Premixed bioceramics: A novel pulp capping agent

Abstract

The main aim of restorative dentistry is to protect the vitality of the Pulp tissue. The pin point carious expoure and iatrogenic errors warrant the need for various pulp capping procedures like Indirect Pulp Capping and Direct Pulp Capping. Pulp Capping is dressing of the dental pulp exposed due to mechanical procedure, carious lesion or traumatic injury to preserve its vitality and function. There has been constant evolution and research on materials used to cap the Pulp tissue. The different kind of chemical and biological materials has been used with varying degree of success. The prognosis based on the pulp capping material has dramatically improved with the introduction of bioactive cement. Though MTA and biodentine have shown a high success rate, their properties can be adversely affected with error in powder/liquid ratio and may present with difficulty in the handling characteristic. Premixed bioceramics have been introduced in the market and present with desirable properties as a pulp capping agent. Owing to good handling characteristics, biocompatibility, odontogenic property, and antibacterial action it is a potent pulp capping agent for clinical application. This review is aimed to discuss the introduction of premixed bioceramics, forms of premixed bioceramics available, and its physical, chemical, and biocompatible properties.

INTRODUCTION

Miguel de Cervavntes, one of the greatest Spanish writers, in 1605 quoted “Every tooth in a man's head is more valuable than a diamond.”[1] This highlights the importance of preservation of tooth and its constituents including pulp. Pulp capping is defined as “treatment of an exposed vital pulp in which the pulpal wound is sealed with a dental material, such as calcium hydroxide or mineral trioxide aggregate (MTA), to facilitate the formation of reparative dentin and maintenance of a vital pulp.”[2]

Healthy pulp has a key role throughout the living of a tooth due to the innate capacity to repair and return back from diseased state. With the advent of standardized standard operating procedure in conjugation of newer cement and adhering to strict protocols of disinfection, emphasis has shifted from “doomed organ” concept to that of “predictable repair and recover.”[3,4]

The ideal pulp capping agent should preserve the pulpal vitality and encourage reparative dentin formation. For 100 years thereafter, various different kinds of chemical and biological materials such as gold, lead, zinc oxide sulfate cement, zinc oxide chloride cement, phosphate cement, gutta-percha, carbolic acid, cork, celluloid, asbestos, and zinc oxide eugenol cement have been used to cap the pulp with varying degree of success.[5]

In 1920, Hermann introduced calcium hydroxide to dentistry. Although calcium hydroxide was not developed as a pulp capping agent, Hermann used it as a pulpotomy material to prove its biocompatibility. He reported that calcium hydroxide is biocompatible to keep tissues of the pulp vital without compromising its functions and also promote the formation of hard tissues. However, calcium hydroxide had its disadvantages. Calcium hydroxide does not seal the exposed pulp completely from the outside environment.[6] The quality of tertiary dentin formed is poor with calcium hydroxide. The osteodentin produced after application is incomplete and thus results in voids and so-called tunnel defects. It provides a chance for bacterial contamination compromising the result of the intended treatment.[7] Some more to add to drawbacks were high solubility in the oral fluid which leads to the dissolution of the cement over an extended period and degradation after acid etching.[8] The calcium hydroxide cement was thus not easily accepted as a pulp capping material initially.

Clinical retrospective investigation found a variable success rate over 2–10-year period for direct calcium hydroxide pulp capping. Dammaschke et al. reported an overall survival rate of 76.3% at a mean 6.1-year follow-up.[9] Auschill et al. reported a success rate of 61%.[10] Willershausen et al. evaluated 1075 teeth capped with calcium hydroxide and reported success of 80.1% at 1 year, 68% for 5 years, and 58.7% after a 9-year period.[11] Although there were compromised properties, the lack of other new materials and promising clinical results led to continued use of this material as a gold standard in pulp capping for more than 50 years and of the preferred universal material till date.

The compromised results of pulp capping in the past can be attributed to improper case selection, incorrect diagnosis, incomplete caries removal, and lack of newer materials to promote reparative dentin formation and regenerative potential. Consequently, the search of an ideal material to cap the pulp leads to other biomaterials suggested in the literature most commonly being the calcium silicate based such as MTA and Biodentine.[12] Other materials reported are tricalcium phosphate ceramic, collagen, bonding agents, hydroxyapatite, growth factors, various enzymes, propolis, novel endodontic cement, Emdogain, TheraCal, and EndoSequence.[8,13] Among all the materials tried and tested, MTA showed a promising and exceptionally high success rate as a pulp capping material. In an observational study by Bogen G et al., 97.66% of teeth exhibited a favorable outcome.[14] Suhag et al. in 2019 reported a success rate of 93% with ProRoot MTA pulp capping in carious pulpal exposure.[15] Linu et al. in 2017 reported an overall success rate of 88.5% with MTA and Biodentine.[16] The enhanced survival outcomes seen with MTA or Biodentine can be attributed to the changes in established treatment protocols and favorable composition of improved pulp capping materials.

