Restoration of non-cavitated carious lesions in enamel using nano-fluorapatite particles

Abstract: This project responds to the NIDCR mission to develop and translate knowledge about dental and oral health into treatment strategies that improve overall health for all individuals and communities across the lifespan. Worldwide, caries is the most common chronic disease affecting almost everyone. It is a major cause of economic and social loss and leads to complications including pain, tooth loss and even death. This progressive disease, when diagnosed before cavities have formed, can be treated non-restoratively. Fluoride has been successful in slowing carious lesion progression by reducing mineral loss and encouraging mineral gain in the surface of enamel lesions; however, it is not as efficacious in restoring mineral that was lost in the subsurface. Remineralizing treatments under development to target subsurface remineralization face the challenge of guiding precipitation of minerals inside caries lesions and require adequate conditions for mineral formation, which usually are not present under a high cariogenic challenge. Here we propose to halt the progressive demineralization cycle in dental caries not by a process of remineralization, but by filling the porous subsurface enamel directly with a more resistant, biomimetic material: fluorapatite (FA) particles. In preliminary data we demonstrate the ability of nanoscale FA (nFA) to penetrate through the more highly mineralized surface zone of in vitro produced and ex-in vivo white spot lesions and delivery into the subsurface porosities. This treatment would supersede contemporary remineralization agents which need multiple treatments over time to form mineral as part of their anticaries therapy. Our goal is to translate this innovative, yet simple, anticaries therapy into inexpensive over-the-counter products that will treat early lesions from the inside out, to stop their progression. The FA particles have a similar composition to the fluoride-containing hydroxyapatite of human tooth enamel with the enhanced property of reduced solubility in acid. FA particles have been shown to be: non-toxic; biocompatible; antibacterial; fluoride releasing at low pH; and bioactive in several in vitro studies. In this Phase I SBIR proposal, we intend to establish the feasibility of FA particles as an anticaries therapy by determining the ability of FA particles to penetrate demineralized porous subsurface enamel and restore natural apatitic structure, making the caries lesion more resistant to further demineralization, using in vitro caries models. Successful completion of the project aims will support the pre-clinical efficacy and benefits of FA particles as a caries treatment, which will de- risk future product development towards clinical validation and commercialization. Phase II will involve the incorporation of FA particle technology into an OTC formulation, determination of manufacturing scalability and scale-up to pilot level, regulatory strategy development, and additional preclinical and pilot clinical efficacy studies.