We are pleased to introduce the collection Frontiers in Dental Medicine: Highlights in Regenerative Dentistry 2021/22. This collection will welcome and showcase a selection of high impact articles authored by leaders in the field. The work presented here highlights the broad diversity of research performed across the Regenerative Dentistry section, and aims to put a spotlight on the main areas of interest. This collection aims to further support Frontiers’ strong community by shining a spotlight on our authors' highly impactful research.

The University of Hong Kong

Explore groundbreaking research in Regenerative Dentistry across Frontiers' Dental Medicine community.

. This research topic explores the advances in tooth development and regeneration, focusing on the biological properties and interactions of dental biomaterials used in vital pulp treatment procedures. It also looks at the awareness, understanding, and beliefs about Regenerative Dentistry (RD) of active dentists in the UK. The key findings include: <ul> <li>The Wnt signaling pathway plays a critical role in postnatal tooth root development and tooth eruption, and its proper expression is essential for the formation and eruption of teeth.</li> <li>Synthetic peptides P26 and P32 incorporated into chitosan hydrogel were tested for their efficacy in remineralizing enamel decay, with increased stability in vitro and improved mechanical properties.</li> <li>Active dentists are aware of the field but are not prepared to apply personalized biologically based therapies and need further education.</li> </ul>

Frontiers in Dental Medicine

Regenerative Dentistry

Frontiers in Dental Medicine: Highlights in Regenerative Dentistry 2021/22

Editorial on the Research Topic <a href="https://www.frontiersin.org/research-topics/33042/frontiers-in-dental-medicine-highlights-in-regenerative-dentistry-202122#articles">Frontiers in Dental Medicine: highlights in regenerative dentistry 2021/22</a>According to the global oral health status report issued by WHO for 2022, oral diseases are the most widespread noncommunicable diseases affecting almost half of the world&apos;s population (45% or 3.5 billion people worldwide) over the life course from early life to old age. The traces of the prevalence of caries and periodontal disease run into ancient times, but the complete rehabilitation of caries or periodontal disease-affected tissues is yet to be achieved. Current treatment options offer to control the disease process to obtain symptomatic relief or/and restoration of tissue by artificial materials. As adult human teeth are not replaced naturally, it is necessary to find ways to achieve a fully functional recovery of teeth affected by oral diseases and conditions. Regenerative dentistry aims to regenerate injured or diseased tissue or the whole functional dental organ using biologically based approaches. The current Research Topic highlights some of the important advancements in regenerative dentistry.Tooth development is a very important area of research that provides valuable insight into regenerative dentistry. Studying tooth development is necessary for unraveling the molecular mechanisms in development and using this knowledge in tooth regeneration. For example, Wnt signaling is one of the important pathways in tooth development. The importance of Wnt signaling in proper tooth development is emphasized in two review articles in the Research Topic that together, comprehensively, cover its role in tooth development, root formation, periodontal ligament, and bone, concluding with potential clinical applications of the modulation of this pathway. In the review by <a href="https://doi.org/10.3389/fdmed.2021.769134">Tokavanich&nbsp;et al.</a> they emphasized that the proper expression of Wnt signaling during dental development is crucial for regulating cellular proliferation and differentiation as well as the epithelial-mesenchymal interaction essential for tooth root formation and tooth eruption. Accordingly, Wnt signaling plays a major role in the response of odontoblasts to injury and repair processes. It is also directly linked to the healing and repair process that is fundamental to recovering oral tissues affected by the inflammatory process and recovery for regeneration. The review by <a href="https://doi.org/10.3389/fdmed.2021.725468">Birjandi and Sharpe</a> from Kings College London explores how the Wnt signaling pathway could be utilized to enhance regenerative approaches by promoting healing and repair.Biomaterials play a major role in carrying the signaling mediators or cells to the target host tissue. Various biomaterials encapsulated with biomolecules or cells have been utilized in regenerative approaches and demonstrated positive results in&nbsp;vitro and in vivo. Some of these approaches are currently in phase I/II clinical trials on evaluating their safety and efficacy. In our Research Topic, groups from the University of Southern California and Johns Hopkins University, Baltimore, presented a study where amelogenin-derived peptides P26 and P32 incorporated chitosan hydrogel that was fabricated for the remineralization of the enamel, which is a fundamental requirement for the regeneration of a complete tooth structure. <a href="https://doi.org/10.3389/fdmed.2021.697544">Mukherjee et al.</a> reported that P26 peptide alone or in combination with chitosan significantly enhanced the remineralization of the enamel. The ability to regrow tooth enamel could be a major step in the functional recovery of the tooth structure.Various enhancements in the field of regenerative dentistry have raised enthusiasm among clinical dental practitioners to utilize these advances in their practice. However, the study conducted by <a href="https://doi.org/10.3389/fdmed.2021.630546">Neves and Jamal</a> from Kings College London among practicing dentists in the UK demonstrated that there is a bigger knowledge gap between clinicians and researchers on the potential applications of regenerative dentistry. As a result, some dentists are still skeptical about applying these therapies in the clinical field which emphasizes the need to transfer knowledge from benchtop to the clinic. Most dentists have the desire to educate themselves more on the advances of regenerative dentistry and how they could utilize them in their practice. Therefore, it is the need of the hour of the regulatory and educational bodies to corporate and make a clear consensus to enhance the knowledge of regenerative dentistry among dentists as well as dental students.Both authors listed have made direct and intellectual contributions to the manuscript and approved it for publication. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author PS declared that he was an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

