Introduction

Dental pulp tissue is a connective tissue found at the centre of the tooth, surrounded by dentine and enamel. When exposed through caries or tooth fractures, the dental pulp becomes highly susceptible to infections, which can lead to pain, necrosis, and severe infection of the alveolar bone and surrounding tissues (1). Currently, the most common treatment choice for pulp diseases in permanent teeth is orthograde root canal treatment (RCT), performed by a pulpectomy (complete removal of the damaged and healthy pulp inside the tooth), along with the possible use of dressing materials, filling with synthetic materials, and sealing to bring back masticatory function (2).

Vital pulp treatment (VPT) is a possible alternative to RCT, as it is a restorative dental procedure that aims to treat compromised dental pulp without completely removing the dental pulp tissue or excavating sound inner dentine walls (3). It can comprise indirect or direct pulp capping (applying a protective material that covers the pulp) and partial or complete/full pulpotomy (extirpation of part or all of the coronal pulp) (Figure 7.1A). It is more frequently performed in primary dentition (paediatric patients) due to incomplete root formation, ease of technique, and less trauma to young patients (7). Moreover, VPT is also indicated for secondary dentition (permanent), despite it not commonly being done for adults, precisely due to a lack of knowledge about the procedure and uncertainty regarding practitioners’ success rates (8).

Both VPT and RCT achieve similar high and predictable success rates when properly performed (9). However, the less invasive technique may be advantageous to patients with secondary dentition, as it may help to extend the survival of the teeth, as orthograde endodontically treated teeth can be at risk for structural failure during mastication. In addition, these teeth are biologically inferior, since root canal filling materials have no biological immune defence (higher risk of reinfection) and have no innervation, thus causing loss of sensation of environmental changes (possibly leading to more or worse caries), reinfection, and development of apical periodontitis (10).

Critical factors are important for a successful VPT, such as the amount of infected tissue, bleeding control and maintenance of pulp free of bacteria during the procedure, the patient’s age (since older patients have more fibrous pulp tissue and less blood supply), and healthy periodontium, in addition to the right selection of material for proper sealing and healing of the pulpal tissue and type of final restoration (3, 7, 11).

In this chapter, we will first describe native pulp conditions, its response to traumatic or carious injuries, and the decision‐making process that determines the best treatment approach. The concepts, standard materials (properties, advantages, and drawbacks), tissue response biology and clinical evidence of successful treatment will be deeply addressed in the second section. The bulk of this chapter will give special attention to existing and next‐generation regenerative‐based biomaterials to be employed in VPT, aiming at the outcome of regenerative endodontics outcome.

Native Pulp Conditions

Pulp tissue originates from the proliferation and condensation of neural crest cells (ectomesenchyme) that are prime to the development of the dental papilla, later originating in mature pulp tissue residing in an inflexible chamber made by dentine, enamel, and cementum (12). This tissue has a layer of highly specialized cells and odontoblasts along its periphery that continuously secrete dentine after development is complete, both under normal and non‐homeostatic conditions. In healthy pulp tissue, this dentine is called secondary and is slower‐paced and deposited circumferentially (in tubular continuity with primary dentine) at a gradual speed during the life of a vital tooth (12, 13).

Pulp tissue is a highly vascularized tissue. Usually, pulp microcirculation is nourished through dental arteries that come from the maxillary artery, a branch of the external carotid artery. This blood supply enters the tooth via the apical foramen, feeding each tooth (1). Overall, the pulp vessels are organized in a hierarchical system with arterioles in the central capillaries, and their branches at the periphery of the pulp, all with the same objective as any other circulatory flow in the human body, supplying the odontoblasts and other constituent cells with oxygen, as well as a source of nutrients (14). The venules are likewise present in the central part and are responsible for draining waste products (1). The dental pulp also provides robust mechanical support and protection from the microbial‐rich oral environment. Furthermore, this microcirculatory has an extraordinary incidence of innervation (mainly branches of the maxillary and mandibular divisions of the trigeminal nerve), which is involved in pulp pain perception and transduction, both of which are vital for warning of minimal changes from the healthy state (13) (Figure 7.1B).

