Abstract

Introduction

Vital-pulp-treatment (VPT) procedures are biologically-based therapies aimed at preserving pulp-vitality. Historically, calcium-hydroxide was the 'gold-standard' VPT-material, however, recently a tricalcium-silicate material, ProRoot-mineral-trioxide-aggregate (MTA) has emerged as the material of choice for pulpal-application in permanent teeth. ProRoot-MTA also has drawbacks, including long-setting time, handling-difficulties and post-application crown-discolouration. Relatively recently, another tricalcium-silicate material, Biodentine, has been indicated for VPT.

Objectives

The aim of this review was to compare from relevant laboratory, biological and clinical-studies whether Biodentine is a better material than ProRoot-MTA for use in pulpal applications in permanent teeth.

Methods

A comprehensive MEDLINE search was used to identify manuscripts, which directly compared the materials in relation to dental-pulp applications.

Results

Literature analysis demonstrated that most of the comparative research is in vitro cell-culture studies demonstrating a wide range of methodologies and conflicting findings. In contrast there is a paucity of clinical studies comparing the pulpal response to the materials in permanent teeth. Histological evidence suggests similar pulpal responses, while clinical outcome studies, although preliminary, show equally high material efficacy. Other physical characteristics diverge with Biodentine setting quicker and staining less than ProRoot-MTA, however, the radiopacity of Biodentine is below testing standards making identification difficult.

Conclusions

Biodentine does present an evidence-based biologically-based alternative VPT material to ProRoot-MTA. Future research should be directed at long-term clinical outcome studies and the interaction of Biodentine with the dentine matrix.

Introduction

Exposure of the pulp is a common clinical occurrence due to trauma, caries or iatrogenic reasons. The pulp is protected by an outer shell of enamel and dentine; when this protection is breached the pulp is colonised by microbes with the simulation of a pulpal inflammatory response.1 If the pulpitis is untreated, ultimately, pulp necrosis occurs.2 Pulp vitality can be maintained if the irritant stimulus is removed and the tooth restored.1 The importance of retaining all or part the pulp has been highlighted as it is more conservative, less technically demanding and more biologically-based compared with pulpectomy procedures.3,4

The aim of the vital pulp treatment (VPT) is to preserve the vitality and function of the pulp, while stimulating hard tissue repair processes.5,6 VPT encompasses procedures with no pulp tissue removal, ie pulp capping (indirect and direct) as well as techniques with varying degrees of pulp excision, that is, pulpotomy (partial or complete).5 Several factors influence the success of VPT procedures including the level of pre-operative pulp inflammation,7 the post-operative prevention of further microbial insult8 and the material used to interface with the biological tissue.9 Historically, VPT was considered as an unpredictable procedure.10 Calcium hydroxide has been the material of choice for many years,11,12 but is limited by poor mechanical properties, non-specific mechanism of action,13 absence of sealing properties14 and incomplete hard tissue formation over the pulp wound.8,9 Developments in our understanding of pulp defence mechanisms4 and the advent of tricalcium silicate materials have created new opportunities and enthusiasm for VPT.15 The tricalcium silicate, mineral trioxide aggregate (MTA), has demonstrated superior histological9,16 and clinical outcome compared with calcium hydroxide in VPT procedures.17

The original, most researched and, within the United Kingdom, the market leading commercial MTA product, ProRoot MTA (Dentsply Sirona, Ballaigues, Switzerland), is not an ideal material with several disadvantages highlighted including a long-setting time, tooth discolouration and high-cost.17,18,19,20 New generation tricalcium silicate-based cements have been introduced, which attempt to address many of the shortcomings of ProRoot MTA. Biodentine (Septodont, Sant-Maur-des-Ditch Cedex, France) is a tricalcium silicate cement marketed specifically for use in VPT procedures. Publications have highlighted its positive effects on pulp mineralisation processes, shorter setting-time, improved mechanical resistance and ease of use compared with ProRoot MTA for use in VPT procedures.21,22,23,24

ProRoot MTA is chemically composed of Portland cement with bismuth oxide added as a radiopacifier.25 There are now a range of other commercial MTA products available, including Angelus MTA and Angelus HP (The Angelus, Londrina, Brazil), MM–MTA (Micro-Mega, Besancon, France), Retro/ Ortho MTA (BioMTA, Seoul, Republic of Korea) and MTA Plus (Avalaon Biomed, Houston, USA), which share the presence of di and tricalcium silicates, as well as radiopacifiers.26 These products vary in their radiopacifiers (bismuth oxide, zirconia, calcium tungstate and tantalite), but also have minor differences including the presence of calcium sulphate, calcium carbonate and phyllosilicates.26 Biodentine is similar to ProRoot MTA, but does not contain calcium aluminate, calcium sulphate or bismuth oxide, while zirconium oxide is the radiopacifier.26 The absence of bismuth oxide in Biodentine is significant not only for radiopacity, but also for other properties such as staining potential, setting time and micro-hardness.27,28 Due to differences in chemical formulation a recent review has suggested that these materials could be grouped as 'bioactive endodontic cements (BECs)' rather than calcium silicate materials.29

