Apexification is defined as a ‘method to induce calcified barrier in a root with an open apex or the continued apical development of an incomplete root in teeth with necrotic pulps’ [5].

Traditionally the clinical protocol for ‘apexification’ involved the placement of calcium hydroxide as an intra-canal medicament to eliminate intra-radicular infection and induce an apical barrier requiring multiple visits and a protracted treatment, which could take several months [3, 6]. Recently, an alternative one-visit apexification protocol involving the use of mineral trioxide aggregate has gained popularity as a means of creating an artificial barrier at the open apex to which a hard tissue barrier can readily form with similar outcomes to using calcium hydroxide. In the apical barrier technique, a biocompatible barrier material is placed at the apex to facilitate obturation. Mineral trioxide aggregate is the material of choice due to its optimal sealing ability, biocompatibility and ability to induce hard tissue and set in a moist environment. The advantage of using this technique is that the treatment time is reduced to one or two appointments with significant expedition of treatment with similar outcomes and prognosis [7–12]. The disadvantage of using either calcium hydroxide or mineral trioxide aggregate has been the inconsistency of achieving continued root maturation. Teeth treated with either techniques are at greater risk to root fracture as a consequence of thin dentinal walls resulting in the premature loss of the tooth [13–16].

Revascularization of avulsed and replanted immature teeth with open apices is well established and achievable provided optimal replantation techniques are used. Prompt replantation with minimal extra-oral dry periods and ideal root development stage (open apices of greater than 1.1 mm) are the prerequisites for revascularization [17]. Regeneration (revitalization) of infected necrotic pulp tissue has been an important issue in endodontics for more than a decade. Regenerative endodontics has been defined as ‘biologically-based procedures designed to physiologically replace damaged tooth structures, including dentine and root structures, as well as cells of the pulp-dentine complex’ [5]. Based on a series of case reports, there appears to be evidence that new soft tissue can enter the root canal with the potential for subsequent hard tissue deposition resulting in continued root maturation [18]. Current approaches for treating the traumatized immature tooth with pulpal necrosis do not reliably achieve the desired clinical outcomes, consisting of healing of apical periodontitis, promotion of continued root development and restoration of the functional competence of pulpal tissue. An optimal approach for treating the immature permanent tooth with a necrotic pulp would be to regenerate functional pulpal tissue [19, 20].

Over the last decade, a number of case reports have been reported in the literature demonstrating this new revitalization approach in achieving tissue generation and regeneration. Continued root development has been demonstrated in cases that presented as infected and necrotic with occasional draining sinuses. As a result, it may be predicted that traditional apexification methods employed may become of historical interest only [21, 22]. These case reports advocate the use of a triple antibiotic paste to eliminate the intra-radicular infection, a prerequisite for setting the conditions to allow for subsequent revascularization [23–29]. The triple antibiotic paste in these cases consists of a combination of ciprofloxacin, metronidazole and minocycline, which has been shown to reliably disinfect the root canal system. The disinfection of the root canal is carried out without any mechanical debridement. Irrigation using sodium hypochlorite is used and then the antibiotic paste placed for a period of time. At the second appointment, a blood clot is produced to the level of the cemento-enamel junction to provide a scaffold for the ingrowth of new tissue. The cervical portion of the tooth is sealed with MTA and a bonded resin composite restoration [30]. The formation of a blood clot is the key to success, and this crucial step, which is essential for the stimulation of revascularization, is unpredictable. Currently research strategies are underway in order to understand fully the true nature of this ‘regenerated tissue’ and provide future potential synthetic matrices, which will act as more predictable scaffolds [31].

Although regenerative endodontic treatment causes root development, there are several drawbacks and unfavourable outcomes that can occur [32]. Tooth discolouration has been cited and is related to the use of either minocycline in the triple antibiotic paste or MTA coronally [33, 34]. Ideal root development is not achieved in all cases, suboptimal barrier placement has been an issue, and there has been failure to induce bleeding in some reports [34, 35].

In summary, the question is no longer ‘can regenerative endodontic procedures be successful?’ Instead, the important question facing us is ‘what are the issues that must be addressed to develop a safe, effective, and consistent method for regenerating a functional pulp-dentine complex in our patients?’ [36]. Additional translational studies and clinical trials evaluating the different aspects of this procedure are required in order to understand the many interrelated aspects that could result in better and more predictable outcomes [37]. The idea of replacing severely compromised teeth or missing teeth in the future using stem cells as a precursor may well be on the horizon making dentures and dental implants obsolete [38].