Description of the condition

Dental caries and traumatic injuries are common problems in young children with immature permanent teeth, often leading to pulp necrosis, which is defined as a clinical diagnostic category indicating the death of the dental pulp (Glossary of endodontic terms 2015). Dental pulp is a richly vascularized and innervated specialized connective tissue of ecto‐mesenchymal origin; contained in the central space of a tooth, surrounded by the dentine, with inductive, formative, nutritive, sensory and protective functions (Glossary of endodontic terms 2015).

An immature permanent tooth is a young/newly erupted permanent tooth with incomplete root apex formation. After a permanent tooth emerges in the mouth, it usually takes three more years for the root development to complete (Fouad 2009). The shape and form of these developing roots are determined by a two‐layered cellular structure called the Hertwig's epithelial root sheath (HERS) (Bhasker 1991). Development of roots in the postemergent years consists of the increase in root length, increase in root wall thickness and narrowing of root canals in the apical region (root apex). Any disruption in the blood supply to HERS as a result of pulp necrosis can disrupt cell proliferation and differentiation causing cessation of root development. Abnormal hard tissue deposition may also occur in this situation (Torneck 1982). Immature roots with necrotic pulps in young permanent teeth are therefore characterized by wide root canals with open apex and thin walls.

Dental caries or traumatic injuries may cause microbes to enter the dental pulp. This may cause inflammatory changes in the pulp (pulpitis) that are irreversible in nature (Andreasen 1990). Pulp necrosis (death) is the ultimate outcome of irreversible pulpitis, which is a clinical diagnosis based on subjective and objective findings indicating that the clinically normal inflamed pulp is incapable of healing (Glossary of endodontic terms 2015). The susceptibility of microbial invasion of dental pulp due to trauma or dental caries increases after emergence of the young permanent tooth in the oral cavity, when the roots are still developing.

The global burden of the condition in children and adolescents is significant. Pulp necrosis as a consequence of untreated dental caries in young permanent teeth is very common in low‐income and middle‐income countries (Monse 2010). Traumatic dental injuries play a significant role in causing the pulp necrosis and subsequent infection of the root canal system in immature permanent teeth. A prevalence in the range of 17% to 100% has been reported for pulp necrosis as a consequence of different types of traumatic dental injuries (Jacobsen 1977; Lee 2003; Robertson 1996) depending on the severity. In a review which included last 12 years of published articles, it was reported that the majority of dental injuries occurred before 19 years of age affecting 25% of all school children (Glendor 2008).

Description of the intervention

Immature permanent teeth with necrotic pulps are difficult candidates for conventional root canal fillings. They also have an increased susceptibility to root fractures after treatment (Trope 2010).

In the past many different treatments have been proposed for immature permanent teeth with necrotic pulps. These include custom fitting of filling materials like gutta percha (Stewart 1963), paste fills into wide canals (Friend 1967), and periapical surgeries (Ingle 1965). The associated limitations of these procedures diverted interest towards therapies that aimed to induce a calcified barrier in a root with open apex or promote continued root development of an incompletely formed root in teeth with necrotic pulps. These interventions are termed as apexification procedures (Glossary of endodontic terms 2015) and were popularised by Frank 1966. Calcium hydroxide was the favoured choice for these procedures. The underlying principle was removal of the necrotic pulp, followed by thorough debridement of the canal and control of infection.

The practical problems of multiple visits, nature of hard tissue formed and duration of treatment are limitations of the apexification procedure. The 'apical barrier technique' was proposed to solve these disadvantages. This technique involved placement of a matrix in the apical region to prevent extrusion of endodontic filling materials (Glossary of endodontic terms 2015). A number of materials can be used to form an apical barrier, MTA (mineral trioxide aggregate) remaining a popular choice (Shabahang 1999). Several interventions to reinforce the root walls have also been proposed (Pitt Ford 1979).

'Regenerative endodontic procedures (REPs)' denote the most recent proposal to manage immature permanent teeth with necrotic pulps. In these situations, pulp may be replaced either by creating new internal tissues or delivery of appropriate external tissues.

The first kind of REP evolved from laboratory experiments that described a role for blood clots in endodontic therapy (Ostby 1961). The growth of new blood vessels (revascularization) in necrotic root canal systems occurred after disinfection followed by provoked bleeding by over instrumentation into the periapical tissues. The induced blood clot acts as a matrix of undifferentiated mesenchymal cells, which leads to new pulp‐like tissue formation (Murray 2007). This tissue in turn may produce deposition of calcific material at the apex and on the lateral dentinal walls (Banchs 2004; Iwaya 2001). REP treatments have evolved as alternatives to conventional one‐step or multi‐visit apexification and have been investigated in animal experiments (Cvek 1990; Yanpiset 2000), case reports in humans (Iwaya 2001) and original research (Ding 2009; Shah 2008). The 'blood clot' based revascularization has the advantage of being simple and free from immune reactions. The major challenge however is the maintenance of a sterile environment so that new tissue can regenerate. The potential presence of residual biofilms in root canals of immature permanent teeth with necrotic pulps adds uncertainty, variability and unpredictability to the outcomes of the procedure (Nair 2014).

