Major characteristics of the dental pulp regeneration process under the stimulation of biomaterials, bioactive Compounds, cells, and molecules: a systematic review

Abstract

Introduction: Dental pulp regeneration is a challenging process that requires sophisticated cellular and molecular mechanisms, as well as biomaterials, to support the pulp's diverse functions, including immune defense, sensory perception, vascularization, and reparative dentinogenesis. Dental pulp contains stem cells with characteristics similar to mesenchymal stem cells. Dental pulp-derived stem cells (DPSC) can regenerate a variety of tissues. Objective: This was a systematic review to elucidate the main characteristics of the dental pulp regeneration process under the stimulation of biomaterials, bioactive compounds, cells, and molecules, as well as to present the main clinical outcomes. Methods: The systematic review rules of the PRISMA Platform were followed. The research was carried out from May to June 2025 in Scopus, Embase, PubMed, Science Direct, Scielo, and Google Scholar databases. The quality of the studies was based on the GRADE instrument, and the risk of bias was analyzed according to the Cochrane instrument. Results and Conclusion: A total of 114 articles were found, and 24 articles were evaluated in full, and 22 were included and developed in this systematic review study. Considering the Cochrane tool for risk of bias, the overall assessment resulted in 25 studies with a high risk of bias and 32 studies that did not meet GRADE and AMSTAR-2. According to the GRADE instrument, most studies presented homogeneity in their results, with X2=91.7%>50%. It was concluded that dental pulp stem cells can promote nerve regeneration through mitochondrial transfer, presenting a promising strategy for improving stem cell-based therapies for nerve injuries. Furthermore, hydrogels specifically developed to regulate the JAG1/Notch signaling pathway have demonstrated potential for pulp tissue regeneration. Mineral Trioxide Aggregate (MTA) is an excellent marginal sealer that prevents bacterial migration into the canal. It is a biocompatible cement that induces dentinogenesis, cementogenesis, and osteogenesis. Calcium hydroxide remains a standard material for use in pulp capping due to its bactericidal effect