Summary

Revitalization or regenerative endodontic procedures in immature teeth with necrotic pulps are now part of the therapeutic endodontic spectrum and should be considered as an alternative treatment to mineral trioxide aggregate (MTA) apexification. Evidence from clinical as well as laboratory studies has led to the publication of recommendations from several endodontic societies. In contrast to MTA apexification, revitalization may support healing of apical periodontitis after induction of a blood clot inside the root canal to generate a biological ‘root filling’. Whereas previous expectations of true pulp regeneration have to be reconsidered, revitalization procedures still offer benefits for the patient. Besides the resolution of pain and inflammation, the formation of an immunocompetent tissue inside the root canal with potential mineralization capacities might at least partially reconstitute the biological structures and functions of pulp tissue. The procedural details regarding instrumentation, disinfection, and the use of various materials during the procedure might have a greater impact on outcome compared to conventional root canal treatment, as revitalization requires a thorough understanding of its biological basis. In terms of the future, revitalization is an interesting approach because it capitalises on tissue responses and healing capacities, and new insights from this treatment might take us a step closer to the goal of true dental pulp regeneration.

29.1 Regeneration and Repair Processes in the Dental Pulp

It has been known for decades that the dental pulp possesses considerable regenerative and reparative capacity, and the use of agents such as calcium hydroxide to promote healing after pulp capping procedures goes back nearly 100 years [1]. The main threat to pulp tissue is infection with oral bacteria through carious lesions, where bacterial components and eventually bacteria themselves and their toxins reach the pulp via dentinal tubules. The first target for external stimuli is the odontoblasts because of their localization at the dentine-pulp interface. Microbial components activate an innate immune response, which mobilises a variety of protective measures, including the reactions of odontoblasts, the production of neuropeptides, the activation of immune cells, and the production of chemokines and cytokines [2]. Once the bacterial front has progressed and odontoblasts have perished, pulp fibroblasts are actively involved in the immune response. It has been shown that these cells are capable of producing complement factors and thus actively eliminate bacteria via the membrane-attack complex [3]. The cell types that contribute to regeneration and repair include odontoblasts, pulp fibroblasts, neurons, and immune cells, in addition to pulpal stem cells. They are involved during regular tissue turnover to replace aged cells, but specifically during repair and regeneration. An insult recruits these cells, located in the perivascular niche [4], to the site of injury via chemotactic signaling; then they migrate and differentiate into secondary odontoblasts [5].

Regeneration, which restores the physiological structure and function of a tissue, might take place in the case of mild inflammation and if therapeutic intervention occurs early. In that case, the odontoblasts can increase their secretory activity, produce tubular dentine, and the inflammation can resolve fully. However, in most cases, repair will take place, where ectopic tissue formation leads to healing. Repair in the dental pulp involves the deposition of an amorphous mineralised tissue and replacement of odontoblasts by cells such as secondary odontoblasts or fibroblasts [6].

Several clinical strategies aim to regenerate or repair the dentine-pulp complex, depending on the stage of inflammation and tissue damage. Selective caries removal, pulp capping, and pulpotomy can maintain vital pulp tissue. Historically, pulp necrosis has been treated by root canal treatment (RCT), where tissue function is lost and the pulp chamber and root canal spaces are filled with synthetic materials. Novel therapies such as revitalization have emerged, which target new tissue formation inside the root canal. After provoking bleeding into the canal, the blood clot can serve as a scaffold and the origin of healing and repair. In this scenario, various cell types enter, vasculature and innervation are re-established, and the generation of extracellular matrix, in addition to minerals, lead to the development of new tissue, such as fibrous tissue, cementum, or bone [7–9].

