Hong CU, Lee SJ, Monsef M, Pitt Ford TR. Investigation of mineral trioxide aggregate for root-end filling in dogs. J Endod. 1995;21:603–608.
18. Koh ET, Torabinejad M, Pitt Ford TR, Brady K, McDonald F. Mineral trioxide aggregate stimulates a biological response in human osteoblasts. J Biomed Mater Res. 1997;37:432–439.
19. Torabinejad M, Hong CU, McDonald F, Pitt Ford TR. Physical and chemical properties of a new root-end filling material. J Endod. 1995;21:349–353.
20. Schembri Wismayer P, Lung CY, Rappa F, Cappello F, Camilleri J. Assessment of the interaction of Portland cement-based materials with blood and tissue fluids using an animal model. Sci Rep 2016; 6:34547
21. Kang CM, Sun Y, Song JS, Pang NS, Roh BD, Lee CY, Shin Y. A randomized controlled trial of various MTA materials for partial pulpotomy in permanent teeth. J Dent 2016; S0300-5712(16)30142-7
22. Jang Y, Song M, Yoo IS, Song Y, Roh BD, Kim E.A Randomized Controlled Study of the Use of ProRoot Mineral Trioxide Aggregate and Endocem as Direct Pulp Capping Materials: 3-month versus 1-year Outcomes. J Endod 2015;41:1201-6
23. Shen Y, Peng B, Yang Y, Ma J, Happasalo M. What do different tests tell about the mechanical and biological properties of bioceramic materials? Endod Topics. 2015;32:47-85.
24. Koh ET, Torabinejad M, Pitt Ford TR, Brady K, McDonald F. Mineral trioxide aggregate stimulates a biological response in human osteoblasts. J Biomed Mater Res. 1997;37:432–439.
25. Tawil PZ, Duggan DJ, Galicia JC. Mineral trioxide aggregate (MTA): its history, composition, and clinical applications. Compend Contin Educ Dent 2015;36:247-52
26. Santos AD, Araujo EB, Yukimitu K, Barbosa JC, Moraes JC. Setting time and thermal expansion of two endodontic cements. Oral Surg Oral Med Orl Pathol Oral Radiol Endod. 2008;106:e77-9.
27. Poggio C, Ceci M, Beltrami R, Dagna A, Colombo M, Chiesa M. Biocompatibility of new pulp capping cement. Ann Stomatol (Roma). 2014;5:69-76.
28. Lolayekar N, Bhat SS, Hegde S. Sealing ability of ProRoot MTA and MTA-Angelus simulating a one-step apical barrier technique-an in vitro study. J Clin Pediatr Dent. 2009;33:305-10.
29. Gomes-Filho JE, de Moraes Costa MM, Cintra LT, Duarte PC, Takamiya AS, Lodi CS, et al. Evaluation of rat alveolar bone response to Angelus MTA or experimental light-cured mineral trioxide aggregate using fluorochromes. J Endod. 2011;37:250-4.
30. Camilleri J, Sorrentino F, Damidot D. Investigation of the hydration and bioactivity of radiopacified tricalcium silicate cement, Biodentine and MTA Angelus. Dent Mater. 2013;29:580-93.
31. Neelakantan P, Grotra D, Sharma S. Retreatability of 2 mineral trioxide aggregate-based root canal sealers: a cone-beam computed tomography analysis. J Endod 2013; 39:893-6.
32. Camilleri J, Formosa L, Damidot D. The setting characteristics of MTA Plus in different environmental conditions. Int Endod J. 2013;46:831-40.
33. Formosa LM, Mallia B, Camilleri J. Mineral trioxide aggregate with anti-washout gel–properties and microstructure. Dent Mater 2013;29:294-306.
34. Camilleri J. Staining Potential of Neo MTA Plus, MTA Plus, and Biodentine Used for Pulpotomy Procedures. J Endod. 2015;41:1139-45.
