Introduction

Pulp necrosis can be the result of deep caries, trauma or dental anomalies. As a consequence, bacterial colonization of the root canal triggers apical periodontitis, which may be initially asymptomatic (asymptomatic apical periodontitis) or associated with pain or other clinical signs of infection (symptomatic apical periodontitis). Classically, the goal of endodontic treatment is to cure apical periodontitis and resolve the associated clinical symptoms by thorough disinfection and filling of the root canal system.

In this context, root canal treatment of immature teeth poses a particular challenge for clinicians because these teeth typically have short roots with thin dentine walls and a wide apical foramen (Figure 9.1a,b). Various treatment options are available, such as apexification with repeated intracanal dressings with calcium hydroxide or the placement of an apical barrier with a hydraulic calcium silicate cement (HCSC). Traditional apexification involves multiple visits and alternating intracanal applications of calcium hydroxide to induce the formation of a calcified barrier at the root apex (1). Once this barrier is formed, the canal can be obturated with gutta‐percha and the tooth can be restored. However, several disadvantages come with this treatment that make it no longer the preferred option. Multiple visits are required, therefore the total treatment time is long, and the prolonged contact of root dentine with calcium hydroxide in combination with the lack of a definitive restoration increases the risk of tooth fracture (2, 3). Given these disadvantages, the current recommendation for immature teeth is to place an apical plug with HCSC and seal the rest of the canal with gutta‐percha (Figure 9.1b). This allows the treatment to be completed quickly and with few appointments (4). However, this will still leave short roots with thin root walls, which means an increased risk of fracture (5, 6).

The vision of endodontic regeneration is based on the restoration of the dentine–pulp complex, where a regenerated pulp tissue will take over all the biological functions of the original pulp, leading to the completion of physiological tooth development.

Biological and Mechanical Goals of Pulp Regeneration

From a biological perspective, regeneration is the process by which tissue is replaced or restored both in form and function (7, 8). Irreversible inflammation or necrosis of the pulp causes clinical and/or radiological symptoms and entails the removal of damaged tissues (9). With the loss of the dental pulp, its various biological abilities are gone (Figure 9.2).

One of the most important biological tasks of the dental pulp is root formation and the secretion of dentine during and after tooth development. In addition, the pulp tissue can resist invading microorganisms through mineral deposition and defend itself through specific and non‐specific immune reactions (10, 11). An additional defence mechanism of the dentine–pulp complex is to ensure an outward flow of dentinal fluid through the tubules (12). Consequently, loss of pulp vitality may allow bacteria to migrate more easily through tubular dentine due to the lack of fluid pressure, which is particularly evident in the significant bacterial invasion of dentine in non‐vital teeth (13). Furthermore, the dental pulp is also a sensitive organ that can detect not only thermal, mechanical or chemical stimuli, but also pathogenic irritants. The loss of the pulp inevitably leads to the destruction of neuronal perception, which may play a role in persistent pain conditions and functional changes of the trigeminal nerve (10, 14).

Besides all the biological implications of pulp loss, the long‐term survival of the tooth may be compromised by the lack of mechanical strength due to possibly incomplete root maturation. (3, 15). The consequences are particularly severe for immature teeth in an early stage of root development (Figure 9.3a). Because of their short roots and thin dentine walls, these teeth are predisposed to fracture (3, 6). Pulp regeneration could facilitate the completion of root development, resulting in increased mechanical strength (Figure 9.3b) and, thus, long‐term survival of affected teeth (16, 17). Due to the thin and fragile root walls of teeth with pulp necrosis in stages 1–3, endodontic regeneration can offer decisive advantages as growth progresses (Figure 9.3c). From stage 4, the root has sufficient stability for both regenerative endodontic approaches and an apical barrier with an HCSC to be suitable for treatment.

