Elsevier

Current Opinion in Cell Biology

Volume 61, December 2019, Pages 126-131
Current Opinion in Cell Biology

Regrowing a tooth: in vitro and in vivo approaches

https://doi.org/10.1016/j.ceb.2019.08.002Get rights and content

Highlights

  • In situ revitalization of the lost replacement capability during tooth evolution will become possible.

  • In vivo biological repair of the damaged tooth has shown clinical application.

  • In vitro successful generation of an implantable tooth germ would make whole tooth regeneration become a reality in dental practice.

Biologically oriented regenerative dentistry in an attempt to regrow a functional tooth by harnessing the natural healing capabilities of dental tissues has become a recent trend challenging the current dental practice on repairing the damaged or missing tooth. In this review, we outline the conceptual development on the in situ revitalization of the tooth replacement capability lost during evolution, the updated progress in stem-cell-based in vivo repair of the damaged tooth, and the recent endeavors for in vitro generation of an implantable bioengineered tooth germ. Thereafter, we summarize the major challenges that need to be overcome in order to provide the rationale and directions for the success of fully functional tooth regeneration in the near future.

Introduction

According to The National Health and Nutrition Examination Survey on oral health and dental care in the United States between 1999 and 2004, adults aged from 20 to 64 have an average of 3.28 decayed or missing permanent teeth. The loss or damage of natural teeth affects numbers of aspects of human’s daily life, and is widespread, especially in older people, becoming a global health problem in the aging societies [1]. While conservative approaches in dental practice using inorganic materials [2] that would fail with time and could not provide the full function of teeth, regrowing or repairing one’s own teeth is an ultimate alternative [2]. Recently, with the advanced understanding of tooth evolution and the underlying mechanisms regulating the morphogenesis of natural tooth in vivo, stem cell-based bioengineering is making it possible for in vivo and in vitro regeneration of a functional tooth. This review provides an overview of various paradigms of tooth tissue regeneration and outlines the challenges facing the field.

Section snippets

Tooth regeneration in situ by revitalizing the tooth replacement capability lost during evolution

Teeth and dermal denticles were previously recognized as derivatives of a homologous developmental unit, odontode [3]. Recent studies found that vertebrate teeth may emerge phylogenetically from the expansion of the odontogenic competence from the external dermal denticles [4]. When probably the first teeth emerged in Condonts as a series of odontodes throughout the oro-pharyngeal cavity in lower vertebrate [3], they had the regenerative capacity in adults. Almost all the vertebrates, including

Regenerating a functional tooth based on extensive knowledge of tooth development

The similarity of tooth development in humans and mice has made the mouse a widely used model for studying tooth development [9]. In mice, tooth development is initiated by the local thickening of the dental lamina, referred as the dental placode that becomes visible at embryonic day (E)11.5. Classical tissue recombination studies have shown that the epithelium at E11.5 possesses the odontogenic potential, the capability that can induce tooth formation when recombined with non-dental

Rebuilding tooth structures by biologically oriented repair in vivo

The tooth is an intricate organ composed of the highly mineralized tissues (enamel, cementum, and dentin) and their enclosed soft tissues [18]. During tooth development, the ameloblasts, which produce enamel, die before tooth eruption. Thus, it is impossible to biologically repair/regenerate the worn out enamel [23]. Traditionally, acellular materials are used for the remineralization of enamel. However, it is difficult to recreate the hierarchical structure similar to natural enamel on the

Recapitulating the developmental program for whole tooth bioengineering in vitro

While the feasibility for functional tooth replacement by tooth germ implantation has been proved in animal models [39••,40,41], the identification of easily accessible and appropriate sources of human adult stem cells for bioengineering an implantable tooth germ for future clinical application poses a challenge. Taking advantage of mouse embryonic dental epithelium or mesenchyme that possesses the odontogenic potential, various sources of adult stem cells have been tested for their odontogenic

Challenges and outlook

Biological, cell-based repair/regeneration of a functional tooth (bio-tooth) in the desired location should be the ideal dental treatment approach. Recently, although stem cell-based transplantation has made tremendous progresses in the biologically oriented repair of damaged teeth in situ, the ultimate goal of regenerating a functional whole tooth has not been achieved yet. To construct a tooth with full function, one prevalent biological approach is to recapitulate the tooth ‘developmental

Conflict of interest statement

Nothing declared.

References and recommended reading

Papers of particular interest, published within the period of review, have been highlighted as:

  • • of special interest

  • •• of outstanding interest

Acknowledgement

The cited work conducted in the Chen Lab has been supported by the National Institute of Dental & Craniofacial Research of N.I.H. under award numbers (R01DE012329, R01DE015123, R01DE024152).

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