Feasibility of novel Fluorine Non-thermal plasma for dental caries control

龋齿是一种多因素的疾病，它是由牙齿生物膜、口腔粘膜、牙周膜和牙周膜之间的相互作用引起的。 环境和牙齿结构。文献中越来越多的报告表明，氟化物可以减少 釉质脱矿和促进釉质矿化，并在足够的浓度，可以抑制 由致龋细菌产生的酸。氟化物是预防龋齿的基石， 第一道防线。然而，尽管氟化物在牙科中广泛使用了几十年，龋齿仍然是一个严重的问题。 严重的全球公共卫生问题。当前氟化物输送技术的局限性包括低浓度。 递送的氟化物渗透到表面下区域和递送的氟化物在牙齿上的短期保留， 这妨碍了氟化物的充分利用。然而，F技术的进步很少， 过去几十年来，克服这些限制。 我们的灵感来自于报道，氟非热等离子体（FNTPs）产生的含氟饲料 气体可以产生游离的F原子（F-离子和F自由基），FNTPs已被用于合成 各种金属氟化物。我们在这一领域的开创性工作表明，FNTPs可以将氟化物输送到 牙釉质和提高其矿化使用在体外pH循环实验。此外，我们以前的 体外实验表明，Ar和Ar/O2低温等离子体（NTPs）都能有效地降低S。 变形链球菌细胞和S.变形菌生物膜形成。我们在雌性Sprague-Dawley大鼠中的体内研究表明， 用2分钟Ar/O2等离子体处理的磨牙在等离子体处理后6个月显示出较少的龋齿表面 相对于未处理的磨牙，上磨牙减少62.5%，下磨牙减少31.6%。 在这个应用中，我们提出了生物相容性FNTPs，并研究其对牙齿的效率 牙釉质矿化、氟化物进入牙釉质和抑制牙齿生物膜的恢复， 目标是开发FNTPs以控制龋齿。我们的中心假设是生物相容性FNTPs 由等离子体进料气体产生，所述等离子体进料气体包括氩气（Ar）气体和无毒且无刺激性的含F 气态化合物将具有通过有效氟化增强矿化的双重效果， 抑制生物膜恢复。设计了两个具体目标来检验这一假设。具体目标1： 具有理想氟化物输送能力的生物相容性FNTPs和具体目标2，以评估 FNTP处理对促进釉质矿化、氟化物进入牙釉质的影响 牙釉质和体外牙生物膜恢复的抑制。该研究项目不仅将 有助于我们对FNTP生成及其与牙釉质和牙本质相互作用的基础知识 生物膜，而且还促进FNTPs的发展，作为预防和早期 治疗龋齿，从而对控制这一对人类健康的重大危害产生重大影响。

Dental caries represents a multifactorial disease that results from interactions among dental biofilms, the oral environment, and tooth structure. Mounting reports in the literature demonstrated that fluoride could decrease enamel demineralization and enhance enamel remineralization, and at sufficient concentrations, could inhibit acid production by cariogenic bacteria. Fluoride is the cornerstone for dental caries prevention and remains its first line of defense. Yet despite the extensive use of fluoride in dentistry for decades, dental caries remains a serious public health problem worldwide. Limitations of current fluoride delivery technologies include low penetration of delivered fluoride into sub-surface areas and short-term retention of delivered fluoride on teeth, which prevent the full utilization of fluoride. However, few advancements in F technologies have been made in past decades to overcome these limitations. We were inspired by reports that fluorine nonthermal plasmas (FNTPs) generated from F-containing feed gases could produce free F atoms (F- ions and F free radicals) and that FNTPs have been used to synthesize various metal fluorides. Our pioneering work in this area has demonstrated that FNTPs can deliver fluoride into tooth enamel and enhance its remineralization using an in vitro pH cycling experiment. Moreover, our previous in vitro work demonstrated that both argon (Ar) and Ar/O2 nonthermal plasmas (NTPs) efficiently decrease S. mutans cells and S. mutans biofilm formation. Our in vivo study in female Sprague–Dawley rats showed that rat molars treated with 2-minute Ar/O2 plasmas exhibited less decayed tooth surfaces 6 months after the plasma treatment, 62.5% less on the upper molars and 31.6% less on the lower molars relative to untreated molars. In this application, we propose to generate biocompatible FNTPs and investigate their efficiencies on tooth enamel remineralization, fluoride delivery into enamel, and inhibition of dental biofilm recovery with the ultimate goal of developing FNTPs for control of dental caries. Our central hypothesis is that biocompatible FNTPs generated from a plasma feed gas comprised of argon (Ar) gas and a nontoxic and nonirritating F-containing gaseous compound will have the dual effects of enhancing remineralization via effective fluoridation and inhibiting biofilm recovery. Two specific aims are designed to test this hypothesis. Specific Aim 1, to generate biocompatible FNTPs with desirable fluoride delivery capabilities, and Specific Aim 2, to assess the effect and efficiency of FNTP treatment on enhanced remineralization of enamel, fluoride delivery into enamel, and inhibition of dental biofilm recovery in vitro. This proposed research project will not only contribute to our fundamental knowledge of FNTP generation and their interaction with tooth enamel and dental biofilms, but also facilitate the development of FNTPs as an innovative approach for prevention and early treatment of dental caries, thus producing a major impact in controlling this prominent hazard to human health.