these properties, but in recent years significant advances have been made. Recently used pulp‐capping agents will be considered in this section.
2.4.2 Calcium Hydroxide
Numerous different materials have been used as pulp‐capping agents over the years, with varying degrees of success. However, generations of clinicians have gone back to using calcium hydroxide, which until recently was considered the gold standard [9], and is probably still one of the most common materials found in dental surgeries all over the world. This material has been in use for over 100 years [97], and it has been intensively researched during that time [71, 90,98–103]. Indeed, direct pulp‐capping studies using calcium hydroxide on nonexperimental pulp exposures that are carious or induced by trauma have demonstrated clinical success rates of 80–90% [87, 104].
There is still considerable debate about its mode of action; numerous animal studies have shown histological dentine bridge formation in 50–87% of treated teeth [89105–108], but this is less predictable in humans [9, 109, 110]. It has been suggested that the action of calcium hydroxide is related to its caustic nature; it has a high pH of 11–12, which initially induces tissue irritation and superficial necrosis (known as a zone of coagulation necrosis) [98].
For clinical application, calcium hydroxide is either mixed as a pure powder with an aqueous solution (water or saline) or, more commonly, used as a commercially available hard‐setting wound dressing/lining material, such as Dycal (Denstply Caulk, Milford, DE, USA) or Life (Kerr, Boggio, Switzerland). Dycal and Life set through an acid–base reaction leading to the formation of Ca‐salicylate chelate, although they use different setting activators (butyleneglycol disalicylate and methyl salicylate, respectively). Both show a marked calcium release.
Aqueous suspensions have been shown to induce wider zones of necrosis compared with commercial preparations [89]. In a histological study in rhesus monkeys [89], wound healing occurred at the material interface when commercial preparations were used, but for calcium hydroxide paste made with saline, the reparative tissue formation was some distance away from the material itself, leaving a persistent vacant zone. The hard‐setting materials resulted in less evidence of caustic damage, and it appears that the necrotic zone was removed by phagocytosis and replaced with granulation tissue [90]. In a more recent study in humans [111], one week of pulp capping with calcium hydroxide resulted in a moderate inflammatory infiltrate, disorganized tissue with hyperaemia, and no evidence of a hard tissue barrier. At one month, the majority of samples showed a reduced inflammatory response with evidence of dECM components secretion and partial hard tissue repair. This is consistent with earlier reports suggesting that hard tissue healing next to calcium hydroxide was unpredictable and not complete across the wound, with numerous tunnel defects present [112].
The mechanisms by which calcium hydroxide induces hard tissue repair are not entirely understood [113]. It has been suggested that the superficial necrotic layer separates the vital tissue from the wound so that the pulp can repair itself [71]. Others have postulated that it is the creation of a supersaturated environment of calcium ions adjacent to the pulp that induces hard tissue healing, but this hypothesis was disproved when it was demonstrated that the calcium ions which were incorporated into the mineralized hard tissue bridge originated from the underlying tissues rather than from the pulp‐capping material itself [114, 115]. It has also been proposed that the tissue may respond favourably to the high‐pH environment created by the release of hydroxyl ions [116]. Without doubt, the bactericidal nature of calcium hydroxide, brought about by its high pH, provides an environment which is conducive to pulp survival [12, 117]. Dentine bridges were still formed in a high percentage of cases when exposed pulps were purposely infected with bacteria prior to pulp capping with calcium hydroxide [107, 108]. This suggests that the bactericidal nature of calcium hydroxide is an important property of the material. As with HCSCs, it has been shown that calcium hydroxide can solubilize growth factors sequestered in dentine; this is thought to initiate the sequence of reparative events which leads to tertiary dentine formation [44].
Although numerous studies have demonstrated successful pulp healing with calcium hydroxide, many clinicians view its use in pulp capping with scepticism. A 5‐ and 10‐year retrospective analysis of 123 calcium hydroxide pulp‐capping procedures performed on carious exposures showed that 45% had failed in the 5‐year group and 80% in the 10‐year one [52]. In another retrospective analysis of 248 teeth, with follow‐up of 0.4–16.6 years (mean 6.1 ± 4.4 years), the overall survival rate was found to be 76.3% after 13.3 years [118]. Pulp capping in patients aged over 60 years showed a considerably less favourable outcome than in patients younger than 40 years.
All forms of calcium hydroxide, including the hard‐setting variants, are easily solubilized. This poses a challenge for long‐term restorative success, because even the best restorative materials available will inevitably undergo some form of microleakage. Under amalgam restorations, Dycal has been shown to be relatively soft in 70% of cases [119]; furthermore, it undergoes significant washout [120], so although it is bactericidal, it does not maintain a durable seal against bacterial microleakage [121].
2.4.3 Resin‐Based Adhesives
Resin‐based systems were first suggested for pulp capping in the mid‐1990s [122] and remained fashionable for the next 10–15 years. The initial interest came from non‐primate studies, which showed that mechanical exposures treated with adhesive systems led to pulp healing [123, 124]. Primate studies using uncontaminated mechanically‐induced exposures also showed positive results, demonstrating that resin‐based systems led to healing responses similar to those obtained with calcium hydroxide, the gold standard at the time [125, 126]. Further studies were conducted which reproduced more realistic conditions, such as capping of bacterial contaminated pulps. These represented the most common clinical situations, as most exposures result from a deep carious lesion or are treated when an operative field is not controlled with a rubber dam [127]. Between 2005 and 2008, seven human studies compared the histological response between resin‐based systems and calcium hydroxide, with between 16 and 40 teeth in each. All showed a more favourable response in the calcium hydroxide group compared to the resin‐based one irrespective of whether an etch‐and‐rinse or a self‐etch system was used [128].
Resin‐based adhesive systems are not suitable candidates for VPT due to their cytotoxic effects [129]; the challenge of obtaining a bacterial tight seal when there is likely to be moisture (open wound of the pulp), which will reduce polymerization [130]; the amount of unpolymerized material with a high prevalence of toxic components at the wound site; and certain components in 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