Dental pulp regeneration and bioengineered teeth in clinical practices: A comprehensive review

Pulpal necrosis resulting from carious destruction, traumatic injury, or polymicrobial endodontic infection affects millions of patients globally. Conventional endodontic therapy, while effective, affects the tooth biologically by disturbing the neurovascular pulp complex. The emergence of regenerative endodontics and whole-tooth bioengineering acts as an alternative towards biological restoration of the pulp-dentin complex. Existing clinical trials on pulp regeneration are largely based on small sample sizes, short follow-up durations, and absence of standardized histological outcome criteria. The biological difference between true pulp regeneration and non-specific revascularization remains inadequately studied in majority of protocols. Growth factor delivery systems reported in the literature lack long-term pharmacokinetic data within the root canal microenvironment, and scaffold biomaterial studies are predominantly restricted to in vitro or short-term settings without longitudinal functional assessment. A comprehensive narrative review of peer-reviewed literature was conducted using PubMed, Scopus, and Web of Science databases, encompassing publications from 2000 to 2024. Search terms included "dental pulp regeneration," "dental stem cells," "tooth bioengineering," "regenerative endodontics," "scaffold biomaterials," and "clinical trials pulp revascularization." A total of 54 articles were critically studied, including in vitro studies, animal model investigations, and human clinical trials. The review provides a comprehensive, critical study on the current evidence on dental pulp regeneration and whole-tooth bioengineering. It removes the distinctions between pulp revascularization and pulp regeneration, and evaluate the odontogenic, angiogenic, and neurogenic potential of documented stem cell populations including DPSCs, SHED, SCAP, and periodontal ligament stem cells.