2.2.1 Why Maintain the Pulp?

Maintaining healthy pulp tissue is preferable to root canal treatment (RCT), which can be complex, destructive, time‐consuming, and expensive for both patients and clinicians. Preserving all or at least part of the dental pulp is important after pulp exposure, especially when the tooth is immature and root formation is not yet complete [1]. The need for a more conservative approach to management of the inflamed pulp is a more biologically based and minimally invasive treatment strategy compared with pulpectomy and has recently been encouraged in editorials and position statements [1, 2]. Besides reducing intervention, this biological concept also maintains pulp developmental, defensive, and proprioceptive functions [3, 4]; VPT is generally considered technically easier to execute than RCT [5]. From a longitudinal perspective, advocating less aggressive dentistry reduces overtreatment and limits the ‘restorative cycle’ concept [6], whilst also improving the cost‐effectiveness of treatment [7]. Finally, with the surge in research and interest in regenerative endodontics [8], biomaterial developments [9], and the need to therapeutically utilize dental pulp stem cell (DPSC) populations [10], VPT has reemerged as an area of significant interest to both patients and dentists [11].

2.2.2 Pulpal Irritants

Although the pulp can be challenged by microbial, mechanical, and chemical stimuli, necrosis will not result without the presence of microorganisms [12]. Caries has traditionally been considered the principal cause of pulpal damage, and although falling in prevalence, it is now manifesting more commonly in disadvantaged and elderly populations [13–15]. Whilst inflammation of the pulp is evident even in shallow carious lesions [16, 17], it is not until the carious process is deep and comes within 0.5 mm of the pulp that the pulpitic response significantly intensifies [18]. As a result, before it reaches this stage, the damage is likely to be reversible. This forms the basis of predictable operative dentistry, in that the pulp should recover after removal of carious dentine and insertion of a suitable dental restorative material [19]. Microbial challenge, however, is not limited to caries, as bacterial microleakage is also a common cause of pulpitis and subsequent necrosis due to oral microorganisms colonizing the ‘gap’ between the restoration and the tooth [20]. Prevention of microleakage using lining material is no longer considered good practice [21], but dentine bonding agents and incremental placement of resin‐based composites will reduce the risk of bacterial colonization [22], particularly if there is sufficient residual dentine thickness (RDT).

Views on the irritant effect of dental materials on the pulp have changed over the last 50 years. The idea that their toxicity to pulp tissue leads to pulpal necrosis has been questioned by several operators [20, 23, 24], who point to microbial contamination and leakage as the decisive factor in sustained pulpal inflammation. That said, there is also good evidence to suggest that some materials are more biocompatible and ‘pulp‐friendly’ than others, with the adverse toxic effects of dental resins on pulp cells being repeatedly highlighted [25, 26]. Alternatively, the positive biological responses of HCSC [9] have led to recent suggestions that deep carious lesions should be lined with HCSC after deep caries removal [27]. Other nonmicrobial irritants such as bleaching procedures, particularly chairside ‘power’ techniques, can lead to rises in pulpal temperature and pulpitis [28]; however, whilst these are increasingly common as treatment strategies, the pulpal changes seen are generally reversible and are not catastrophic in nature [29, 30].