Editorial: Frontiers in Dental Medicine: highlights in regenerative dentistry 2021/22

Appropriate tooth root formation and tooth eruption are critical for achieving and maintaining good oral health and quality of life. Tooth eruption is the process through which teeth emerge from their intraosseous position to their functional position in the oral cavity. This temporospatial process occurs simultaneously with tooth root formation through a cascade of interactions between the epithelial and adjoining mesenchymal cells. Here, we will review the role of the Wnt system in postnatal tooth root development. This signaling pathway orchestrates the process of tooth root formation and tooth eruption in conjunction with several other major signaling pathways. The Wnt signaling pathway is comprised of the canonical, or Wnt/β-catenin, and the non-Canonical signaling pathway. The expression of multiple Wnt ligands and their downstream transcription factors including β-catenin is found in the cells in the epithelia and mesenchyme starting from the initiation stage of tooth development. The inhibition of canonical Wnt signaling in an early stage arrests odontogenesis. Wnt transcription factors continue to be present in dental follicle cells, the progenitor cells responsible for differentiation into cells constituting the tooth root and the periodontal tissue apparatus. This expression occurs concurrently with osteogenesis and cementogenesis. The conditional ablation of β-catenin in osteoblast and odontoblast causes the malformation of the root dentin and cementum. On the contrary, the overexpression of β-catenin led to shorter molar roots with thin and hypo-mineralized dentin, along with the failure of tooth eruption. Therefore, the proper expression of Wnt signaling during dental development is crucial for regulating the proliferation, differentiation, as well as epithelial-mesenchymal interaction essential for tooth root formation and tooth eruption.

Appropriate tooth root formation and tooth eruption are critical for achieving and maintaining good oral health and quality of life. Tooth eruption is the process through which teeth emerge from their intraosseous position to their functional position in the oral cavity. This temporospatial process occurs simultaneously with tooth root formation through a cascade of interactions between the epithelial and adjoining mesenchymal cells. Here, we will review the role of the Wnt system in postnatal tooth root development. This signaling pathway orchestrates the process of tooth root formation and tooth eruption in conjunction with several other major signaling pathways. The Wnt signaling pathway is comprised of the canonical, or Wnt/&#x3b2;-catenin, and the non-Canonical signaling pathway. The expression of multiple Wnt ligands and their downstream transcription factors including &#x3b2;-catenin is found in the cells in the epithelia and mesenchyme starting from the initiation stage of tooth development. The inhibition of canonical Wnt signaling in an early stage arrests odontogenesis. Wnt transcription factors continue to be present in dental follicle cells, the progenitor cells responsible for differentiation into cells constituting the tooth root and the periodontal tissue apparatus. This expression occurs concurrently with osteogenesis and cementogenesis. The conditional ablation of &#x3b2;-catenin in osteoblast and odontoblast causes the malformation of the root dentin and cementum. On the contrary, the overexpression of &#x3b2;-catenin led to shorter molar roots with thin and hypo-mineralized dentin, along with the failure of tooth eruption. Therefore, the proper expression of Wnt signaling during dental development is crucial for regulating the proliferation, differentiation, as well as epithelial-mesenchymal interaction essential for tooth root formation and tooth eruption.

