Regenerative endodontics: towards a new standard for mature and immature teeth?

The treatment of necrotic permanent teeth presents the clinician with a technical dilemma: how to reconcile root canal disinfection with the restoration of tissue vitality? While the management of immature teeth is documented by Wikström et al. (2021) to promote apexogenesis, the application of regenerative endodontic procedures (REP) to mature teeth remains an area under active exploration. The stakes are high: can an inert canal be transformed into a bioactive tissue, even after the closure of the apex?

This review, including the ESE S3 guidelines (Duncan & El-Karim, 2025), aims to evaluate the clinical efficacy of REPs compared to conventional protocols. The randomised clinical trial by Arslan et al. (2019), involving 30 mature teeth with periapical radiolucency, specifically compares the use of platelet-rich fibrin (PRF) to blood clot (BC). The objective is to measure the healing kinetics and the potential for return of sensitivity.

The tested hypothesis, supported by case reports such as that of Nagas et al. (2018), suggests that stem cell recruitment via periapical bleeding or the use of autologous matrices enables intracanal tissue regeneration. Should the practitioner today consider these bio-scaffolds as a predictable alternative to conventional root canal obturation to induce long-lasting periapical healing?

Methodological rigour between systematic reviews and clinical trials

The analysed database combines a systematic review (Wikström et al., 2021) on the long-term treatment of immature teeth and the recent S3-level clinical guidelines of the European Society of Endodontology (ESE, Duncan & El-Karim, 2025). These guidelines are based on a rigorous consensus process and a synthesis of current literature.

The experimental component is based on several randomised clinical trials (RCTs) and case series specifically targeting mature permanent teeth presenting with pulp necrosis and apical periodontitis:

• Trial protocols: Arslan et al. (2019) and Youssef et al. (2022) conducted preliminary randomised clinical studies to evaluate regenerative endodontic procedures (REP) on mature teeth.
• Tissue analysis and imaging: The study by El-Kateb et al. (2020) used magnetic resonance imaging (MRI) for the quantitative evaluation of intracanal regenerated tissues.
• Scaffolds and sensitivity: The use of platelet-rich fibrin (PRF) was evaluated by Nageh et al. (2018) and Mittal et al. (2021), the latter comparing different types of scaffolds for the return of pulpal sensitivity.
• Longitudinal follow-up: The comparative evaluation by Jha et al. (2019) extended over an 18-month follow-up period to validate the stability of the results.

Finally, the management of complex cases, including cystic inflammatory lesions or persistent periodontitis following conventional treatment, has been documented through case series (Saoud et al., 2014, 2015, 2016) and clinical reports (Paryani and Kim, 2013; Nagas et al., 2018).

Results: A credible alternative to conventional treatment

Compiled clinical data show that regenerative endodontic procedures (REP) are no longer exclusive to immature teeth. The randomised study by Arslan et al. (2019), comparing REP to conventional endodontic treatment (RCT) in mature teeth with apical periodontitis, reports no statistically significant difference in terms of clinical and radiographic success.

Beyond simple periapical healing, the recovery of intracanal sensory activity constitutes a major outcome of these regenerative approaches:

• Abou Samra et al. (2018): In a series of 7 cases of mature teeth treated by revascularisation, all demonstrated clinical and radiographic success at 12 months. Notably: 3 out of 7 cases showed a positive response to sensitivity tests.
• Paryani and Kim (2013): Their work on two cases of mature teeth confirms this trend with complete healing of the lesions and a documented return of pulpal sensitivity.
• Nagas et al. (2018): The qualitative observation of the revitalisation of necrotic mature permanent incisors confirms the feasibility of the procedure and the resolution of inflammatory signs.

In terms of imaging, the results show a systematic reduction in periapical radiolucencies in the REP groups. Unlike protocols for immature teeth, the main objective here is not apexogenesis (already completed), but tissue healing and functional reinnervation, achieved in a significant proportion of the reported cases.