2.2.3 Pulpal Healing After Exposure

The odontoblast cell is responsible for forming primary dentine during tooth development, the more slowly deposited secondary dentine throughout the life of the tooth, and, when ‘irritated’, tertiary dentine in the pulp tissue adjacent to the source of challenge [31]. Dependent on the stimulant severity, tertiary dentine deposition can be either reactionary or reparative (Figure 2.1) [32]. Reactionary dentine is formed by an upregulation of existing odontoblast activity when the dentine–pulp complex is exposed to a relatively mild stimulus (e.g. shallow or slowly progressing carious disease process), whilst reparative dentine is formed generally after a stronger stimulus has led to odontoblast cell death (e.g. deep caries or traumatic exposure) [32, 33]. At a cellular level, reparative dentine is believed to be produced following cytodifferentiation of pulpal progenitor cells (DSPCs or other progenitor cells) and the formation of a new generation of odontoblast‐like cells [1, 32, 33]. Although this description of reparative dentinogenesis represents the currently accepted theory, others have highlighted the influence of other cells such as fibroblasts or fibrocytes as secretory cells [34, 35]. The cellular differentiation is guided by the influence of growth factors and other bioactive molecules released from both the dentine matrix and the pulp cells themselves [36, 37]. Whilst for didactic purposes the processes of reactionary and reparative dentinogenesis are considered separately in the event of pulp exposure, both are likely to occur simultaneously [38].

Inflammation is also an important stimulus that drives the reparative process [39], with odontoblasts involved in initial sensory stimulus transmission from the dentine and possessing an immunocompetent role in cellular defence [40]. Indeed, the low‐level release of inflammatory mediators such as interleukins‐2 and ‐6 in mineralizing cells in contact with an HCSC such as mineral trioxide aggregate (MTA) supports the need for a degree of inflammation in promoting regenerative processes [41].

A wide range of bioactive dentine matrix components are ‘fossilized’ in the mineralized tissue and released into the pulp during caries or trauma [38, 42]. Demineralization of dentine, and indeed contact with materials such as MTA [43], calcium hydroxide [44], and other agents [45], releases a plethora of bioactive molecules, including members of the transforming growth factor‐β (TGF‐β1) superfamily, which can stimulate a complex cascade of molecular events that promote pulp repair [36, 44]. These materials liberate dentine matrix components to varying degrees, highlighting the influence of the material in the biological response [46].

Using biologically based dental materials that promote the healing process is paramount in VPT [47]. Other strategies using irrigants to enhance the release of bioactive molecules from dentine in order to improve wound repair are also being developed [48]. Over the last 10 years, HCSCs have shown superior histological response compared with the gold‐standard material, calcium hydroxide, in VPT [9, 49]. HCSCs work in a similar way to calcium hydroxide but are more efficient in their interaction with dental pulp cells and dentine extracellular matrix (dECM) [50]. In reality, both their mechanisms of action remain nonspecific and untargeted in nature (Figure 2.1) [49, 51].

2.2.4 Classifications of Pulpitis and Assessing the Inflammatory State of the Pulp

An accurate assessment of the inflammatory condition of the pulp has a large bearing on the success of VPT procedures, as teeth with carious exposures have a poorer outcome than those with traumatic ones [52, 53]. Pulpitis is generally classified as being either reversible or irreversible [54, 55]; however, in light of the development of predictable VPT solutions, such as pulpotomy in teeth with signs and symptoms indicative of irreversible pulpitis, alternative classifications have been proposed in order to more accurately reflect the true state of the pulp [2, 27]. New classification systems have tried to link diagnosis and management and to use more descriptive terms including ‘mild’, ‘moderate’, and ‘severe’ pulpitis [2], but their usefulness in effectively replacing the current classification system remains speculative. Pulpal status is routinely determined after pain history, a clinical/radiographic examination, and pulp tests. Unfortunately, clinical signs, symptoms, and tests are relatively nonspecific and generally do not accurately reflect the histopathological status of the pulp [56, 57] – although this assertion has recently been queried, as a strong correlation between pulp histology and the signs and symptoms of reversible and irreversible pulpitis has been demonstrated [34].