The Role of Wnt Signaling in Postnatal Tooth Root Development

Teeth are complex structures where a soft dental pulp tissue is enriched with nerves, vasculature and connective tissue and encased by the cushioning effect of dentin and the protection of a hard enamel in the crown and cementum in the root. Injuries such as trauma or caries can jeopardise these layers of protection and result in pulp exposure, inflammation and infection. Provision of most suitable materials for tooth repair upon injury has been the motivation of dentistry for many decades. Wnt signalling, an evolutionarily conserved pathway, plays key roles during pre- and post-natal development of many organs including the tooth. Mutations in the components of this pathway gives rise to various types of developmental tooth anomalies. Wnt signalling is also fundamental in the response of odontoblasts to injury and repair processes. The complexity of tooth structure has resulted in diverse studies looking at specific compartments or cell types of this organ. This review looks at the current advances in the field of tooth development and regeneration. The objective of the present review is to provide an updated vision on dental biomaterials research, focusing on their biological properties and interactions to act as evidence for their potential use in vital pulp treatment procedures. We discuss the outstanding questions and future directions to make this knowledge more translatable to the clinics.

Teeth are complex structures where a soft dental pulp tissue is enriched with nerves, vasculature and connective tissue and encased by the cushioning effect of dentin and the protection of a hard enamel in the crown and cementum in the root. Injuries such as trauma or caries can jeopardise these layers of protection and result in pulp exposure, inflammation and infection. Provision of most suitable materials for tooth repair upon injury has been the motivation of dentistry for many decades. Wnt signalling, an evolutionarily conserved pathway, plays key roles during pre- and post-natal development of many organs including the tooth. Mutations in the components of this pathway gives rise to various types of developmental tooth anomalies. Wnt signalling is also fundamental in the response of odontoblasts to injury and repair processes. The complexity of tooth structure has resulted in diverse studies looking at specific compartments or cell types of this organ. This review looks at the current advances in the field of tooth development and regeneration. The objective of the present review is to provide an updated vision on dental biomaterials research, focusing on their biological properties and interactions to act as evidence for their potential use in vital pulp treatment procedures. We discuss the outstanding questions and future directions to make this knowledge more translatable to the clinics.

Wnt Signalling in Regenerative Dentistry

We designed synthetic peptides that have demonstrated an effective remineralization potential to restore incipient enamel decay. In order to develop a clinically viable approach we incorporated the amelogenin-derived peptides P26 and P32 into chitosan hydrogel and examined their efficacy in the remineralization of enamel. Peptides in chitosan exhibited increased stability in vitro as compared to peptides in solution at room temperature and at 37°C. Tooth models for enamel erosion (sections) and white spot lesions (blocks) were subject to periods of demineralization. Treatment groups were subjected to remineralization in artificial saliva in the presence of P26 and P32 in solution and in chitosan hydrogel (P26-CS and P32-CS). Quantitative light-induced fluorescence (QLF) was employed to analyze mineral density following demineralization and remineralization across all the treatment groups. Scanning electron microscopy and nanoindentation were used to characterize the surface structure and mechanical strength of regrown enamel. Control enamel sections treated in artificial saliva demonstrated randomly distributed, tiny, needle-shaped crystals with a low packing density and porosities displaying mineralization defects. In samples treated with P26-CS or P32-CS a denser coating of organized hydroxyapatite (HAP) crystals was formed covering the entire surfaces of demineralized enamel window. The hardness and modulus of enamel surfaces were increased after treatment with P26-CS and P32-CS with no significant difference in the mechanical properties between the two peptide hydrogels. Analysis of mineral density by QLF showed that in enamel sections P26 peptide alone or P26-CS significantly enhanced the remineralization. In enamel blocks P26 in solution had a better efficacy than P26-CS.