29.2 Revitalization – Terminological Aspects

In the first case report that described an endodontic procedure to maintain or regenerate pulp-like tissue in an immature tooth, the approach was referred to as ‘revascularization’ [10]. The term was adapted from dental traumatology, based on the knowledge that the blood supply in teeth with open apices can re-establish after replantation of avulsed teeth, leading to a completion of root formation. More case reports, then case series, were published using this term. The first clinical report, which sparked further attempts at regenerative endodontic treatment in immature teeth was published by Banchs and Trope [11]. The mandibular premolar they described completed root formation after disinfection, provocation of bleeding into the canal, application of mineral trioxide aggregate onto the clot and an adhesive restoration [11]. This report caught the attention of the endodontic community, and the expectation arose that this treatment approach provided the means to regenerate dental pulp based on the observation that immature teeth were associated with completion of root formation after this procedure. The term ‘regenerative endodontic procedures (REPs)’ was coined to more broadly describe ‘biologically-based procedures designed to replace damaged structures, including dentine and root structures, as well as cells of the pulp-dentine complex’ [12]. As the procedure was established for immature teeth with pulp necrosis, more teeth were treated using REPs with the induction of a blood clot, where the main cause of pulp necrosis was dental trauma. Root lengthening and thickening was observed infrequently and not predictably in these cases, which was later verified in a clinical study [13]. The term ‘revitalization’ appeared in case reports, taking into consideration that the tissue that forms inside a root canal is an ectopic tissue. Histological studies both in animals and extracted teeth from patients which had received REPs provided evidence that the new tissue contained elements of pulp tissue (fibroblasts, connective tissue, blood vessels, collagen), but other cell types were missing (odontoblasts) and nontargeted cell types or tissue were often present such as osteoblasts and cementum [7, 8, 14]. The tissues found in those reports imply that what mostly takes place may not be regeneration but healing or repair, which is defined as tissue formation with a (partial) loss of function of the original tissue. This was taken into consideration, and according to the terminology in periodontology, the term ‘guided endodontic repair’ was suggested [15]. To date, data support the concept that new pulp tissue formation can only take place if remnants of the original pulp remain, as is often the case in the specific situation of a dens evaginatus, which was also the reason for the periradicular lesion in the case report presented by Banchs and Trope [11].

29.3 Position Statements of the ESE and AAE

The American Association of Endodontists (AAE) issued recommendations on the indication and procedural details for REPs in 2013. In the AAE position statement, regenerative endodontics was described as part of the endodontic treatment spectrum and described as ‘one of the most exciting new developments in dentistry today’ [16]. The AAE published treatment considerations based on a review of case studies in 2013; the document was last updated in April 2018 and is available from the AAE website However, the AAE calls upon practitioners using this protocol to actively research new findings given the evolving nature of this field.

The European Society of Endodontology (ESE) published a Position Statement on Revitalization Procedures in 2016 [17]. The document contains background information, the description of indication, guidelines for clinical assessment, and procedural details as well as information on follow-up, potential complications, and expected outcome. This document also states that ‘As … new evidence is still emerging, this position statement will be updated at appropriate intervals. This might lead to changes to the protocol provided here’ [17].

29.4 Case Selection, Indications, and Contra-indications

Revitalization is indicated in immature teeth with pulp necrosis, with and without the presence of periapical lesions. It is thus an alternative to an apical plug or barrier with hydraulic calcium silicate cements. The choice of treatment has to be made on an individual basis. It has been suggested that revitalization is preferred in cases with early stages of root development 1 to 3 according to the classification of Cvek [18] (less than half to over two thirds of root development with open apex); at stage 4 (nearly completed root formation with open apex), revitalization or an MTA plug can be performed [19]. The causes that account for the consideration of revitalization are mostly trauma and less frequently caries or pulpal infections due to developmental aberrations (dens evaginatus, dens invaginatus).

Prior to treatment, the patient and parents or legal guardians need to be given comprehensive information regarding the problem, revitalization and alternative treatment options, the aim of the treatment, steps of the procedure, the expected outcome, and the necessity for regular follow-up.

Allergies to the medicaments and agents used during the procedure need to be precluded. Contraindications include avulsed teeth immediately after replantation (as revitalisation may occur naturally), impossibility of adequate field isolation, and teeth that require restoration with a post. Medically compromised patients (American Society of Anaesthesiologists [ASA] physical status classification class III and higher) may rather receive conventional treatment [17], but it has to be noted that this is not evidence but rather consensus-based.