From a reparative perspective, the role of the odontoblast cell is critical, forming the primary dentine during development, secondary dentine throughout the life of the tooth and when challenged the deposition of tertiary dentine in an attempt to 'wall off' the irritation.30 Depending on the severity of the stimulus, tertiary dentine deposition can be reactionary or reparative.31 Reactionary dentine being formed by an upregulation of surviving post-mitotic odontoblasts exposed to the influence of relatively mild stimuli, while reparative dentine is formed generally after a stronger stimuli, which has led to death of the odontoblast cell.31,32 At a cellular level reparative dentine is believed to be produced following cyto-differentiation of pulpal progenitor cells and the formation of a new generation of odontoblast-like cells.31,32 Alternative theories suggest that other cells such as fibroblasts may cyto-differentiate to produce the mineralised tissue.33 The cellular differentiation is likely to be guided by the influence of growth factors and bioactive molecules derived from both the dentine and the pulp matrix.34,35 Although reactionary and reparative dentinogenesis are for didactic purposes considered separately, in the event of pulp exposure reparative dentine will form the mineralised bridge, while at the periphery of the cavity reactionary dentinogenesis will occur simultaneously.3

Inflammation is also an important stimulus to drive the reparative process with odontoblasts involved in initial sensory stimulus transmission from the dentine and also an immunocompetent role in cellular defence.36,37 Indeed the low level release of inflammatory mediators such as interleukins (for example, IL–1α, −1β, −2, −6) in mineralising cells in contact with MTA supports the need for a degree of inflammation in promoting regenerative processes.38 A wide range of bioactive dentine matrix components are 'fossilised' in the mineralised tissue being released into pulp during caries or trauma.3,39,40 Demineralisation of dentine and indeed contact with materials such as Pro Root MTA, calcium hydroxide and other agents release a plethora of bioactive molecules including members of the TGF–β superfamily which can stimulate a complex cascade of molecular events that promote pulp repair.34,41,42,43 Notably, no evidence suggests that Biodentine is capable of sequestering dentine matrix components so comparative bioactivity analysis with ProRoot MTA is not possible.

Using biologically-based dental materials that promote the healing process are paramount in vital pulp therapy and other irrigation strategies are being developed which enhance the release of bioactive molecules from dentine to improve the wound repair.44,45 Over the last ten years, tricalcium silicate materials, including ProRoot MTA and Biodentine, have demonstrated superior histological response compared with the gold standard material calcium hydroxide in VPT.9,24 It is assumed that tricalcium silicates work more efficiently than calcium hydroxide and in a similar way to each other (Fig. 1).13,24 ProRoot MTA and Biodentine have shown the capacity to promote the early synthesis of reparative dentine, perhaps due to enhanced regulation of TGF-F-β1, osteopontin and other growth factors.23,24

Figure 1
figure 1

Schematic theoretical representation of the process of reparative dentinogenesis after a VPT procedure using calcium silicate cement

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The aim of this review was to comprehensively analyse only the laboratory and clinical studies which compared the most commonly used and researched tricalcium silicate materials, ProRoot MTA and Biodentine, specifically in relation to the dental pulp.

Review

Search strategy

A comprehensive MEDLINE search up to November 2017 was conducted using medical subject headings (MeSH) in combination with 'and' or 'or'. The major MeSH terms searched were 'Endodontics', 'Dental Pulp Disease', 'Dental Pulp Test', 'Pulpotomy' and 'Dental Pulp Capping'. In addition, the following terms were added 'Biodentine', 'Mineral Trioxide Aggregate', 'MTA', 'calcium silicate cements', 'calcium silicate materials', 'calcium silicates' as well as 'di and tricalcium silicates'. Bibliographies of all relevant papers and previous review articles were hand-searched for further studies of relevance. Any relevant work published in the English language and presenting pertinent information related to this review was considered for inclusion. Titles were excluded if they were conference reports. Laboratory (biocompatibility, biological, material aspects) studies were considered if Biodentine and MTA were compared within the same study. Clinical studies focused on comparative responses in permanent teeth.

How are the success of ProRoot MTA and Biodentine in VPT procedures compared clinically?