Commonly, teeth with healthy pulp tissue have extra resistance to bacterial invasion into dentinal tubules compared to their endodontically treated counterparts, mainly due to the complex immune response and defence process evoked by resident cells. This cell complex combines to form a major robust immune cell population, namely, neutrophils, T lymphocytes, monocytes, dendritic cells, natural killer (NK) cells, B cells, and regulatory T cells (Tregs) (15). These immune cells are in homeostasis with adjacent odontoblasts, fibroblasts, and pulpal stem cells and are crucial for the immunological response when facing a microorganism attack (16).

These cells recognize potential threats via pattern‐recognition receptors (PRRs) that acknowledge pathogen‐associated molecular patterns (PAMPs) (17). The main PRRs are transmembrane receptors, referred to as toll‐like receptors (TLRs) (18). While not their main function, odontoblasts are immunocompetent cells expressing PRRs and represent the first defence response once they are in the vicinity of the pulp, with their cell bodies residing in the pulp chamber and their cellular processes extending into the dentinal tubules, thus being able to elicit an inflammatory response (19). TLR‐2 is activated by peptidoglycan, lipoteichoic acid (LTA), and lipoproteins, all of which are byproducts from gram‐positive bacteria predominantly found in carious lesions (20). Typically, gram‐positive bacteria dominate over gram‐negative bacteria in pulp tissue. Therefore, the TLR‐2 expression is initially more remarkable than TLR‐4 in dental pulp exposed to the oral environment (21) (Figure 7.1C).

Pulp Response to Traumatic or Carious Injuries

According to the last World Health Organization report, carious lesions are the most frequent non‐communicative disease, affecting almost half of the world’s population, leading to direct–indirect financial costs reaching US$442 billion in 2010 (22). The response of pulp tissue to irritation (regardless of traumatic or carious origin) is inflammation. If unattended, the integrity of the structural pulp environment will be lost, leading to exacerbated inflammation and pulp necrosis (23) (Figure 7.1D).

Since pulp is relatively incompressible, the total blood volume within the pulp chamber cannot be significantly increased. In this way, minor alterations in pulp microcirculation are the first to occur with the onset of pulp inflammation, leading to increased tissue pressure (1). Subsequent compression of the blood vessels contributes to the origination of pulp inflammation and necrosis, which may spread to the adjacent alveolar bone at a later stage and evoke periapical pathosis (24). In severe cases, pulp necrosis can culminate in oral sepsis, which can be life‐threatening if the infection spreads, causing purulent sinusitis, meningitis, and brain abscess from the maxillary teeth, or Ludwig’s angina from the mandibular teeth (25).

In carious lesions, changes in the odontoblast cell layer occur even before the pulp tissue appears inflamed. As mentioned earlier, the odontoblasts and undifferentiated mesenchymal cells (which may differentiate into dentine‐forming cells if stimulated) hold the capacity to form dentine throughout life, enabling pulp to compensate for the loss of enamel or dentine caused by caries, called tertiary dentine (1, 13). This tertiary dentine can be termed reactionary dentine (secreted by surviving post‐mitotic odontoblasts) and reparative dentine (secreted by a new group of odontoblast‐like cells derived from a progenitor cell population) in reaction to adverse stimuli, such as caries or operative procedures (detailed in Chapter 2). The rate seems to depend inversely on the rate of carious attack; that is, more dentine is formed in response to slowly progressing carious lesions (23).