35. Walsh RM, Woodmansey KF, Glickman GN, He J. Evaluation of compressive strength of hydraulic silicate-based root-end filling materials. J Endod. 2014;40:969-72.
36. Han L, Kodama S, Okiji T. Evaluation of calcium-releasing and apatite-forming abilities of fast-setting calcium silicate-based endodontic materials. Int Endod J. 2015;48:124-30.
37. Chung CJ, Kim E, Song M, Park JW, Shin SJ. Effects of two fast-setting calcium-silicate cements on cell viability and angiogenic factor release in human pulp-derived cells. Odontology. 2016;104:143-51.
38. Lee BN, Son HJ, Noh HJ, Koh JT, Chang HS, Hwang IN, et al. Cytotoxicity of newly developed ortho MTA root-end filling materials. J Endod. 2012;38:1627-30.
39. Dawood AE, Manton DJ, Parashos P, Wong RH, Palamara JE, Stanton DP, et al. The physical properties and ion release of CPP-ACP-modified calcium silicate-based cements. Aust Dent J. 2014;60:434-4.
40. Butt N, Talwar S, Chaudhry S, Nawal RR, Yadav S, Bali A. Comparison of physical and mechanical properties of mineral trioxide aggregate and Biodentine. Indian J Dent Res. 2014;25:692-7.
41. Jang YE, Lee BN, Koh JT, Park YJ, Joo NE, Chang HS, et al. Cytotoxicity and physical properties of tricalcium silicate-based endodontic materials. Restor Dent Endod. 2014;39:89-94.
42. Atmeh AR, Chong EZ, Richard G, Festy F, Watson TF. Dentin-cement interfacial interaction: calcium silicates and polyalkenoates. J Dent Res. 2012;91:454-9.
43. Novicka A, Lipski M, Parafiniuk M, Sporniak-Tutak K, Lichota D, Kosierkiewicz A, et al. Response of human dental pulp capped with biodentine and mineral trioxide aggreagate. J Endod. 2013;39:743-7.
44. Hashem DF, Foxton R, Manoharan A, Watson TF, Banerjee A. The physical characteristics of resin composite-calcium silicate interface as part of a layered/ laminate adhesive restoration. Dent Mater. 2014;30:343-9.
45. Camilleri J. Color stability of white mineral trioxide aggregate in contact with hypochlorite solution. J Endod 2014;40:436-40.
46. Grech L, Mallia B, Camilleri J. Investigation of the physical properties of tricalcium silicate cement-based root-end filling materials. Dent Mater. 2013;29:e20-8.
47. Jiang Y, Zheng Q, Zhou X, Gao Y, Huang D1. A comparative study on root canal repair materials: a cytocompatibility assessment in L929 and MG63 cells. Scientific World Journal. 2014:463826. doi: 10.1155/2014/463826.
48. Alanezi AZ, Jiang J, Safavi KE, Spanberg LS, Zhu Q. Cytotoxicity evaluation of endosequence root repair material. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010;109:e122-5.
49. Chen I, Karabucak B, Wang C, Wan HG, Koyama E, Kohli MR, et al. Healing after root-end microsurgery by using mineral trioxide aggregate and a new calcium silicate-based bioceramic material as root-end filling materials in dogs. J Endod. 2015;41:389-99.
50. Neelakantan P, Nandagopal M, Shemesh H, Wesselink P. The effect of root dentin conditioning protocols on the push-out bond strength of three calcium silicate sealers. International Journal of Adhesion and Adhesives 2015;60:104-108
51. Loushine BA, Bryan TE, Looney SW, Gillen BM, Loushine RJ, Weller RN, et al. Setting peroperties and cytotoxicity evaluation of a premixed bioceramic root canal sealer. J Endod. 2011; 37:673-7.
52. Zhang H, Shen Y, Ruse ND, et al. Antibacterial activity of endodontic sealers by modified direct contact test against Enterococcus faecalis. J Endod 2009;35:1051–5.