Reversible pulpitis can present either with no patient complaint or with symptoms that can extend to a sharp pain sensation with thermal stimuli. Notably, the pain resolves rapidly once the stimulus is removed. Spontaneous pain and sleep disturbance tend to indicate irreversible pulpitis [1, 57], with the symptoms lingering after stimulus removal. Unfortunately, patient symptoms are at best a guideline and can even mislead the clinician, with irreversible pulpitis being symptomless in the majority of cases [54, 58]. During the early stages, teeth presenting with signs and symptoms of irreversible pulpitis usually exhibit significant pulpal damage only in the area of the coronal pulp under the carious lesion, with a largely uninflamed radicular pulp [1, 34]. Invariably, without intervention, the partial irreversible pulpitis will progress until the entire pulp is irreversibly inflamed and necrosis ensues. Although treatment decisions are largely based on patient signs and symptoms, current tools are insufficient to accurately determine the threshold between reversible and irreversible forms [59]. As a result, it is critical to identify more discriminative tests based on molecular analysis of pulpal biomarkers [1].

2.2.5 Is Pulpal Exposure a Negative Prognostic Factor?

A traumatic pulpal exposure in a mature tooth, treated by pulp capping or pulpotomy, is a predictable procedure with a similar prognosis to RCT of >90% success [60, 61]. By contrast, if the pulp is cariously exposed, it has by its very nature been subjected to a sustained bacterial onslaught for a considerable period of time; this reduces the predictability of the VPT procedure, with quoted success rates ranging from as low as 20% [52, 62] to over 80% [11, 63]. The wide range of success highlights the difficulties in treating carious exposures and comparing individual pulp‐capping studies, which show heterogeneous data, with some defining patient symptoms and pulpal diagnosis [11] and others including a mixed sample of both carious and traumatic exposures [64].

Although there is general agreement when managing deep lesions that the margins of the cavity should be clear of caries, there is less concurrence over whether all carious dentine overlying the pulp should be removed [63, 65]. In a tooth with a deep carious lesion which responds within normal limits to sensibility testing, selective (or partial) caries removal and avoidance of pulp exposure is recommended in preference to nonselective (or complete) removal and subsequent risk of exposure [1, 62, 66, 67]. This management strategy for deep caries can be carried out in one visit as indirect pulp therapy, or in two as a stepwise excavation technique [21]. There are a small number randomized controlled trials investigating caries management strategies in permanent teeth, but recent five‐year results of a previously published trial [66] showed that selective (partial) caries removal and stepwise excavation increased the number of teeth that remained vital compared with a nonselective (complete) removal technique [62]. However, this assumes that pulp exposure is the principal problem, which is not convincingly shown in either study [62, 66]. Other conflicting prospective studies have demonstrated opposing results, with high success rates for conservative treatment of the cariously exposed pulp in an endodontic practice setting [63], general practice setting [68], and university setting investigating teeth with signs and symptoms of irreversible pulpitis [11]. All these studies used HCSCs such as MTA and Biodentine, but notably were not randomized in design.

At present, it appears that careful aseptic handling of the pulp tissue under magnification, judicious removal of pulpal tissue, and appropriate restoration of the tooth exposure may produce results comparable with or better than RCT [62, 63, 69].

2.2.6 Soft Tissue Factors Unique to the Tooth

Inflammation is a response to injury, and the presence of polymorphonuclear leucocytes and chronic inflammatory cells is indicative of failure of VPT. Swelling is also a feature of the inflammatory response, but the unique anatomy of the dentine–pulp complex and the rigidity of the surrounding dentine prevent expansion of the pulp. Additionally, after pulpal exposure, the buffering effect of the dentine is lost and the pulp tissue is rendered sensitive to potential adverse interactions from materials or microbes [70]. Notably, inflammation is also important in driving the soft tissue response during healing following placement of a pulp‐capping material [39]. Calcium hydroxide produces a mild irritation of the pulp and stimulates repair. If pulp capping is successful, then after a few days there will be a reduction in the number of inflammatory cells present under the necrotic zone, whilst under the capping material, the pulpal cells will proliferate, migrate, and form new collagen in contact with the necrotic zone [71]. Although the process is similar with HCSC, the pulpal irritation is less than that with calcium hydroxide (Figure 2.2) [9]. Tertiary reparative dentinogenesis is then initiated, odontoblast cells are formed, and mineralized matrix is secreted [72]. This matrix forms the so called ‘hard tissue’ bridge, which walls off the pulp and offers further protection to the soft tissue adjacent to the wound site.