During infections with gram‐negative bacteria, PAMP lipopolysaccharide (LPS) represents the main byproduct released by bacteria and can produce inflammation (26). When bound to TLR‐4, it evokes an activation of the inflammatory molecular cascade through the nuclear factor‐kappa B pathway (NF‐Kb), releasing several proinflammatory cytokines, such as interleukin IL‐1 beta and tumour necrosis factor‐alpha (TNF‐a), which mediate innate immune responses by regulating phagocytosis and triggering antimicrobial activity (15). Chemokines recruit and activate tissue‐resident and blood‐borne immune/inflammatory cells at the site. As microorganisms keep invading the pulp, destruction of the odontoblast layer is observed, and the subjacent pulp fibroblasts are triggered to participate in the host response, similar to odontoblasts through TLRs (27). If not properly addressed, long‐term irritation will cause chronic pulp inflammation, which further culminates in total pulp necrosis that will then be followed by infection of the periradicular space, since bacteria will have a pathway by which it can enter the area via foramen (24).

Similar to carious lesions, traumatic dental injuries (TDI) are another concern regarding dental pulp response, since they are also very frequent, with one in four individuals aged 6–50 years having evidence of TDI, according to a U.S. national survey (28). Mild injuries, such as enamel cracks or minor uncomplicated crown fractures, may cause mild localized inflammation in the pulp, which usually resolves by itself through continuous dentinal tubule deposition (29). On the other hand, in complicated crown fractures, the pulp is lacerated and exposed to the oral environment (30, 31). Unless the tooth is quickly restored, this will evoke localized haemorrhaging, bacteria and toxins penetrating the tissue, leading to liquefaction‐type necrosis, similar to that seen following carious exposure (29).

Trauma causing the displacement of teeth from the alveolus will result in damage to the apical blood vessels. When affecting fully developed teeth, these blood vessels will not be able to heal and revascularize the pulp (29). Nevertheless, a young tooth with a wide root apical foramen probably will recover and re‐establish blood flow (32). In aseptic necrotic pulp tissue, if the tooth remains intact, the necrotic pulp may remain sterile and poses no adverse effects on the surrounding periradicular tissues. However, due to the lack of blood supply and a competent immune system defending it, a secondary crack or fracture may provide a pathway for bacterial entry that will easily infect the root canal system and result in periapical and periodontal pathologies (24, 33).

Decision‐making for Pulp Exposures

It is believed that several tooth extractions could be avoided if proper treatment was carried out at the first diagnostic appointment (34). However, due to the difficulty in identifying unclear symptoms and the inaccessibility of the pulp for clinical tests, the right diagnosis becomes difficult (35). Moreover, the presence of a referred toothache derived from tissues other than pulp hampers accurate identification. In this way, the professional should conduct an appropriate clinical examination and diagnostic tests.

As outlined in Chapter 3, pulpal diagnosis is based on the patient’s pain history. Second, sensibility tests, such as applying cold, hot, and electric stimulus, provides the clinician with additional evidence to assist with diagnosis. In addition to such tests, percussion tests may infer a pulpal state from the presence of symptomatic apical periodontitis (36, 37). When there is a possibility of seeing pulp tissue, complete caries removal is indispensable to eliminating infected tissues and creating appropriate conditions to visualize the pulp tissue underneath, according to the American Association of Endodontists (AAE) (7, 38). However, a recent position statement by the European Society of Endodontology (ESE) recommended that selective carious‐tissue removal is advocated (39). A lack of consensus among the experts regarding caries removal and how to manage deep caries is an evolving topic that forces new studies. Finally, intraoral radiographs evaluate the extent of root formation and apical foramen width (40).

Regarding signs and symptoms, spontaneous unprovoked pain, sinus tract, excessive mobility not associated with trauma, apical radiolucency, and radiographic evidence of internal or external resorption have a clinical diagnosis of irreversible pulpitis or necrosis, making them suitable candidates for RCT. On the other hand, induced or short‐duration pain that ceases upon removal of the stimulus has a clinical diagnosis of reversible pulpitis and is eligible for VPT (7).