A paradigm shift: the revitalisation of mature teeth

The idea that regenerative endodontic procedures (REPs) are exclusive to immature teeth is now outdated. The case series by Saoud et al. (2014, 2015, 2016) and Abou Samra et al. (2018) demonstrate genuine clinical efficacy on mature permanent teeth presenting with pulp necrosis and periapical lesions, even persistent or cystic ones. The study by Youssef et al. (2022) further confirms that REP is a viable alternative to conventional treatment, promoting apical healing without the use of inert obturation materials.

The major contribution of these studies lies in the return of pulpal sensitivity. Nageh et al. (2018), through the use of PRF, and Mittal et al. (2021) report a recovery of sensory vitality, suggesting the formation of vascularised and innervated connective tissue. Quantitatively, the randomised trial by El-Kateb et al. (2020) uses MRI to confirm the presence of regenerated intracanal tissues, providing objective evidence for what was previously only a clinical observation.

However, caution is still advised. Although the ESE S3 guidelines (Duncan & El-Karim, 2025) incorporate these advances, the studies by Nagas et al. (2018) and the trials by Arslan et al. (2019) rely on sample sizes that are still modest. The long-term predictability of REP compared to conventional root canal treatment on mature teeth, in terms of mechanical stability, has yet to be consolidated by larger cohorts.

Towards biological endodontics on mature teeth?

The clinical studies by Saoud et al. (2016) and Arslan et al. (2019) challenge the dogma by demonstrating that regeneration is no longer reserved for open apices. In cohorts of 10 and 20 necrotic mature teeth, apical healing rates reach 100%. Remarkably: Saoud reports a return of cold sensitivity in 80% of cases (8/10), a result unattainable with conventional obturation.

In practical terms, for the practitioner:

• Dare to revitalise: Consider the regenerative procedure for mature teeth if the patient expresses a desire for sensory preservation, with an 8 out of 10 chance of regaining positive pulpal sensitivity.
• Manage expectations: Inform the patient that while REP enables biological restoration, its radiographic success rate (100%) is equivalent, but not superior, to conventional endodontic treatment.
• Rigorous disinfection: As success relies on the triad (stem cells, scaffold, growth factors), chemical disinfection remains the critical pillar, especially in these narrow canals where the induced blood flow is more limited.

Technical glossary of regenerative endodontic therapies

Mature permanent teeth: Teeth that have completed their root development with complete apical closure. Historically excluded from regeneration protocols, they represent the new clinical challenge of recent studies that seek to transpose the successes achieved in open apices to narrow canal systems.

Apical periodontitis: Inflammation of the periradicular tissues resulting from an endodontic infection. In the cited sources, it is often associated with extensive lesions, described as "cyst-like" (pseudocystic), whose radiological healing is a major criterion for therapeutic success.

Pulp necrosis: A pathological condition characterised by the death of the pulp tissue, eliminating all intra-canal immune defence capacity. It is the primary indication for regenerative procedures which aim to replace this inert tissue with vital tissue capable of restoring the biological function of the tooth.

Regenerative endodontic procedures (REP): Therapeutic protocols based on the principles of tissue engineering. They rely on the interaction between stem cells (often derived from the apical papilla), signalling molecules and a biological scaffold to restore the dentine-pulp complex.

Periapical radiolucency: Radiological manifestation of inflammatory bone resorption at the apex. Its quantitative monitoring is essential to evaluate treatment efficacy, with the reduction of this area indicating effective bone healing following disinfection and revascularisation.

Revascularisation: Clinical technique inducing intentional periapical bleeding to deliver mesenchymal stem cells and growth factors into the canal lumen. It acts as the biological driver enabling the formation of new living tissue in an initially necrotic tooth.

Revitalisation: A term often used interchangeably with revascularisation, emphasising the aim of restoring tissue vitality and, ideally, pulpal sensitivity to a treated tooth, as opposed to conventional inert obturation.

Information intended for healthcare professionals. This content may contain errors or truncated summaries. We recommend always checking with the original source article. Delynov disclaims all liability regarding the use of this information. This document is not intended for patients or the general public.