Biomimetic Restoration of Tooth Dentin via Deep Mineralization

Project Information

REDEEM

Grant agreement ID: 101029653

DOI

10.3030/101029653

Project closed

EC signature date 19 March 2021

Start date 1 April 2021

End date 2 October 2023

Funded under

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Total cost

€ 157 355,52

EU contribution

€ 157 355,52

Coordinated by

IZMIR INSTITUTE OF TECHNOLOGY
Türkiye

Periodic Reporting for period 1 - REDEEM (Biomimetic Restoration of Tooth Dentin via Deep Mineralization)

Reporting period: 2021-04-01 to 2023-03-31

Summary of the context and overall objectives of the project

The REDEEM project addresses the issue of demineralization, the loss of minerals from dental hard tissues, which remains a global risk affecting approximately 3.5 billion people. Despite the decline in dental cavities due to fluoride use, conditions related to demineralization, particularly dentin hypersensitivity (DH), impact over 50% of the adult population. DH lacks a permanent solution, and the ideal treatment should replicate a well-integrated mineral layer, emulating the protective enamel and cementum tissues to cover and seal exposed tubules.

The REDEEM project's overarching objective is to introduce a groundbreaking method termed "Deep Mineralization" for the biomimetic restoration of exposed dentin, achieving lasting durability. This involves four key objectives: (i) Experimental selection of peptides through Deep Directed Evolution, combining directed evolution with next-generation sequencing to generate quantitative peptide datasets (big data); (ii) Utilization of a machine learning-based predictive design platform, BioMInt, to develop protein-derived peptides. This platform is trained with big data and refined through (iii) High-throughput (HTP) validation assays; and ultimately, (iv) Establishment of a peptide-guided remineralization methodology (Deep Mineralization). This method mimics saliva's remineralization action, where peptides derived from enamel and cementum-related proteins bind to exposed dentin, recruit calcium and phosphate ions, and synthesize an integrated mineral layer. This process seals exposed dentin tubules by penetrating into them, effectively restoring the tooth's natural protection.

Beyond its immediate application to dentin hypersensitivity, Deep Mineralization holds promise for broader dental health. Its adaptability and scalability make it a potential asset in routine dental care practices, addressing not only DH but also contributing to preventive dentistry on a larger scale. This scalability aligns with our vision for the project's future implications, envisioning a transformative impact on dental research, potential commercialization avenues, and the advancement of preventive measures in oral healthcare.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

Over the course of the project, our primary focus has been to address the global issue of demineralization in dental hard tissues, particularly dentin hypersensitivity (DH). Our project, centered around the pioneering 'Deep Mineralization' method, has made significant strides in the biomimetic restoration of exposed dentin.

Key project activities included the experimental selection of peptides through Deep Directed Evolution, combining directed evolution with next-generation sequencing to generate extensive quantitative peptide datasets, often referred to as big data. Utilizing the machine learning-based predictive design platform, BioMInt, we successfully developed protein-derived peptides, refining our approach through high-throughput validation assays.

A milestone achievement of the project is establishing a peptide-guided remineralization methodology, Deep Mineralization. This innovative method mimics saliva's natural remineralization action, effectively sealing exposed dentin tubules by synthesizing an integrated mineral layer. Our recent publication, alongside several others, highlights the successful development of a peptide-based remineralization procedure. This procedure, demonstrated on extracted human teeth, showcases peritubular mineralization, ensuring structural, chemical, and thermal stability.

Looking beyond its immediate application to dentin hypersensitivity, Deep Mineralization holds promise for broader dental health. Its adaptability and scalability position it as a valuable asset in routine dental care practices, contributing not only to DH treatment but also to preventive dentistry on a larger scale.

As we reflect on the completed project timeline, marked by key milestones and achievements, our unwavering commitment remains towards realizing the ultimate goal of Deep Mineralization. The successful development of a practical and permanent solution for dentin hypersensitivity, as evidenced by our recent publication, marks a significant contribution to global dental health. Moving forward, we anticipate the transformative impact of our research on dental practices, potential commercialization avenues, and the advancement of preventive measures in oral healthcare.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

Through our project, we have achieved progress beyond the current state of the art in dental care by introducing the innovative 'Deep Mineralization' method. Unlike existing treatments, this approach aims to provide a comprehensive and lasting solution to dentin hypersensitivity, replicating the protective enamel and cementum tissues.

Moving forward, we anticipate further advancements until the conclusion of the project. The expected results include refining and optimizing the Deep Mineralization method, ensuring its effectiveness in diverse clinical scenarios. Additionally, we aim to expand our understanding of the socio-economic impact of our research, considering its potential to reduce healthcare costs associated with dental issues and enhance overall societal well-being.

The socio-economic impact of our project is multifaceted. By addressing dentin hypersensitivity and demineralization on a global scale, we envision a positive economic effect stemming from reduced dental care expenditures and improved productivity resulting from enhanced oral health. Moreover, the widespread applicability of the Deep Mineralization method in routine dental care practices has the potential to alleviate the societal burden posed by dental ailments.

Beyond economic considerations, the societal implications of our project are substantial. The availability of an effective, scalable, and preventive solution for dentin hypersensitivity not only enhances individual quality of life but also contributes to the broader goal of preventive dentistry. This aligns with our vision for societal well-being, where improved oral health can positively influence overall health outcomes and contribute to a more robust and resilient society.

In summary, our project has surpassed the current state of the art in dental care by introducing the Deep Mineralization method. As we progress, we aim to refine this method, expecting significant positive impacts on socio-economic factors and societal well-being. The project's potential lies not only in its innovative approach to dentin hypersensitivity but also in its broader implications for preventive dentistry and overall public health.

Graphical Abstract of REDEEM - Repair of Dentin via Deep Mineralization