Regrowing a tooth: in vitro and in vivo approaches
Graphical abstract
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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Parallels in signaling between development and regeneration in ectodermal organs
2022, Current Topics in Developmental BiologyCitation Excerpt :Ex vivo organ germ culture experiments, which involve culturing mesenchymal cells with epithelial cells layered on top using a gel matrix, have shown that the epithelial and mesenchymal cells from embryonic tooth germs can be used to grow functional teeth (Oshima, Ogawa, & Tsuji, 2017) in serum-supplemented media. The tooth mesenchymal stem cell populations can regenerate dental pulp and periodontal tissues (Huang et al., 2021; Li, Tang, Wang, & Chen, 2019; Volponi, Zaugg, Neves, Liu, & Sharpe, 2018). Fgf, Tnfα, Bmp, Wnt, along with various additional growth factors, are involved in the various aspects of dentin regeneration, odontogenic mesenchymal stem cell migration and differentiation.
Multipotent stem cells from apical pulp of human deciduous teeth with immature apex
2021, Tissue and CellCitation Excerpt :Isolation of high-quality human postnatal stem cells from accessible sources is an important goal for tissue engineering. With high proliferation and multipotent differentiation capacity, stem cells derived from dental tissues are ideal seeding cells for the reconstruction of dental tissue (Li et al., 2019; Morsczeck and Reichert, 2017; Park et al., 2016; Zhai et al., 2018). To date, several types of stem cells from dental tissues have been isolated and characterized, including dental pulp stem cells (DPSCs) (Gronthos et al., 2000), stem cells from exfoliated deciduous teeth (SHED) (Chen et al., 2014; Miura et al., 2003), periodontal ligament stem cells (PDLSCs) (Seo et al., 2004), dental follicle progenitor cells (DFPCs) (Morsczeck et al., 2005), stem cells from apical papilla (SCAP) (Chen et al., 2013; Huang et al., 2008; Sonoyama et al., 2006, 2008) and periodontal ligament stem cells from human retained deciduous teeth (DePDLSCs) (Ji et al., 2013).
Calreticulin as a special marker to distinguish dental pulp stem cells from gingival mesenchymal stem cells
2021, International Journal of Biological MacromoleculesCitation Excerpt :Adult stem cells are considered a convenient and available material in regenerative medicine because there is no ethics issues [1]. Dental stem cells have been proven to illustrate a variety of capabilities, including the potential for high proliferation, multi-lineage differentiation and immunosuppression [2]. Stem cells isolated from teeth have shown potential applications in dental pulp regeneration, type1diabetes, bone tissue engineering, periodontal repair and nerve regeneration [3].
Treated dentin matrix‐based scaffolds carrying TGF-β1/BMP4 for functional bio-root regeneration
2020, Applied Materials TodayCitation Excerpt :Recently, although various strategies like stem cell-based bioengineering [1, 2], bioengineered tooth germ [3] and tissue-engineering approach [4] have made huge improvements in the biological regeneration of teeth, the goal of functional teeth has not been achieved yet [1, 5].
Revitalizing mouse diphyodontic dentition formation by inhibiting the sonic hedgehog signaling pathway
2022, Developmental Dynamics3D Printing—A Way Forward
2022, Dental Implants and Oral Microbiome Dysbiosis: An Interdisciplinary Perspective