The aim of VPT is to maintain the vitality of the tooth in the absence of an apical radiolucency and, in case of immature teeth, achieve apexogenesis. Therefore, outcome should be assessed from both a clinical and radiographic perspective.5,46 Clinically, the treated tooth should respond positively to pulp sensibility testing (if possible to assess) and not present any sign or symptoms such as pain, tenderness to percussion or presence of a sinus tract.6,47 The radiographic examination should demonstrate no signs of apical periodontitis, no evidence of internal resorption, present evidence of mineralised bridge formation and continued root development in immature teeth.6,48,49 A follow-up appointment no longer than six months postoperatively is recommended and a recall of one year; long-term follow up is also required to assess the success of the procedure.6

VPT materials should ideally be compared in adequately powered, randomised clinical trials (RCT), which are free from bias.17,50,51,52 The clinical performance of new materials can also be investigated, but not compared in case series and case reports.53,54,55 Clinical trials comparing ProRoot MTA and Biodentine pulpotomy procedures in carious deciduous molars have demonstrated that the two materials have equally effective outcomes in young patients.57,58 Unfortunately, there is a paucity of clinical studies comparing the outcome of Biodentine and ProRoot MTA in VPT procedures in permanent teeth. One recent RCT compared Biodentine and ProRoot MTA as pulp capping materials in asymptomatic cariously-exposed permanent molar teeth and reported no difference between the materials after one-year recall.59 In this study, 169 patients with carious exposures of one permanent molar were treated with calcium hydroxide, ProRoot MTA or Biodentine with no significant differences between the materials and very few failures reported in any of the experimental groups at one year, however, for practical reasons (handling, placement) it was concluded that Biodentine and ProRoot MTA offered advantages over calcium hydroxide.59 This clinical trial investigated tricalcium silicate pulp capping on carious exposures in permanent teeth of a young patients (seven to 16 years), which by the author's admission contained significant numbers of teeth with open apices59. To homogenise the patient sample other studies investigated VPT procedures in older patients, 15 to 30 years and 18 to 40 years.60,61 A small clinical trial of 24 patients with cariously exposed molars were pulp capped with either Biodentine or ProRoot MTA and reviewed up to six months; ProRoot MTA was reported to perform better but the results were not significantly different.60 Another small retrospective pulp capping study investigating the two materials in carious molars concluded after 18 months that both materials performed predictably and equally, however care must be taken in extrapolating the results because the sample size in both studies was inadequate to potentially recognise any statistical difference between the materials.61

From the limited evidence available, the success rate for VPT procedures is high with both materials, however, existing studies are preliminary, limited by small numbers and short follow-up period, and only investigate pulp capping, not pulpotomy procedures. Other important clinical variables including calcium silicate-associated discolouration was only reported in one study.61

How are Biodentine and ProRoot MTA compared in the laboratory with respect to the pulp?

The majority of research comparing the histological response to VPT materials is carried out in sound teeth, which limits confounding factors and enables comparison, but decreases the clinical relevance of the study.33,62 Recruiting human subjects who are prepared to consent to a VPT procedure on a sound tooth before later scheduled extraction is challenging and as a result the majority of ex vivo studies are carried out using animal models, which have their own limitations.63,64,65 Several qualitative and quantitative ex vivo human studies comparing a range of VPT materials have been published.9,16,23,66,67 These studies should carefully evaluate histologically with serial sections the soft tissue response – inflammation, necrosis, odontoblast-like cell presence, bacterial infiltration, pulpal calcifications – as well as hard tissue bridge formation, recording its thickness, homogeneity and the cellular interface with the materials.9,23 Cone-beam computed tomography (CBCT) has been used to assess the hard tissue bridge before the histological exam.67 One recent histological study compared Biodentine and ProRoot MTA (as well as calcium hydroxide and composite resin) and concluded that both ProRoot MTA and Biodentine materials induced a similar mineralised bridge formation at the pulp-material interface. The bridges from Biodentine and ProRoot MTA were homogeneous and with minimal tunnel defects.67

In addition to a limited number of ex vivo studies, other in vitro biological studies have compared Biodentine with ProRoot MTA within the same study (Table 1). There have been cell culture studies using primary cells (rodent or human dental pulp cells) or odontogenic cell lines (for example, MDPC–23), which analyse cellular processes such as cytotoxicity, migration, viability, differentiation, inflammation and mineralisation (Table 1).21,68,69,70,71 Although these laboratory studies represent the majority of research on this subject, unfortunately, it is not possible to conclude from these biological studies comparing Biodentine and ProRoot MTA that one material is consistently better than the other (Table 1).

Table 1 Biological laboratory in vitro studies comparing the efficacy of ProRoot MTA (PrMTA) and Biodentine (BD) within the same publication
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How do Biodentine and ProRoot MTA compare to the criteria for an ideal VPT material?