Historical Development of Regenerative Endodontics

The field of regenerative endodontics has developed rapidly in recent years and has attracted considerable interest. New biology‐based and minimally invasive concepts are increasingly finding their way into everyday clinical practice and are changing the way of thinking in endodontics and conservative dentistry. However, the idea of regenerating tissue inside the root canal system is not new and dates back to the 1960s. In the paper ‘The role of blood clot in endodontic therapy’, researcher Birger Nygaard‐Østby studied provoked bleeding in the apical third of root canals obturated with gutta‐percha in the coronal two‐thirds (18). He observed partial or complete replacement of the blood clot, mainly by fibrous connective tissue. These findings were forgotten, and attempts to regenerate the pulp were abandoned for several decades before Iwaya et al. made an interesting observation in 2001 (19). In a case report, the authors described the treatment of a lower premolar with incomplete root formation, chronic apical periodontitis and a sinus tract. After disinfection and intracanal medication, the authors still demonstrated vital tissue inside the root canal and applied calcium hydroxide only to the area of the canal entrance. Thirty months after treatment, the completion of root formation was radiographically evident and the tooth responded again to electrical pulp testing (19). A landmark clinical report was finally published in 2004 by Banchs and Trope, translating this observation into a potential treatment approach (20). Similar to the case of Iwaya et al., the tooth involved was a lower premolar with an apical radiolucency and a sinus tract. The root canal was disinfected and treated with an intracanal medication. After the signs of inflammation had subsided, bleeding into the canal was induced by mechanical irritation of the vital apical tissue (Figure 9.4). The resulting blood clot was covered with mineral trioxide aggregate (MTA) at the level of the enamel‐cementum junction. After 24 months, the osseous lesion had healed, root lengthening and thickening as well as apical closure were clearly visible radiographically (20).

This publication was followed by numerous case reports, case series and clinical studies on this biologically based treatment approach known today as revitalization (21, 22). Increasing scientific evidence and experience with revitalization led to official recommendations from the major endodontic societies, the European Society of Endodontology (ESE) and the American Association of Endodontists (AAE), on indications, case selection, procedural details, irrigation, materials and recall (23, 24).

Revitalization

Revitalization has become a well‐established treatment alternative to the apical plug after pulpectomy or pulp necrosis in immature teeth and is now an integral part of the endodontic treatment spectrum. The aim is to create new tissue inside the root canal so that, if successful, the tooth root can continue to grow and increase in length and thickness (24). Generally, the revitalization procedure is based on the induction of bleeding into the root canal, whereby mesenchymal stem cells from the periapical tissue are flushed in (Figure 9.5). A stable blood clot is formed, which acts as a biological matrix and contains blood‐derived growth factors and multipotent stem cells (25). A key to successful revitalization is optimal infection control and sufficient restoration of the tooth. This allows for the development of a structured connective tissue inside the root canal, which is innervated, supplied by blood vessels and has the ability to form new hard tissue (25).

Clinical Protocol

Revitalization usually takes place in two sessions. During the first session, a local anaesthetic is administered, and the tooth is isolated with a dental dam. The necrotic tissue is removed from the root canal, avoiding mechanical debridement of the canal walls. The length of the immature root is determined visually or radiographically, and the canal is disinfected with sodium hypochlorite (NaOCl) just before the apical foramen. A concentration of 1.5–3% is recommended for disinfection and removal of the residual tissue while sparing the local cells (23, 24). The canal is then rinsed with 0.9% normal saline and 17% EDTA to neutralize the cytotoxic NaOCl (27). Subsequently, excel liquid is removed with paper points and the canal is filled with a calcium hydroxide preparation or triple antibiotic paste (TAP: metronidazole, ciprofloxacin and minocycline) and adhesively sealed until the second appointment (23, 24).

After 2–4 weeks, the clinical situation is assessed and, if the tooth is asymptomatic, revitalization may be performed (Figure 9.6). After local anaesthesia, the tooth is isolated again with dental dam and intracanal medication is removed by rinsing with 17% EDTA. This agent has several effects, and it exposes collagen fibres as well as bioactive proteins on the dentine surface (28). After another rinse with saline, the root canal is dried and bleeding is induced by irritation of periapical tissues with an endodontic file, e.g. a pre‐bent ISO 30 Hedström file (Figure 9.7a). The blood should reach approximately 2 mm below the cemento‐enamel junction and be left to coagulate (Figure 9.6). The coagulum is then covered with a collagen matrix for stabilization, followed by application of an HCSC in direct contact (Figure 9.7b). At this point, a radiographic control is indicated and the tooth is sealed with an adhesive restoration (23, 24).