Dear Colleagues,

Over the last two decades, the development of a biologically based treatment for immature necrotic teeth has opened an exciting new field of research in endodontics. Regenerative endodontic or revitalization is aimed at regenerating the form and function of pulp tissue and inducing further root development of the immature tooth to improve its prognosis. In vivo studies have shown satisfactory clinical outcomes with resolution of signs and symptoms, healing of periapical lesions, and root development in most cases, together with a positive response to vitality pulp testing in some cases. However, it is also known that the newly formed tissue after therapy is neither pulp nor dentine but an ectopic tissue similar to cementum or osteodentin, and an unorganized connective tissue that lacks cells with a distinct odontoblast phenotype.

The material used during the therapy, the cause of pulp necrosis, and the remaining infection in the root canal system and periapical tissues seem to play key roles in the lack of formation of tissues that resemble the original pulp and dentine, as well as in the clinical success of the therapy. However, since the early case reports published at the beginning of the 21^st Century until now, much has been learned regarding the factors influencing the biological mechanisms and outcomes of the therapy.

Regenerative endodontics is now facing now the challenge of identifying all possible factors that hinder odontoblast-like differentiation and secretion of tubular dentin in vivo in order to plan the most effective therapeutic strategies. Likewise, it is necessary to identify unique molecular markers for the odontoblast phenotype to evaluate the type of tissue formed after the therapy with scientific certainty, and finally, to evaluate the feasibility of applying this treatment in mature necrotic teeth, which would benefit from the revascularization and recovery of the natural immune system of the pulp.

This Special Issue of Cells aims to provide a comprehensive global view of the current state of knowledge on the regeneration/repair of the pulp–dentin complex. Potential topics include, but are not limited to (i) cellular and molecular mechanisms related to the regeneration and repair of the pulp–dentin complex; (ii) the clinical outcomes of regenerative endodontics in immature necrotic teeth; (iii) the most recent advances in regenerative endodontic therapy for immature necrotic teeth; (iv) the application and outcomes of regenerative endodontics for mature necrotic teeth, having a special focus on aspects that might make the application of the therapy a greater clinical challenge in closed apex teeth; and (v) the challenges and future perspectives of regeneration of the dentin–pulp complex in teeth with necrotic pulp.

Researchers and university groups are invited to share relevant experimental, clinical, and review studies from both basic and translational sciences.

Prof. Massimo Del Fabbro
Dr. Cristina Bucchi
Guest Editors

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• regenerative endodontics
• revitalization
• pulp regeneration
• necrotic teeth
• tubular dentine
• odontoblasts
• pulp cells