Revitalization is technically easier to perform compared to an apical plug; it is furthermore less invasive because a synthetic material is not placed in direct contact with the periapical tissues but in the coronal third of the root, allowing for a ‘biological root canal filling’. The procedure can be accomplished with currently available endodontic instruments, irrigants, medicaments, and materials. However, patient compliance is an important factor; in particular, the provocation of bleeding may cause discomfort. It should be considered that procedural details may not be the only decisive factor, but rather the clinician’s thorough understanding of the responses of cells and tissues targeted with this biology-based treatment.

29.5 Clinical Procedure

After proper clinical diagnostics and case selection, the procedure during the first visit includes:

• field isolation,
• the preparation of an access cavity,
• disinfection and irrigation of the root canal with 1.5 to 3% sodium hypochlorite (NaOCl) without or with minimal filing of the canal walls,
• the placement of calcium hydroxide as an intracanal medicament and a sound restoration.

A thorough clinical assessment is carried out during the next visit, and signs and symptoms of inflammation should have receded before the next steps are carried out:

• optional: anaesthesia (possibly without vasoconstrictor),
• field isolation, access cavity preparation,
• rinse with 17% Ethylenediaminetetraacetic acid (EDTA) and remove excess liquid with paper points,
• induce bleeding by mechanical irritation of the periapical tissues until blood approaches approximately 2–3 mm apical to the cemento-enamel junction,
• optional: place a collagenous material, which can facilitate the placement of a hydraulic calcium silicate cement in direct contact with the blood clot [20, 21],
• restore with a dentine bonding agent and resin composite to prevent access of bacteria.

A summary of the critical steps is shown in Figure 29.1; images of the clinical procedure are presented in Figure 29.2. Regular follow-up is recommended. Particular care needs to be given to the following issues.

29.5.1 Disinfection

As for conventional root canal treatment, removal of necrotic tissue and sufficient disinfection are critical in the context of revitalization. Mechanical instrumentation to remove infected dentine is not recommended due to the potential additional weakening of fragile roots. However, mechanical disruption of the biofilm should be considered, and copious irrigation and an intracanal medicament must be used to eliminate bacteria and tissue remnants from the root canal system. Data is available on clinical cases of failed revitalization due to infection [9]. Furthermore, animal studies show that the presence of bacteria in the root canal after revitalization does not necessarily cause periapical lesions but results in absence of mineral deposition and thus failed root lengthening and thickening [22].

Generally, the treatment should be performed under isolation with a rubber dam and after disinfection of the working field. It has to be considered that disinfecting agents and medicaments can compromise the viability of surrounding cells, specifically stem cells from the apical papilla [23, 24], and biological considerations have to be included. As for conventional root canal treatment, NaOCl is the irrigant of choice to dissolve pulp tissue remnants and eliminate bacteria. Studies on the effect of NaOCl on stem cells from the apical papilla (SCAP) demonstrated that 0.5 to 3% NaOCl reduced viability to 60%, whereas 6% NaOCl diminished cell numbers below 20% [23]. However, a subsequent rinse with 17% EDTA could reverse these toxic effects, and cell viability could be recovered [23]. EDTA has another positive effect; it enables the release of growth factors on the dentine surface by demineralization [25]. Proteins from the dentine matrix include chemotactic factors, which support cell recruitment, and furthermore growth factors that promote the proliferation and differentiation of stem cells, which might be beneficial for healing and regeneration [26]. Thus, copious irrigation with sodium hypochlorite up to 3% followed by irrigation with 17% EDTA during the first visit, and a rinse with EDTA before the provocation of bleeding during the second visit appear beneficial. The use of auxiliary means to increase the efficacy of irrigation solutions, such as sonic or ultrasonic activation, negative pressure, or the use of side-vent needles to minimise the risk of irrigant extrusion have been looked upon favourably [27].