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.