Zinc nanocrystals from zinc tetraammine fluoride for caries arrest and remineralization

Abstract The WHO estimated that oral diseases affect close to 3.5 billion people worldwide, with 3 out of 4 people affected living in middle-income countries. Untreated dental caries affects about 2.5 billion people, and children affected with dental caries have a much higher risk of continued disease burden in their later life. Coined the “silent epidemic”, the National Institute of Dental and Craniofacial Research estimates that over 40% of US children aged 2-11 have experienced caries and untreated caries affects more than 20%. Treating dental caries requires equipment, materials and a setting that require significant expenditures which represent a burden to the individual, the community and the system. Currently silver diamine fluoride (SDF) is a gold standard for managing caries lesions in young children, adults, and those with special care needs. However, a major downside of SDF is that the precipitation of silver byproducts in the dental tissues stain the lesions black, and in many cases considered unacceptable. Concern about silver toxicity further limits it use in caries management. In this Phase I study we want to develop and test zinc tetraammine difluoride [Zn(NH3)4]F2, referred to below as ZAF, a precursor to nanocrystals of ZnO and Zn(OH)F that can be deposited for caries arrest and remineralization. Our preliminary data showed that Zn formulations have strong antibacterial activity against oral pathogens including Streptococcus mutans and ZAF deposits a uniform coating on peritubular dentin as a robust potential nanocrystalline antimicrobial film. The objective of this Phase I study is to provide ZAF as a non-invasive, aesthetically accepted, and cost-effective practical alternative to the traditional management strategies for dental caries. In Aim 1 we will determine the mineral loading efficacy of ZAF agents in human dentin using permanent human molars, with and without carious lesions. In Aim 2 we will determine the antibacterial property of ZAF against caries pathogens using multi-species biofilms. Achieving the stated milestones of this proposal will allow us to develop ZAF as an aesthetically pleasing and cost effective dental material for restoration and cosmetic dentistry with the preservation of natural tooth structure and color. The global dental caries treatment market was valued at US$ 6.3 B in 2021 and is forecast to reach a value of US$ 8.6 B by 2028.The strategic partnership of Periomics Care LLC, NYU Chemistry Department and SDI Limited, a world leader in specialist dental materials will be well poised to address this strong growth of market demand due to the increasing population suffering from dental caries.