Dental pulp stem cells (DPSCs) are multipotent mesenchymal stem cells with demonstrated potential for regenerating dental and periodontal tissues. This systematic review aimed to critically evaluate the regenerative potential, biological properties, and translational prospects of DPSCs in dental and periodontal tissue engineering, based on in vitro, in vivo, and clinical interventional studies published between 2010 and 2025. A comprehensive literature search was conducted in PubMed, Web of Science, Embase, and Scopus using combinations of keywords related to DPSCs, dental/periodontal regeneration, and tissue engineering. Quality assessment was performed using the Downs and Black checklist, and the risk of bias was also evaluated with RoB 2 and ROBINS-I tools. A total of 12 interventional studies (9 experimental and 3 clinical trials) were included. DPSCs consistently indicated high proliferation, multilineage differentiation, immunomodulatory capacity, and resistance to inflammatory and senescence-inducing conditions compared to other mesenchymal stem cell sources. Preclinical studies demonstrated the enhanced regeneration of dental pulp, dentin, periodontal ligament, cementum, and alveolar bone using DPSCs, with or without scaffolds and bioactive cues. Clinical trials reported the safety of autologous DPSCs and improvements in pulp vitality, probing depth, clinical attachment level, and bone defect filling; however, sample sizes were limited, and evidence for superiority over standard therapies remains preliminary. DPSCs possess significant regenerative potential for dental and periodontal tissue engineering, supported by robust preclinical evidence and early clinical studies. Nevertheless, clinical translation is constrained by limited trial data, methodological heterogeneity, and regulatory challenges. Future research should focus on standardized protocols, long-term clinical outcomes, and integration with advanced tissue engineering strategies such as biomimetic scaffolds, organoids, and gene-editing approaches to fully realize the therapeutic potential of DPSCs. • DPSCs were demonstrated to have superior proliferative and regenerative properties compared to other MSC sources. • The enhanced resistance of DPSCs to senescence and inflammatory stimuli was observed. • DPSCs were shown to efficiently differentiate into odontogenic and osteogenic lineages in vitro. • The successful regeneration of pulp-like tissue, dentin, cementum, and periodontal tissue by DPSCs was reported in animal models. • The safety and potential efficacy of autologous DPSCs were confirmed in clinical pilot studies. • Adjunct strategies, such as platelet-rich fibrin, 3D scaffold-free constructs, and herbal extracts, were found to augment DPSCs regenerative capacity. • The promising role of DPSCs in dental and periodontal tissue engineering was concluded, indicating their potential for clinical application.
Asghari et al. (Mon,) studied this question.