Since the primary goal of VPT is to create conditions for pulp tissue preservation and repair, the amount of remaining pulp tissue after disinfection must be based on operator evaluations, the overall treatment plan, and the patient’s general oral and systemic health to allow for healing (41). The age of the patient is directly correlated with the pulp tissue’s volume, since continuous deposition of secondary dentine throughout one’s whole life leads to pulp recession and difficulty with execution of the VPT but does not affect outcomes when properly conducted (13, 42, 43). In addition to pulp volume, the patient’s age also interferes with the level of root development and apical foramen diameter, where incompletely developed roots and open apex enhance the chances of a successful VPT (13, 29).

Also, the timeframe between pulp exposure to the oral environment and treatment is a determinant in deciding between RCT and VPT, as well as the location of the injury and how it happened (32). A delay in initiating endodontic treatment after a trauma incident in a contaminated environment increases the chances of the pulp becoming necrotic and unsuitable for VPT (32). Furthermore, the patient’s ability to return for follow‐up appointments should also be considered, since VPT requires numerous radiographs over the following year to assess the success of the technique (28).

Overall, many aspects should be considered quickly in order to apply the right pulp treatment. When the treatment plan is established, other considerations should be properly made, as in the case of materials selection for each case, which will be discussed in the following sections.

Historical Background on VPT Materials and Their Influence on Success

As discussed above, bacterial invasion caused by caries and dental trauma affects dental pulp and can lead to inflammation that, if left untreated, results in pulp necrosis (44–46). These damages imply the need for a variety of further treatments, depending on the injury’s severity and timeframe. The materials used for vital pulp therapy in permanent teeth have evolved over time. The first materials used in VPT were likely basic materials, such as calcium hydroxide (Ca(OH)₂) and formocresol.

Formocresol, a mixture of formaldehyde, cresol and glycerin, was first introduced in the 1930s and was widely used for many years as a pulp therapy material. It has been shown to have strong antimicrobial properties, as well as the ability to fix tissue; however, due to concerns about its toxicity, formocresol has largely been replaced by other materials.

Calcium hydroxide has been used in dentistry as a pulp‐capping material for over a century; it has been considered the gold standard for a long time and may still be effective in certain situations (41). Calcium hydroxide has been shown to have excellent antibacterial properties and, when applied to pulp tissue, stimulates the formation of a mineralized tissue barrier that helps to protect the pulp from further damage. Calcium hydroxide materials are commercially available as a powder or paste, according to their intended use. For indirect pulp capping, it is conventionally presented as a two‐paste material that is mixed and applied as a liner on the internal walls of the cavity. In the meantime, direct pulp capping using Ca(OH)₂ is often applied as a pristine powder directly onto the exposed area. Due to its high alkalinity (pH ~12.5–12.8), Ca(OH)₂ creates a critical environment for bacteria, and the hydroxyl ions induce phospholipid membrane disruption that leads to bacterial death (47). In conjunction with this, due to the high pH of Ca(OH)₂, its direct contact with pulp or through micro exposures in indirect pulp capping induces an inflammatory response that acts as a signalling stimulus for dentine matrix secretion at the region of the injury (48). Furthermore, Ca(OH)₂ products also result in partial solubilization on the dentine matrix that releases bioactive molecules and consequent dental pulp stem cells (DPSCs) recruitment to the area of the damage (49). In the meantime, calcium and hydroxyl dissociate in contact with aqueous fluids and play pivotal roles in mineral deposition to form mineralized barriers (Figure 7.2C).

Despite its good properties, there are several disadvantages to using Ca(OH)₂, such as limited sealing ability – Ca(OH)₂ has a limited ability to seal the pulp and may allow bacteria to penetrate the pulp tissue, leading to further infection and inflammation; poor mechanical properties – Ca(OH)₂ is a weak material and can be easily displaced or washed out of the tooth during the procedure, thus reducing its effectiveness; long‐term success rate – studies have shown that the long‐term success rate of pulp capping and pulpotomy procedures using Ca(OH)₂ is lower than those using mineral trioxide aggregate (MTA) or other newer materials. Moreover, Ca(OH)₂