Capping material is one of the factors to determine the success of the treatment, however, it should not be considered as a sole criterion. According to cohen and combe, the ideal pulp capping material should - maintain pulp vitality, stimulate reparative dentin formation, bactericidal or bacteriostatic, adhere well, provide Bacteria tight seal, sterile, able to resist forces under restoration and preferably be radiopaque.”[17] Till today, no material has been developed which possesses all these properties, though calcium silicate cement like MTA have maximum properties among those mentioned above. MTA having a predictable success rate, it is not immune to drawbacks and disadvantages. MTA is supplied in powder and liquid formulation which require mixing before use. Mixing was variable depending on operator use and not uniform if handled incorrectly. Thus, drawbacks with MTA cement were difficult manipulation, difficult handling characteristics, technique sensitive, discoloration, and longer setting time. To overcome these shortlisted drawbacks of MTA, the search for newer material with uniform and easy handling characteristic lead to the development of the most recent premixed bioceramic or premixed calcium silicate cement.[18,19,20,21]

To date, most of the data have been published regarding the use of these premixed bioceramic materials used as root canal sealers and in conjugation with obturation. There was a scarcity of review literature with respect to these materials been used as a direct pulp capping agent, though recommended by the manufacturer. This review is aimed to describe the role of premixed bioceramics as a pulp capping agent.

PREMIXED BIOCERAMICS

In the past 50 years, bioceramics have been extensively used in medical sciences for the replacement of joints, bone tissues, heart valves, and cochlear replacement. In dentistry, these materials were introduced for their odontogenic/osteogenic properties.[22] Bioceramics are chemically stable, inorganic, biocompatible materials.[23] Bioceramics can be divided into:

1. Bioinert – Which are not interactive with biologic systems, for example, alumina and zirconia

2. Bioactive – Which shows interfacial interactions with adjacent tissue; for example, Bioactive glass and glass ceramics

3. Biodegradable – Which ultimately replace or are incorporated into tissues. for example, calcium silicates.[24]

Calcium silicate-based materials mainly consist of dicalcium or tricalcium or tetracalcium silicate with hydration process as a basic setting mechanism. The novel premixed bioceramics consist of “calcium silicates, zirconium oxide, tantalum oxide, calcium phosphate monobasic, and fillers.” They have superior mechanical and biological properties. They are ready to use materials, with superior handling properties. Premixed bioceramics are hydrophilic in nature and necessitate moisture from the adjacent tissues to set. These are classified based on their consistency with all having similar composition.[25]

1. Syringe form

2. Putty form

3. Fast-set putty form.

ADVANTAGES OF PREMIXED BIOCERAMICS

1. Premixed, thus ready to use product without prerequisite to mix and manipulate avoiding operator error

2. Premixed materials have the benefit of homogenous consistency

3. Only required quantity of material can be dispensed and thus avoids waste of material

4. No cross-contamination

5. Easy delivery to nonaccessible areas

6. Superior handling characteristic

7. Easily condensable

8. They are insensitive to moisture and blood contamination and consequently are less technique sensitive

9. Upon setting, they become hard and expand slightly providing with superior long-term seal.[26]

Due to these advantages, premixed bioceramic materials are recommended for procedures such as pulp capping, pulpotomy, perforation repair, root-end filling, and obturation.[27]

There are three premixed bioceramics currently available till date, with chemical similarity but dissimilar trade names as per the countries they are manufactured in:

1. iRoot BP (Innovative Bioceramics, Vancouver, Canada) [Table 1]

2. EndoSequence root repair (Brasseler USA, Savannah, GA) [Table 2]

3. TotalFill (FKG Dentaire SA, Switzerland) [Table 3].

Table 1.

Availability of iRoot BP (Innovative Bioceramics, Vancouver, Canada)

Material	Available as	Setting time (h)
iRoot® BP Plus putty	-	2
iRoot BP	Preloaded 0.5 g syringe	2
iRoot SP	1 ml syringe	2
iRoot FS	-	Within 1

Table 2.