We designed synthetic peptides that have demonstrated an effective remineralization potential to restore incipient enamel decay. In order to develop a clinically viable approach we incorporated the amelogenin-derived peptides P26 and P32 into chitosan hydrogel and examined their efficacy in the remineralization of enamel. Peptides in chitosan exhibited increased stability in vitro as compared to peptides in solution at room temperature and at 37°C. Tooth models for enamel erosion (sections) and white spot lesions (blocks) were subject to periods of demineralization. Treatment groups were subjected to remineralization in artificial saliva in the presence of P26 and P32 in solution and in chitosan hydrogel (P26-CS and P32-CS). Quantitative light-induced fluorescence (QLF) was employed to analyze mineral density following demineralization and remineralization across all the treatment groups. Scanning electron microscopy and nanoindentation were used to characterize the surface structure and mechanical strength of regrown enamel. Control enamel sections treated in artificial saliva demonstrated randomly distributed, tiny, needle-shaped crystals with a low packing density and porosities displaying mineralization defects. In samples treated with P26-CS or P32-CS a denser coating of organized hydroxyapatite (HAP) crystals was formed covering the entire surfaces of demineralized enamel window. The hardness and modulus of enamel surfaces were increased after treatment with P26-CS and P32-CS with no significant difference in the mechanical properties between the two peptide hydrogels. Analysis of mineral density by QLF showed that in enamel sections P26 peptide alone or P26-CS significantly enhanced the remineralization. In enamel blocks P26 in solution had a better efficacy than P26-CS.

Amelogenin Peptide-Chitosan Hydrogel for Biomimetic Enamel Regrowth

Innovation has always been part of dentistry and with that comes thinking outside the box to produce guidelines for implementation of new approaches. Regenerative dentistry (RD) is a young specialty within the profession, which gathers knowledge from stem cells, molecular biology, and tissue and material engineering to produce and apply novel biologically based therapies. Since RD is an emerging branch of dentistry, it is not yet understood whether active clinicians are aware of this field and know exactly what it does. The aim of this study is to explore the awareness, understanding, and beliefs about RD of active dentists. A random selection of active dentists in the UK was approached via e-mail and face-to-face and asked to fill in a questionnaire. A total of 45 responses were received and analyzed. The results showed that active dentists in the UK are aware of the field but are not prepared to apply personalized biologically based therapies and feel a desire to educate themselves about RD further. Also, the results shine a light on the opportunities for regulatory and educational bodies to work together to prepare the clinicians for this novel field. Our research suggests that active dentists are ill-prepared for an era of personalized biologically based dental treatments. Further thinking of how to implement basic and more advanced biological knowledge and their application in dentistry is needed, and suggestions are made here.

Innovation has always been part of dentistry and with that comes thinking outside the box to produce guidelines for implementation of new approaches. Regenerative dentistry (RD) is a young specialty within the profession, which gathers knowledge from stem cells, molecular biology, and tissue and material engineering to produce and apply novel biologically based therapies. Since RD is an emerging branch of dentistry, it is not yet understood whether active clinicians are aware of this field and know exactly what it does. The aim of this study is to explore the awareness, understanding, and beliefs about RD of active dentists. A random selection of active dentists in the UK was approached via e-mail and face-to-face and asked to fill in a questionnaire. A total of 45 responses were received and analyzed. The results showed that active dentists in the UK are aware of the field but are not prepared to apply personalized biologically based therapies and feel a desire to educate themselves about RD further. Also, the results shine a light on the opportunities for regulatory and educational bodies to work together to prepare the clinicians for this novel field. Our research suggests that active dentists are ill-prepared for an era of personalized biologically based dental treatments. Further thinking of how to implement basic and more advanced biological knowledge and their application in dentistry is needed, and suggestions are made here.