The next generation of regenerative dentistry: From tooth development biology to periodontal tissue, dental pulp, and whole tooth reconstruction in the clinical setting.

In modern dentistry, prosthetic approaches such as implants and dentures have been developed as symptomatic solutions for tooth loss. However, the complete regeneration of teeth and periodontal tissue, an ultimate aspiration of humanity, remains unachieved. Recent advancements in fundamental scientific technologies, including single-cell RNA sequencing and spatial transcriptomics, have significantly advanced our molecular understanding of tooth development, paving the way toward achieving this goal. This review summarizes the fundamental processes of tooth development in humans and mice, recent findings from basic research, and current clinical applications in dental regenerative medicine, including periodontal, alveolar bone, and dental pulp regeneration using cellular approaches. Building on accumulated scientific knowledge, the complete regeneration of teeth and periodontal tissues may be achievable in the near future. We discuss the potential of emerging approaches, such as organoids derived from pluripotent stem cells and xenotransplantation using genetically modified animals, to transform dental medicine. These innovative concepts and integrated technologies hold the promise of enabling the regeneration of fully functional teeth and periodontal tissues.