Availability of TotalFill (FKG Dentaire SA)

Formulation	Available as	Setting time (h)
TotalFill BC RRM paste	1 g syringe	2
TotalFill BC RRM putty	2.5 g preloaded jar	2
TotalFill BC RRM-fast-set putty	0.3 g syringe	2

BC RRM: BC root repair material

Table 3.

Availability of EndoSequence (Brasseler USA, Savannah, GA)

Formulation	Available as	Setting time
EndoSequence BC RRM	1.5-2 g syringe	2 h
EndoSequence BC RRM putty	1-3 g	2 h
EndoSequence BC RRM-fast-set putty	0.3 g syringe	20 min

BC RRM: BC root repair material

PREMIXED BIOCERAMICS AS A PULP CAPPING AGENTS

Biocompatibility

Cell apoptosis/cytotoxicity

Dou et al. using an Annexin V/propidium iodide assay evaluated apoptosis of Human Dental Pulp Cells. They concluded that apoptotic cells were higher in the Ca(OH)₂ group than in iRoot BP, MTA, and Colony Growth Factor groups. When compared to MTA, iRoot BP exhibited a near to similar apoptotic rate.[28] Eldeniz et al. evaluated genotoxicity and cytotoxicity of various sealers including iRoot SP with new silicate-based sealer. Using lentiviral gene transfer of human telomerase reverse transcriptase (hTERT) concluded that iRoot SP showed lesser toxicity compared to MTA.[29]

Antimicrobial activity

ElReash et al. using agar diffusion test reported that iRoot BP Plus exhibits antimicrobial action against Streptococcus mutans, Staphylococcus aureus, and Enterococcus faecalis which is a requisite for being pulp capping agent. They also found that its pH was 12.1 after 5 min and 11.9 after 60 min and therefore is alkaline in nature.[30] Elshamy et al. compared antimicrobial activity of MTA, calcium hydroxide, and EndoSequence root repair material (ERRM) against salivary mutans streptococci and lactobacilli. They found that ProRoot MTA and ERRM had superior antimicrobial activity than Ca(OH)₂. This can be credited to its high pH (12.5), hydrophilicity, and active calcium hydroxide diffusion.[31]

Cell viability and proliferation

Various studies have evaluated cell viability and proliferation using flow cytometry, 3- (4,5-dimethylthiazol-2-yl)-5- (3-carboxymethoxyphenyl)-2- (4-sulfophenyl)-2H-tetrazolium or fluorescent dyes, CCK-8, 3- (4,5-dimethlythiazol-2-yl)- 2,5-diphenyl tertrazolium bromide etc. Chen et al. compared the effect of ERRM and gray ProRoot MTA on hDPSCs which were cultivated over cement. They found on MTT that after 3 and 5 days ERRM showed greater cell proliferation than Grey MTA.[32] Machado et al. using flow cytometry showed that ERRM had similar cell viability as compared to gMTA.[33] Oncel Torun et al. using XML Tunneling Technology (XTT) assay found that iRoot BP showed more cellular viability than wMTA in 1:1 dilution.[34] Zhang et al. compared iRoot BP Plus, BioAggregate, and ProRoot MTA and showed that after 1 day BioAggregate, iRoot BP Plus than ProRoot MTA had greater cell proliferation while using hDPCs derived from extracted permanent molars.[35]

Odontogenic properties

Several in vitro and in vivo studies had been conducted in both animals and humans to evaluate the odontogenic properties of these cement. Assessments in laboratory studies can be done by detecting odontogenic markers using fluorescence microscopy, detecting calcium by Alizarin test, determining odontogenic genes by Enzyme Linked Immunosorbent Assay (ELISA), polymerase chain reaction (PCR), or Western blot. In vivo evaluation can be done by evaluating the density, volume, and thickness of dentinal bridge formation by various tests.

In vitro studies

Machado et al. using Alkaline Phosphtase (ALP) assay found that after 10 days ERRM and gray ProRoot MTA showed comparable odontogenic activities.[33] Oncel Torun et al. using real-time quantitative-PCR measured the expression of mineralization-related genes, i.e., Bone Morphogenic Protein (BMP), bone sialoprotein, dentin sialophosphoprotein, osteonectin, osteopontin, and collagen type I and found that mineralization potential of iRoot BP was comparable to white MTA.[34]