2.3.1 Managing the Unexposed Pulp

Regardless of the many years spent researching the ideal restorative material, there is no such thing as a permanent restoration: all have a limited lifetime [73]. As soon as the integrity of a tooth is broken, it must be replaced, setting it on a ‘restorative cycle’ [74]. And each time a restoration is placed, the pulp is made vulnerable and put under threat.

Clinicians carrying out an operative procedure on a vitaI tooth should be mindful of the heat generated by dental handpieces, the potential damage caused by overdehydrating dentine, and the use of caustic agents in tooth restoration, all of which can result in unnecessary iatrogenic pulp damage. Often, prevention is better than cure, so care and attention should be taken when removing tooth tissue and selecting materials to prevent injury to the pulp. The most influential variables in terms of causing injury to the unexposed pulp are considered the cavity’s RDT and preparation of the cavity in the absence of coolant [75]. This confirms the observation that excessive heat is the most injurious event to pulp tissue [76]. Other potential sources of pulp injury during restoration of a cavity include etching of the dentin [77] and the choice of restorative material [78].

Any therapeutic process for the benefit of pulp survival that is adopted during the restoration of a tooth with a deep cavity, but unexposed pulp is an indirect pulp cap. Classically, this procedure is carried out when dentine is lost due to caries, trauma, or a previous iatrogenic intervention, and when a cavity exists close to the pulp but dentine remains over the pulp tissue. Indirect pulp capping can be defined as an application of a material on to a thin layer of dentine located close to the pulp with the aim of producing a positive biological response so that the pulp can protect itself.

2.3.2 Tooth Preparation to Avoid Exposure

The tooth should be isolated with a rubber dam and asepsis should be maintained throughout cavity preparation. The cavity should be disinfected using cotton pellets soaked with sodium hypochlorite (0.5–5%). Less invasive carious tissue‐removal techniques are generally carried out using sterile round burs and excavators [79], but other self‐limiting chemomechanical methods (e.g. Carisolv gel) have also been advocated for the management of deep carious lesions [80]. Regardless of the technique employed, carious tissue should be removed from the periphery of the cavity to hard dentine (i.e. nonselective removal), leaving soft or leathery dentine only on the pulpal aspect of the cavity. As RDT over the pulp cannot be accurately assessed clinically, the use of a biologically based biomaterial is recommended. Ideally, an HCSC or a glass ionomer cement (GIC) should be routinely applied to the dentine barrier prior to definitive restoration (Figure 2.3) [1, 27].

2.3.3 Managing the Exposed Pulp

If there is a suspicion that the pulp is exposed, the tooth should be immediately isolated with a rubber dam to ensure an aseptic environment and prevent any of the consequences that would result if the pulp were to become infected [12]. Magnification should ideally be used throughout the procedure to ensure removal of all softened dentine and to allow visual inspection of the pulp tissue in order to determine the degree of inflammation. The dentine should be carefully manipulated using sterile burs and sharp instruments. A high‐speed bur and water coolant should be used for pulp tissue removal [81], followed by disinfection and control of pulpal bleeding. Haemostasis and disinfection should be achieved using cotton pellets soaked ideally with sodium hypochlorite (0.5–5%) or chlorhexidine (0.2–2%) [64, 82, 83]. If haemostasis cannot be controlled after five minutes, further pulp tissue should be removed (partial or full pulpotomy). In cases with signs and symptoms indicative of irreversible pulpitis (i.e. partial irreversible pulpitis confined to the coronal pulp tissue), a full coronal pulpotomy can be carried out to the level of the root canal orifices, with bleeding arrested as detailed previously [84]. This procedure may be easier for general dental practitioners without access to magnification than either partial pulpotomy or even direct pulp capping. Ideally, an HCSC should be placed directly on to the pulp tissue and the tooth immediately definitively restored to prevent further microleakage [61, 83, 85]. If bleeding cannot be controlled after full pulpotomy, a pulpectomy and RCT should be carried out, provided the tooth is restorable. Four different VPTs can be carried out: direct pulp capping, partial pulpotomy, full pulpotomy, and pulpectomy.

