Dental Pulp Regeneration: A Comprehensive Review of Stem Cells, Biomaterials, and Bioactive Cues

Dental pulp regeneration (DPR) is an important research direction in regenerative endodontics that seeks to restore pulp vitality, sensation, immune defense, and the pulp-dentin architecture rather than merely retain a non-vital tooth. This review provides a mechanistically coupled and clinically focused synthesis of three interacting elements: stem/progenitor cells, biomaterials, and bioactive signals. Dental and non-dental cell sources are compared with emphasis on their angiogenic, neurogenic, odontogenic, and immunomodulatory characteristics and on the donor- and culture-dependent variability that affects product potency. Rather than presenting scaffolds only by material class, the review offers a structured critical correlation of stiffness, viscoelasticity, porosity, degradation, and bioactivity with cell fate, extracellular matrix organization, vascularization, and the risk of ectopic mineralization. Regulated growth-factor presentation, peptide-based signals, gene-activated constructs, extracellular vesicles, immune-instructive materials, and mechanobiological approaches are evaluated according to the highest experimental model in which they have been demonstrated. A stratified research framework is proposed to examine how age, inflammatory phenotype, systemic disease, apical anatomy, and regional heterogeneity of the pulp microenvironment may influence regenerative responses. The supporting evidence remains predominantly in vitro or preclinical. Cell-free regenerative endodontic procedures are clinically accepted for selected immature necrotic teeth with open apices, but available human histology most often demonstrates repair rather than recreation of a native pulp-dentin complex. Human cell transplantation studies remain small and early-phase, and advanced gene-, vesicle-, biofabrication-, and computational strategies have not yet demonstrated clinical efficacy. The framework is therefore presented as an evidence-graded research roadmap rather than a description of established personalized therapy.