Animal studies

Dentinal bridge formation is a prerequisite and by far the most essential criterion for the success of pulp capping agent. Shi et al. in an animal study found that after 4 weeks of placement of iRoot BP Plus, dentinal bridge formation was seen at interface of exposure pulp. Histological examination showed no inflammation and no multinucleated giant cells around the material. At 3 months, results showed that there was >75% bridge formation showing irregular tubules in histological sections.[36] Liu et al. conducted a study in rats for assessing amount of dentin bridge formation and showed that at 1 week, mild bridge formation was seen in greater number of samples of iRoot BP Plus than in ProRoot MTA and thick bridge formation was seen after 4 weeks.[37] Okamoto et al. using microcomputed tomography analysis of tertiary dentin confirmed that some ProRoot MTA samples had little defects and there was a lack of continuity whereas iRoot BP had no defects.[38]

Human studies

More recently, Rao et al. studied the effect of iRoot BP Plus and Ca(OH)₂ as pulpotomy material in cases of complicated crown fracture in permanent incisors and reported that iRoot BP Plus produced reparative dentin bridge within 6 weeks, and the majority of dentin bridges had no tunnel defects.[39]

Physical and chemical properties

Setting properties

Earlier premixed cement had setting time of 2 h. Later, to decrease the long setting time and complete procedure in minimum appointment, manufacturers developed more efficient new rapid set putty which sets in approximately 20 min. Initially, tartaric acid was used as an accelerator but had been shown to be cytotoxic. Xu et al. evaluated the use of malic acid, glycolic acid, citric acid, and malonic acid as accelerators and found that glycolic acid greatly reduced the setting time. The accelerator used had a great effect on the strength and cytotoxicity of material.[40] According to the manufacturer, these cement require moisture from surroundings, i.e., fluid from dentinal tubule. Loushine et al. established that excessively wet environment may affect the setting time and unfavorably affect the microhardness of the material after setting. Therefore, setting time may be affected in conditions such as smear plugs and/or tubular sclerosis.[25]

Radiopacity

It is advantageous to use materials having radiopacity values similar to or higher than that of enamel for better quality performance.[41] Firoozmand et al. found that enamel and dentin has radiopacity of 0.91 mm and 0.63 equivalent of Al, respectively.[42] Hrab et al. compared radiopacity of TotalFill BC sealer with hydroxyapatite with zinc (5%–10%), hydroxyapatite with silver (10%–15%), aluminosilicate glasses (45%–50%), zirconium oxide (10%–15%), and calcium hydroxide (5%–10%) and found that TotalFill had Radiopaque of average 4 ± 0.15 (unit) which was greater radiopacity than experimental materials.[43] Furthermore, studies are required for assessing the radiopacity of these materials.

Strength

Compressive strength is an essential requisite that may affect the clinical performance of the material. Compressive strength is an indirect determinant of the setting mechanism of material. Walsh et al. compared the effect of fetal bovine serum and saline over compressive strength of ERRM with MTA plus and found that compressive strength of premixed ERRM was less influenced by contact to biological fluids. This can be attributed to fact that ERRM was premixed by the manufacturer and provides a more uniform mixture. MTA requires chairside manual mixing that may have inconsistency within the material.[44]

Marginal adaptability and sealing ability

The material intended to use as a capping agent should provide a tight seal against microorganisms and prevent the entry of any fluid toward pulp tissue. Any kind of gap leading to leakage will result in secondary caries, affecting the extended prognosis of the procedure. Lagisetti et al. using methylene blue dye test compared microleakage of EndoSequence BC RRM-fast-set putty, ProRoot MTA, and Zirconomer and stated that EndoSequence BC RRM-fast-set putty had less microleakage as compared to other groups. This can be attributed due to its improved putty consistency that allows better adaptation to cavity walls. It also contains nanoparticles which permit improved penetration into dentinal tubules.[45] Similarly, Antunes et al.[46] and Jeevani et al. found similar results in accordance with this study.[47] However, Hirschberg et al. found a contrary result where MTA showed less microleakage than ERRM.[48]

Adhesion

ERRM shows micromechanical adhesion to dentin. Scanning electron microscope studies have shown microtag formation into dentinal tubules. However, no such study has been conducted about the bond strength of material.[49]

CONCLUSION

The premixed bioceramic materials possess favorable results and all the properties comparable to the currently recommended material for pulp capping, MTA. Although the results are comparable or even superior, the material is recently introduced and thus there are lesser data and very few clinical trials to ascertain it as an alternative option to MTA. As a material to be successful for pulp capping agent, the restorative material should be evaluated on a long-term basis of 5–10 years, which is lacking with these materials. Till date, it can be concluded that premixed bioceramics can be used as a pulp capping material.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.