the resin that reduce the pulp’s immune response, leading to reduced microbial clearance [131]. It is thus well established that resin‐based adhesives should not be used for VPT [1].
2.4.4 Hydraulic Calcium Silicate Cements
The first clinically available HCSC was MTA, which was developed in the 1990s by Mahmoud Torabinejad [132, 133] and is now widely thought of as the material of choice for managing endodontic problems that require a soft tissue interface with the pulp [9] or periradicular tissues [134]. It was ostensibly developed as an agent to seal the root canal from the periradicular tissues, but was also found to be biocompatible when interfacing with pulpal tissue and showed promise as a therapeutic pulp‐capping material. The first commercially available MTA was ProRoot MTA (Dentsply Tulsa Dental, Tulsa, OK, USA). Its original grey version caused aesthetic problems when it was used for VPT in anterior teeth. A white variety was therefore developed, receiving FDA approval in 2001. It has since become apparent, however, that both versions of ProRoot MTA cause discolouration, and it is recommended that neither be used in the aesthetic zone [135, 136]. MTA is composed of Portland cement (tricalcium silicate, dicalcium silicate, tricalcium aluminate, calcium sulphate, and tetracalcium aluminoferrite in the grey version) and bismuth oxide [137–139].
This material has a number of drawbacks which limit its clinical use, particularly for VPT. These include its tendency to discolour tooth structure [135, 136], its ‘sandy’ consistency, and its long setting time. MTA Angelus (Angelus Soluções Odontológicas, Londrina, Brazil) was the first material to address the latter; it lacks calcium sulphate [137, 138], giving it a shorter setting time of 10–15 minutes [139, 140]. As ProRoot MTA and MTA Angelus are based on Portland cement and thus manufactured from naturally occurring raw materials, it is conceivable that they contain traces of heavy metals such as arsenic, lead, and chromium [138, 141, 142]. In an attempt to prevent this contamination, other manufacturers use pure laboratory‐grade materials. The HCSCs Bioaggregate (Innovative Bioceramix Inc., Vancouver, Canada) and Biodentine (Septodont, Saint Maur des Fosses, France) have been manufactured using this approach. Bioaggregate is composed predominantly of tricalcium silicate, with additions of calcium phosphate, silicon dioxide, and tantalum oxide used as a radiopacifier. Biodentine powder predominantly consists of tricalcium silicate as the core material, along with dicalcium silicate, calcium carbonate (filler), iron oxide (shade), and zirconium oxide (radiopacifier) [143]. It differs from other HCSCs in that its liquid phase has active components, namely calcium chloride (accelerator) and a hydrosoluble polymer (water‐reducing agent) [144]. The manufacturer approximates its setting time at between 9 and 12 minutes [145]. It has been suggested that it is longer in reality, however.
A workable mix of HCSC requires the addition of more water than is necessary for hydration. This results in a system of pores which reduces over time as the water is used up in hydration [146]. Generally, the total pore space is equivalent to the initial water‐to‐powder ratio; therefore, increasing the water‐to‐powder ratio increases the pore space [146, 147]. Ionic exchange between the cement surface and the fluid surrounding it leads to the liberation of a number of different leachable ions from the surface in an aqueous environment.
In order for a material to be regarded as clinically successful as a pulp‐capping agent, it should demonstrate a number of important characteristics, as outlined earlier. Since their introduction, HCSCs have undergone extensive in vitro and in vivo analysis [148]. Their antimicrobial and antifungal effects show conflicting results, with an antibacterial effect found on some facultative bacteria, but no effect on any strict anaerobes; however, the same study showed that zinc oxide‐eugenol‐based materials tested in parallel led to inhibition of growth amongst both types of bacteria [149]. An assessment using single‐strain and polymicrobial broths of bacteria and fungi showed that MTA inhibited fungal and microbial growth in both [150]. Interestingly, grey MTA was shown to inhibit similar amounts of growth of Streptococcus sanguis to white MTA at lower concentrations, suggesting that it may have greater antibacterial activity [151]. Attempts have been made to enhance the antibacterial properties of HCSCs by combining them with chlorhexidine instead of water, at concentrations of 0.12% [152] and 2% [153] – both proved successful, but other authors have expressed doubts about their utility in terms of biocompatibility [154] and deterioration of physical characteristics [153]. Although in vitro microleakage studies are frequently viewed with scepticism [155–157], they are the main means of determining the ability of a material to create a barrier against bacterial penetration in a given clinical scenario. Numerous different in vitro techniques have been used to compare the sealing ability of HCSCs to other materials used in the same clinical situation, with HCSCs showing superior to amalgam, super EBA (ethoxy benzoic acid), and intermediate restorative material (IRM) with techniques including dye leakage [158, 159], fluid filtration [160, 161], and bacterial penetration studies [149, 162, 163].
MTA has been shown to exhibit excellent biocompatibility when it is in contact with pulp wounds in animals [164–168] and humans [9, 109, 169, 170]. Histological studies of iatrogenic exposures in human teeth, managed in aseptic conditions, compared teeth capped with MTA with those capped with calcium hydroxide. Notably, the ones capped with MTA demonstrated greater reparative dentine formation in terms of thickness and quality, less inflammation, and more predictable healing [9, 109, 170]. The precise mechanism by which HCSCs work is not well understood, however. They have been shown to induce key stages in pulp repair, namely pulp cell proliferation [171], migration [168], and differentiation [172]. Immunohistochemical analysis of pulp wounds that had been capped with MTA for up to 11 weeks showed expression of DSPP and collagen type I in those odontoblasts in direct contact with the MTA. There was also evidence of dentine secretion by those same cells [173]. Biodentine has been shown to induce pulp cells to release TGF‐β1, suggesting that this action induces reparative dentine formation [174]. The surface of MTA has been reported to form hydroxyapatite when it is in contact with synthetic body fluids [175, 176]. It is suggested that this biologically accepted surface layer allows for excellent cell/material adhesion and enables superior sealing characteristics when compared with other materials.
Figure 2.8 (a) Diagrammatic representation of dentine, including inorganic and organic components, at a nanometre scale. (b) Immersion of dentine in tissue fluid or extracellular exudate that has interacted locally with calcium silicate cement and has a unique ionic composition. (c) Ionic exchange between dentine and soluble components of calcium silicate cements, resulting in disruption of hydroxyapatite crystals, leading to solubilization and release of bioactive molecules from dECM, including noncollagenous proteins, glycosaminoglycans, and growth factors. (Components in diagrams not to scale.)
HCSCs show many of the properties expected of a VPT agent. It has been clearly demonstrated that they are biocompatible, and even bioinductive. Their interaction with local tissue fluids on the hydrated surface layer is a crucial aspect of this characteristic. Both grey and white MTA leach multiple different cations. From their setting and set phases in vitro and in vitro, this would modify adjacent local tissue fluids. Such fluids have the ability to interact with dentine and can solubilize dECM [43], which contains powerful signal molecules such as TGF‐β1, hepatocyte growth factor, and adrenomedullin (Figure 2.8) [177, 178]. The release of these soluble dECM components leads to cellular events such as proliferation, cell homing, and differentiation in pulp stem cells [177, 178], which are crucial for tissue repair and regeneration. Such a hypothesis is a plausible explanation
