**Tooth Formation: Are the Hardest Tissues of Human Body Hard to Regenerate?**

#### **Juliana Baranova 1, Dominik Büchner 2, Werner Götz 3, Margit Schulze 2 and Edda Tobiasch 2,\***


Received: 29 April 2020; Accepted: 3 June 2020; Published: 4 June 2020

**Abstract:** With increasing life expectancy, demands for dental tissue and whole-tooth regeneration are becoming more significant. Despite grea<sup>t</sup> progress in medicine, including regenerative therapies, the complex structure of dental tissues introduces several challenges to the field of regenerative dentistry. Interdisciplinary e fforts from cellular biologists, material scientists, and clinical odontologists are being made to establish strategies and find the solutions for dental tissue regeneration and/or whole-tooth regeneration. In recent years, many significant discoveries were done regarding signaling pathways and factors shaping calcified tissue genesis, including those of tooth. Novel biocompatible sca ffolds and polymer-based drug release systems are under development and may soon result in clinically applicable biomaterials with the potential to modulate signaling cascades involved in dental tissue genesis and regeneration. Approaches for whole-tooth regeneration utilizing adult stem cells, induced pluripotent stem cells, or tooth germ cells transplantation are emerging as promising alternatives to overcome existing in vitro tissue generation hurdles. In this interdisciplinary review, most recent advances in cellular signaling guiding dental tissue genesis, novel functionalized sca ffolds and drug release material, various odontogenic cell sources, and methods for tooth regeneration are discussed thus providing a multi-faceted, up-to-date, and illustrative overview on the tooth regeneration matter, alongside hints for future directions in the challenging field of regenerative dentistry.

**Keywords:** dentogenesis; amelogenesis; dentinogenesis; cementogenesis; drug release materials; sca ffolds; odontogenic cells; stem cells; whole-tooth regeneration
