NIDCR Strategies to Advance Novel Therapies and Treatments for Dental Structures Think Tank Summary: Remineralization

Date of Event: September 8, 2022, 1:00 p.m.–5:00 p.m. (EST)

Points of Contact

Background and Objectives

NIDCR convened a two-day virtual Think Tank with a diverse panel of experts representing multiple domain areas to discuss the most critical and challenging questions on Strategies to Advance Novel Therapies and Treatments for Dental Structures, representing areas of high priority investment for NIDCR. The Think Tank utilized an open discussion format on Key Themes in dental restoration and tooth structure remineralization. Enamel has a complex crystal microstructure formed slowly over an extended period of time, and is devoid of cellular support when mature making it difficult to restore. Thus, remineralization towards sound tooth structure is more beneficial before extensive decay and cavitation occur requiring more extensive restorations. Established (fluoride, hydroxyapatite) and novel therapies (e.g., polymer-induced) are ready for use and need to be encouraged especially for early stages of caries where the process can be reversed. This Think Tank examined ways other fields can inform mineralization of dental hard tissues, how the de- and re-mineralization process needs to be studied in the context of the oral environment, and how behavior of practitioners and patients affect implementation and adoption of these novel therapies and treatments.

Key Themes and Recommendations

What are major gaps and challenges to improve delivery of currently available or design of new remineralization solutions for teeth in the early stages of caries (ICDAS codes 0-3)?

Challenges

• Need for improvement of delivery of solutions that involves early detection through promotion of screening programs, which is key for successful intervention.
• Need to understand first how enamel is constructed into its fine self-assembly of crystalline structure.
• Cannot readily “watch” the growth of enamel in vivo.

Opportunities

• Develop interventions to explore and exploit the potential of remineralizing peptides and systems, improving technologies for increased penetration depth (e.g., electrophoretic migration).
• Develop affordable over-the-counter homecare products, to address challenges to early stages of caries lesions including prevalent developmental hypomineralization defects.
• Develop and/or adopt technology that can image and provide new information and add new dimensions on the various scales of enamel structure.

What are the major considerations of existing tooth structures of enamel and dentin for remineralization in an oral environment that need to be addressed?

Challenges

• Enamel and dentin are structurally different and require tailored strategies to each tissue.
• Simple mineral precipitation is distinct from biomimetic remineralization.
• Physicochemical properties and spatiotemporal dynamics of biointerfaces exist across multiple length scales.

Opportunities

• Include understanding of the dynamics of the biofilm-enamel-saliva interfaces in the oral environment, understanding chemical gradients at ultrastructural levels, considering different protocols for dentin and enamel remineralization and for patients across the lifespan, and standardizing laboratory study protocols and assays.
• Exploit the natural potential of dentin to improve remineralization techniques.
• Understand the mineralization processes of other organisms in order to learn and potentially apply them clinically.

What can we learn from other fields that can contribute to our knowledge of remineralizing human teeth with natural or non-toxic materials?

Challenges

• Work in other fields (e.g., self-healing concrete) needs to be leveraged to apply to the dental context of secondary caries and remineralization.
• Engineering and fundamental molecular techniques (e.g., mechanochemistry, force spectroscopy) needs to be adopted in the dental space.
• Remineralizing claims will likely require FDA consideration of designation and traverse the regulatory framework.

Opportunities

• Enhance the dialogue between dental clinicians and basic scientists.
• Define attainable goals (and/or products) for basic and translational scientists.
• Employ in vivo-like models, identify common cellular/molecular regulators of biomineralization that could be used/targeted to enhance remineralization.
• Increase clarification of the FDA regulatory pathway regarding the classification of remineralization agents (medical devices vs. drugs).

What technical and implementation challenges are preventing practitioners and patients from adoption or getting the field where it could be?

Challenges

• Diagnostic tools of high sensitivity, specificity, and accuracy, and outcome measures to accurately capture structure and function of remineralized tissues are needed.
• Patients often seek dental care primarily for treatment dental diseases and pain.
• Dentistry relies heavily on key opinion leaders to adopt innovations.
• Translating discoveries to clinical applications is a long process.

Opportunities

• Build the research community through experienced translational entities that individual investigators can tap into and that can facilitate translation-driven science, and ones that can also educate investigators about translation across the sectors.
• Educate academic research faculty on pathways turning discoveries into clinical care products, e.g., technology transfer, market assessment, commercialization.
• Partner and leverage translational initiatives across NIH; facilitate public-private partnerships; team up to seek early regulatory guidance; and incorporate "Reverse translation" driven by unmet clinical needs.
• Consider a multi-parametric approach to involve patient characteristics and specific needs.
• Address potential questions that arise surrounding safety, durability, and cost that impact form, function, esthetics, and cost-effectiveness; care delivery models; underserved populations; connectedness of systemic and oral health; reimbursement models; environment stewardship; and data-driven discovery.

Attendees

Jeanne Ambruster, B.A.
Chief Executive Officer
Avenues Company

Eric Anderson, Ph.D.
Chief Operating Officer
Mussel Polymers Inc.

Ana Bedran-Russo, D.D.S., Ph.D.
Professor and Chair - Department of General Dental Sciences
Marquette University

Smadar Ben-Tabou, Ph.D.
Professor, Department of Marine Biology
University of Haifa

Joseph DeSimone, Ph.D.
Sanjiv Sam Gambhir Professor of Translational Medicine and Chemical Engineering
Stanford University

Josephine Esquivel-Upshaw, D.M.D.
Professor, College of Dentistry
University of Florida

Bernhard Ganns, B.Sc., M.Sc., Ph.D.
Professor of Dentistry, Vice Dean, Research
University of Toronto School of Dentistry

Jason Griggs, Ph.D.
Professor, Associate Dean for Research
University of Mississippi Medical Center

Mike Hubbard, D.D.S., Ph.D.
Professor, Division of Medicine, Dentistry and Health Sciences
Royal Children's Hospital, Melbourne Medical School

Sharukh Khajotia, D.D.S., M.S., Ph.D.
Associate Dean for Research and Innovation, College of Dentistry
University of Oklahoma Health Sciences Center

Hyun (Michel) Koo, D.D.S., M.S., Ph.D.
Founding Director, Center for Innovation & Precision Dentistry
Professor, Department of Orthodontics
University of Pennsylvania Dental Medicine

Deirdre Lyons, Ph.D.
Assistant Professor, Marine Biology
Scripps Institution of Oceanography

Tatjana Maravic, Ph.D.
Assistant Professor, Department of Biomedical and Neuromotor Sciences
University of Bologna, Italy

Phil Messersmith, Ph.D.
Chair of Bioengineering, Professor, Departments of Bioengineering and Materials Science and Engineering
University of California, Berkeley

Carmem Pfeifer, D.D.S., Ph.D.
Professor of Restorative Dentistry, School of Dentistry
Oregon Health & Science University

Kevin Rosso, Ph.D.
Laboratory Fellow and Associate Director of the Physical Sciences Division for Geochemistry
Pacific Northwest National Labs

Paulette Spencer, D.D.S., M.S., Ph.D.
Director, Institute for Bioengineering Research
Ackers Distinguished Professor, Mechanical Engineering
University of Kansas

Yu Zhang, Ph.D.
Professor, Division of Restorative Dentistry, Preventive & Restorative Sciences
University of Pennsylvania Dental Medicine