# Tooth regeneration in animals. A systematic review

## TL;DR

This systematic review explores current knowledge on tooth regeneration in animals, focusing on bioengineering methods and molecular signaling pathways.

## Contribution

The review systematically evaluates recent studies on dental regeneration in animals, highlighting key genes and signaling pathways involved.

## Key findings

- Four studies showed complete dental regeneration in animal models using genes like Wnt10a, Bmp6, and Grem2a.
- Signaling pathways such as BMP and Wnt, along with factors like FGF and Sox-2, are crucial for tooth development.
- Despite progress, challenges remain in identifying suitable cellular sources and fully understanding regeneration mechanisms.

## Abstract

Methods for creating bioengineered replacement teeth benefit from a detailed understanding of the molecular signaling networks that regulate the development of natural teeth. In oral and craniofacial research, spheroid cultures have been explored, various studies on organoids, such as those of salivary glands, taste buds, and teeth, are being conducted. The aim of this review is to provide a comprehensive overview of the current knowledge on dental regeneration.

This review was registered in PROSPERO (CRD 646053) ad performed following PRISMA guidelines. An electronic search was conducted following the PICO question “In animals (P) subjected to bioengineering techniques (I), is successful dental regeneration achieved (O)?” For evaluating risk of bias, the Arrive scale and the JBI adapted for Quasi-experimental studies tools were used.

A total of 83 articles on dental regeneration from the past 5 years were reviewed, and 4 articles that met the selection criteria were included. The studies describe complete dental regeneration in animal models by stimulating genes such as Wnt10a, Bmp6, Grem2a and the identification of genes and antibodies influencing BMP and Wnt signaling pathways (Sox-2), as well as the expression of key factors such as FGF.

The development of signaling pathways in dental formation has advanced, yet many uncertainties persist, particularly in the regeneration of complete teeth. Despite progress with animal models and genetic editing, identifying suiTable cellular sources and understanding the key genes involved remain essential for future clinical applications.

Key words:Dentogenesis, amelogenesis, dentinogenesis, cementogenesis, drug release materials, scaffolds, odontogenic cells, stem cells, whole-tooth regeneration.