53. Vitti RP, Prati C, Silva EJ, Sinhoreti MA, Zanchi CH, de Souza e Silva MG, et al. Physical properties of MTA Fillapex sealer. J Endod. 2013;39:915-8.
54. Salles LP, Gomes-Cornélio AL, Guimarães FC, Herrera BS, Bao SN, Rossa-Junior C, et al. Mineral trioxide aggregate-based endodontic sealer stimulates hydroxyapatite nucleation in human osteoblast-like cell culture. J Endod 2012;38:971-6.
55. Trope M, Bunes A, Debelian G. Root filling materials and techniques: bioceramics a new hope? Endod Topics 2015; 32:86-96.
56. Sundqvist G, Figdor D. Endodontic treatment of apical periodontitis. In: Ørstavik D, Pitt Ford TR, eds. Essential Endodontology. Prevention and Treatment of Apical Periodontitis. Oxford: Blackwell, 1998.
57. Grossman L. Obturation of root canal. In: Grossman L, ed. Endodontic Practice. 10ed. Philadephia: PA: Lea & Febiger; 1982.
58. DeLong C, He J, Woodmansey KF. The effect of obturation technique on the push-out bond strength of calcium silicate sealers. J Endod. 2015;41;385-8.
59. Nagas E, Uyanik MO, Eymirli A, Cehreli ZC, Vallittu PK, Lassila LV, et al. Dentin moisture conditions affect the adhesion of root canal sealers. J Endod. 2012;38:240-4.
60. Gade VJ, Belsare LD, Patil S, Bhede R, Gade JR. Evaluation of push-out bond strength of endosequence BC sealer with lateral condensation and thermoplasticized technique: An in vitro study. J Conserv Dent. 2015;18:124-7.
61. McMichael GE, Primus CM, Opperman LA. Dentinal Tubule Penetration of Tricalcium Silicate Sealers. J Endod. 2016;42:632-6.
62. Felman D, Parashos P. Coronal tooth discoloration and white mineral trioxide aggregate. J Endod 2013;39:484–486.
63. Valles M, Mercade M, Duran-Sindreu F, et al. Influence of light and oxygen on the color stability of five calcium silicate-based materials. J Endod 2013; 39:525–528
64. Govindaraju L, Neelakantan P, Gutmann JL. Effect of root canal irrigating solutions on the compressive strength of tricalcium silicate cements. Clin Oral Invest 2017;21:567-571
65. Watts JD, Holt DM, Beeson TJ, Kirkpatrick TC, Rutledge RE. Effects of pH and mixing agents on the temporal setting of tooth-colored and gray mineral trioxide aggregate. J Endod 2007;33:970–973
66. Neelakantan P, Mohanraj R, Chua E, Belli S. Impact of conditioning regimens and time on adhesion of a fiber post to root dentin using two resin cements. Journal of Adhesion Science and Technology 2015; 29: 337-346
67. Solomon E, Spears R, He J. Retreatability of a bioceramic root canal sealing material. J Endod. 2011; 37:1547-9.

About the Authors
Dr. Chonrada Praisarnti completed her undergraduate training and postgraduate endodontic training from Thailand and Hong Kong respectively. She is into full time private practice focusing on endodontics.

Dr. Jeffrey Wen Wei Chang is a Clinical Assistant Professor of Endodontology at the Faculty of Dentistry, The University of Hong Kong. He also serves as the Undergraduate programme director for Endodontology. Having completed his BED in India and MDS in Hong Kong, he has active research interests in root canal disinfection.

Dr. Prasanna Neelakantan holds an undergraduate and postgraduate conservative dentistry and endodontics degree from India, both with honors. He completed his doctorate program from the University of Amsterdam. Currently Clinical Assistant Professor of Endodontology at the Faculty of Dentistry, The University of Hong Kong, his research passion focuses on endodontic microbiology and root canal filling materials.