Other techniques focus on the delivery of cells, matrices/scaffolds, and possibly genes to the necrotic pulp canals to support regeneration of newer tissue. These procedures are currently, still at the laboratory stage or only described in animal models. The challenge of a sterile environment remains, with uncertainty as to methods of delivery, choice of cell sources, ethical issues, and controlling any adverse effects.

The interventions for immature permanent teeth with necrotic pulps can, therefore, be broadly categorized as.

• Multi‐step apexification techniques.

• Single‐step apexification techniques.

• Apical plug techniques.

• Root strengthening interventions.

• Regenerative endodontic procedures/interventions.

How the intervention might work

Most of the interventions to manage young permanent teeth with necrotic pulps intend to create a natural or an artificial apical barrier at the wide open apices, with or without continued root apex development. The basic principles underlying all interventions involve removal of necrotic pulp, debridement of the canal and control of infection with or without an antiseptic medicament. It is suggested that complete removal of necrotic pulp is a prerequisite for apical closure as it may, otherwise, if left in the canal, initiate strong inflammatory reactions in the periapical region. This leads to the use of many antibiotics and antiseptic pastes combined with repeated debridement of canals for multi‐visit apexification procedures. Medicaments such as calcium hydroxide, with its high pH, cause superficial contact necrosis with the periapical tissue, arousing a low‐grade irritation of the underlying tissue sufficient to produce a matrix that mineralises (Schröder 1971). In addition, the antimicrobial activity of calcium hydroxide creates conditions conducive to the apical barrier formation (Jevelet 1985).

Total treatment time may vary in multi‐visit apexification, depending on the medicament used, presence of periapical pathology initially (Cvek 1972), frequency of medicament replacement (Finucane 1999), and age of the patient (Mackie 1988).

The single‐visit apexification techniques differ from the multi‐visit techniques only in that they help in establishing an apical stop enabling the root canal to be filled immediately. Attempt is not made for inducing natural apical stop; rather an artificial stop is created (Harbert 1996; Schumacher 1993). Artificial apical stops also known as 'apical plugs', are most commonly formed with the help of cements such as MTA. Apical plugs help to create an artificial barrier to prevent extrusion of filling material (pushing out of material through the apex into the surrounding soft tissue and bone) and also through its own strength, to reinforce the weak apical region dentine walls.

Regenerative endodontic interventions are based on the rationale that under suitable circumstances, notably free from infection, the cells in the apical papilla (HERS and SCAP‐ stem cells from apical papilla) will complete root maturation. Case reports (Pindborg 1955) in human teeth and some in vitro studies (Sonoyama 2008) have provided evidence for HERS and SCAP respectively as important sources of undifferentiated cells forming hard tissue.

Root strengthening interventions differ in their working mechanism from others with respect to strengthening the cervical area of the roots in particular. The cervical area of the immature root is the most crucial area susceptible to fracture under the forces of mastication or due to any secondary injury (Rabie 1986). Therefore, materials with reinforcing effect must be chosen with qualities like ease of manipulation, preventing microleakage, ease of removal if needed, and consistent adherence to the dentine walls (Stuart 2006). The procedures that strengthen root structures against fracture in immature young permanent teeth with necrotic pulps use resin‐based root canal sealers (Trope 1992), glass ionomer based root canal sealers (Pitt Ford 1979), or fiber reinforced post placement in the canals (Ferrari 2002).

Why it is important to do this review

At present there is no evidence‐based guidance to manage immature permanent teeth with necrotic pulps (American Association of Endodontists 2016). Even though the evidence base is lacking for this condition there are practice guidelines to advise clinicians (AAPD Reference Manual 2014).

There is clinical uncertainty as to which regenerative endodontic procedure should be used to manage immature permanent teeth with necrotic pulps. A recent recommendation (Garcia‐Godoy 2012) to carry out regenerative techniques conflicts with previous guidelines (Chen 2012; Chueh 2006; Huang 2008a; Huang 2008b; Lenzi 2012; Neha 2011; Thibodeau 2007) which propose that regenerative procedures first be considered when conventional non‐surgical orthograde endodontic treatment, root canal treatment, root canal obturation, apexogenesis, apexification, or pulpotomy have been attempted and failed.

Thus it is important to undertake this Cochrane Review to try to resolve this uncertainty.