If additional evidence is collated from clinical, ex vivo and in vitro studies and analysed with respective to Ingle's criteria, (Table 2) it is evident that Biodentine compares equally to ProRoot MTA for reparative dentine formation, maintaining pulp vitality, anti-bacterial properties, long-term insolubility and preventing coronal leakage.23,50,67,73,74,75,76,77 Notably, Biodentine performed consistently better than ProRoot MTA in adherence to dentine measured by push-out testing, however, ProRoot MTA was more radiopaque than Biodentine, which consistently fell below ISO standards (Table 2).76,78,79 Certainly within these studies Biodentine compares favourably to ProRoot MTA and both tricalcium silicate materials are superior to other materials tested including glass ionomer cement (GIC), Dycal (calcium hydroxide), Theracal (resin-modified tricalcium silicate), Calcimol (calcium hydroxide), Calcicur (calcium hydroxide) and zinc-oxide eugenol cements such as IRM.

Table 2 Laboratory and clinical comparison of ProRoot MTA (PrMTA) and Biodentine (BD) as an ideal material for vital pulp treatment according to criteria listed in Ingle's Endodontics (Bogen & Chandler 2008)73
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How are the practical aspects of Biodentine and MTA compared in the laboratory and clinic?

Crown discolouration as a result of VPT does not signify a failure of the procedure, however, patients are understandably concerned about potential shade change and staining issues as a result of any dental treatment.6 Comparative studies carried out on extracted teeth (animal and human) have concluded that Biodentine has less staining potential compared with ProRoot MTA (Table 3).80,81,82,83

Table 3 Comparison of practical issues and drawbacks of Biodentine (BD) and ProRoot MTA (PrMTA) investigated in vivo and in vitro
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Initially, ProRoot MTA was only available in a grey formulation, which was later superseded by a white formula for use in aesthetic areas. White ProRoot MTA has been demonstrated to discolour teeth, particularly in the presence of sodium hypochlorite and blood.18,84,85 This discolouration has been attributed to the radiopacifier bismuth oxide.27 The anaerobic environment of the root canal system and light irradiation have been reported to enhance formation of stains, while presence of oxygen reduces discolouration.80 Biodentine contains zirconium oxide rather than bismuth oxide, which has been attributed to reduced colour change in Biodentine treated teeth.86,87,88 While, it is acknowledged that tooth discolouration remains possible with all tricalcium silicate materials, particularly in the presence of blood products, in general Biodentine induced staining significantly less than ProRoot MTA or MTA Angelus.89,90 Indeed, only one study reported that Biodentine induced a higher incidence of stains than ProRoot MTA (Table 2).91 Although the absence of the radiopacifier bismuth oxide in Biodentine has been attributed to the lack of discolouration, the radiopacity of Biodentine is consistently reported as being below ISO 6876 standard of 3 mm of equivalent aluminium for a 1 mm thick sample, and indeed cannot be clearly visualised as distinct to dentine by the operator.76,92,93

An important practical limitation of ProRoot MTA is the time taken to set.94,95 This process takes several hours. As a result new calcium silicates such as Biodentine were developed to reduce this time with a setting time of 12 minutes claimed by the manufacturers. This shortened setting time is not predictable, however, with times of up to 100 minutes reported.76,96 Direct comparison of setting times between studies is problematic to compare as the ISO methods require careful training and execution. For instance Biodentine may not set as quickly as the manufacturer claims, but it does set faster than ProRoot MTA.76,94,97,98 One study reported a similar setting time between that MTA Angelus and Biodentine.99

ProRoot MTA has been reported to be difficult to handle, while Biodentine is considered easier to mix and use.94,98,99,100 Many dentists avoided using any calcium trisilicate materials in VPT, citing cost, lack of training and difficulties in handling.19

Conclusions

The choice of material for pulpal application is critical with tricalcium silicates established as the gold standard. Comparative analysis of Biodentine and ProRoot MTA within this review revealed a plethora of biological in vitro studies, with a range of methodologies and conflicting findings, however, both materials' pulpal interaction is consistently better that other materials investigated. There are a small number of short-term, but no long-term clinical studies comparing the pulpal response to the materials in permanent teeth. Of the available evidence, histological evaluation highlights a similar response, while VPT outcome studies, although preliminary and under-powered, show high material-efficacy. Currently, practical issues consistently separate the materials, with ProRoot MTA causing more tooth staining, but having greater radiopacity than Biodentine. In the future, there is an urgent need for well-designed, adequately-powered, clinical trials in this area, as well as improved functional understanding of the interaction of Biodentine with the dentine-matrix.