Biologically Driven Tooth Regeneration: A Scoping Review of Stem Cell-Based Approaches

Regenerative dentistry is an emerging branch of medicine that focuses on restoring biological tooth structures using stem cells, biomimetic scaffolds, and signaling factors, rather than relying on traditional man-made materials. Current treatments, such as fillings and crowns, can rebuild lost tooth structures but cannot replicate the structure and function of dentin-pulp tissues. Recent preclinical and early human studies have explored various stem-cell sources, including dental pulp stem cells (DPSCs), stem cells from exfoliated deciduous teeth (SHED), and periodontal ligament stem cells (PDLSCs). Among these, DPSCs and SHED have been the most extensively investigated. Most studies have shown that, when combined with pro-angiogenic factors such as vascular endothelial growth factors (VEGFs) and fibroblast growth factors (FGFs), collagen and hydrogel scaffolds are effective in regenerative dentistry. These studies have demonstrated successful tissue formation, mineralization, and vascularization in animal models and early human trials. However, considerable variability exists among studies due to differences in experimental design, stem-cell sources, scaffold materials, and growth-factor use, leading to inconsistent outcomes. Despite these advances, the literature remains fragmented and largely preclinical. Only a limited number of human studies are available, and variability among studies remains substantial. Existing reviews often focus on a single component, such as a specific stem-cell type or scaffold property, rather than integrated regenerative systems. This scoping review, conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines, synthesizes available preclinical and early clinical evidence and identifies combinations of stem cells, scaffolds, and signaling molecules with the greatest potential for predictable dental tissue regeneration.