Abstract
Tooth tissue engineering aims to restore dental structure and function by recapitulating developmental processes using the triad of stem cells, bioactive cues, and scaffolds. Over the past decade, regenerative dentistry has advanced from proof-of-concept studies to early clinical translation, particularly for dentin–pulp and periodontal regeneration. Dental tissue-derived mesenchymal stromal/stem cells, including dental pulp stem cells (DPSCs), stem cells from the apical papilla, and periodontal ligament stem/progenitor cells, are attractive due to accessibility, immunomodulatory properties, and odontogenic potential. Contemporary strategies include cell-free “cell homing” approaches that recruit endogenous stem cells via instructive biomaterials and controlled release of growth factors and cell-based approaches that deliver ex vivo -expanded autologous or allogeneic cells. In regenerative endodontics, clinical protocols such as pulp revascularization have been enhanced by adjunct scaffolds (e.g., collagen and platelet-rich fibrin) and biologic conditioning of dentin to release matrix-bound signaling molecules, while pilot clinical studies demonstrate the feasibility of DPSC transplantation for pulp regeneration. For periodontal defects, multiphasic scaffolds and emerging stem cell injections show promise in improving soft- and hard-tissue outcomes. Technological advances, computer-aided design, three-dimensional (3D) bioprinting, spheroids, and tooth organoids, enable improved spatial control of cell–matrix interactions and may help address the complexity of whole-tooth regeneration. Despite rapid progress, key translational challenges remain, including vascularization/innervation, immune compatibility, infection control, reproducibility, and long-term functional stability. Future efforts integrating organoid biology, smart biomaterials, and standardized clinical-grade manufacturing are expected to accelerate safe and predictable clinical applications of tooth regeneration.