2.3.3.3 Full Pulpotomy

This procedure is carried out when there is gross loss of dentine due to caries, trauma, or previous iatrogenic intervention and a cavity exists where a large portion of the soft tissue of the pulp is exposed and bleeding, suggesting inflammation or contamination, or where it is not possible to obtain haemostasis at a superficial level. Full pulpotomy is defined as complete removal of the coronal pulp to the root canal orifice level, followed by application of a material directly on to the remaining pulp with the aim of producing a positive biological response so that the pulp can protect itself (Figure 2.6).

2.3.3.4 Pulpectomy

For completeness, this procedure is considered here as it is a form of VPT. In treating cases where it is determined that the pulp is not viable as it appears to be severely inflamed or contaminated and haemostasis is unachievable or the pulp appears necrotic, a pulpectomy may be indicated. It has been shown that success rates are higher when the pulpectomy and RCT are completed in one visit, and the clinician should adopt a cautious approach with length control. Pulpectomy is defined as total removal of the pulp from the root canal system followed by RCT (Figure 2.7).

2.3.4 Immature Roots

VPT is of particular importance in immature permanent teeth where root formation is not complete and the root structure is weak. Successful maintenance of pulp vitality will allow root formation to continue in a process known as apexogenesis. In reality, the term ‘apexogenesis’ is seldom used in modern endodontics, first because it is often confused with apexification, and second because it simply refers to pulp capping: a partial or full pulpotomy procedure carried out in a tooth with an immature root structure. VPT on immature teeth is most commonly carried out following trauma on the anterior teeth, which for practical reasons may be better treated with a partial or ‘Cvek’ pulpotomy, where part of the exposed pulp tissue is removed and a capping material is placed [60]. Young patients presenting with an open apex will have a greater blood supply and increased cellularity of their pulps, which has been suggested to result in more predictable healing [86]. However, the influence of age has not generally been linked to improved healing in VPT [64, 87].

2.4.1 The Role of the Material

For predictable and successful VPT, careful material selection is required. The demands on the material itself are numerous, as it is situated in a unique environment in which it must interface with vital tissue that has a blood supply, hard dental tissues, and other restorative materials. Historically, numerous different materials have been used in VPT, including gold foil [88], aqueous calcium hydroxide [89], commercial preparations of calcium hydroxide [90], glycyrrhetinic acid/antibiotic mixture [91], resin bonding agents [92], corticosteroid/antibiotic mixture [93], isobutyl cyanoacrylate [94], resin‐modified glass ionomer [95], and, more recently, HCSC [96].

The fundamental aim of any material used in VPT is to maintain a viable pulp so that it can continue normal homeostatic and protective functions of the tooth. As the pulp has the ability to lay down dental hard tissue in the form of reactionary or reparative dentine, the chosen material should promote this response in order to increase the thickness of dentine between the pulp and the deepest part of any cavity (Figure 2.2). The production of a thicker layer of mineralized tissue over the pulp renders it well protected from future noxious stimuli. Any pulp‐capping material should also have antimicrobial properties, as it is well established that pulp necrosis will not result without the presence of microorganisms [12].

Materials used in VPT should have the following characteristics:

• Antimicrobial activity
• Creation of a bacterial tight seal and prevention of microleakage
• Promotion of tertiary dentinogenesis and control of hard tissue barrier formation
• Biocompatibility (prevention of ‘over’‐irritation and avoidance of induction of a severe inflammatory response
• Radiopacity
• Clinical ease of handling
• Resistant to forces of displacement following the subsequent application of a further material over the agent used in VPT
• Lack of induction of tooth discolouration

No one material demonstrates all of 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]