Novel Antibacterial Fluoride-releasing Dental Materials

描述（由申请人提供）：我们建议研究和开发具有抗菌和/或氟释放作用的新型牙科材料，并协同作用以形成高效的龋抑制修复系统。这些材料预计将对人口中最脆弱、最易患龋齿的部分人群的口腔健康产生巨大影响：患有口干或口干（由于干燥综合征、糖尿病、头颈部照射和药物）的医疗受损者、儿童、老年人和社会经济地位较低的群体。龋齿仍然是一种世界性的流行病。虽然树脂基牙科复合材料（RBC）被广泛用于修复龋齿，但继发性（复发性）龋齿仍然是替代它们的主要原因。因此，人们一直致力于开发能够释放龋齿预防剂（如氟化物）的复合材料。然而，目前的牙科复合材料缺乏氟化物释放和氟化物补充的能力，很少有抗菌或其他防止菌斑的能力。此外，所有牙科复合材料和复合材料都需要粘合剂，以减少边缘泄漏和限制继发性龋齿。然而，不释放氟化物和低释放氟化物的粘结剂都是阻碍氟化物进入易患龋齿地区的内在障碍。另一个问题是，大多数自蚀刻牙粘接剂易被水解降解，从而导致最终的渗漏、继发性龋齿和红细胞寿命缩短。在预防初级龋齿方面，包括释放氟化物的密封剂在内的密封剂已经显示出预防龋齿的功效，但牙科行业采用密封剂的速度很慢，部分原因是担心龋齿会在封闭的牙槽和牙缝下继续发展。该项目的目标是开发具有增强抗菌活性、增强氟化物释放和补充以及其他能力的新型单体，并将其与释放氟化物的填料和生物活性填料结合起来，以克服当前复合材料、粘合剂和密封剂限制其抑龋效果和修复寿命的多重问题。本项目有四个具体目标：(1)制备并优化一种新型抗菌释氟口腔复合材料；(2)制备并优化一种新型水解稳定释氟口腔粘结剂；(3)制备并表征一种新型抗菌释钙、释磷、释氟生物活性密封胶；(4)通过人工龋齿模型测试新型抗龋齿材料体系的整体抑牙效果。假设是：(1)含有新的氟化物交换单体的牙科材料将增强氟化物的释放和补充能力，同时保持足够或改善的物理和机械性能。(2)抗菌活性与增强的再矿化能力相结合，可显著提高修复材料的抑龋效果。(3)抗菌氟释放复合材料、粘结剂和生物活性密封剂的联合使用将进一步减少龋齿。本项目旨在开发一系列抗菌、氟释放和生物活性牙科材料。这些材料有望比现有的树脂基牙科材料具有更强的抗龋功效。这些材料的开发有可能对口腔保健和口腔健康生活质量产生巨大影响，特别是对大量高龋风险患者（患有口干或口干的医学上受损的患者、儿童、老人、智力或身体有问题的人）。

DESCRIPTION (provided by applicant): We propose to investigate and develop novel dental materials that are antibacterial and/or fluoride-releasing and act synergistically to form a highly effective caries-inhibition restorative system. Such materials are expected to have an enormous impact on the oral health of the most vulnerable, high caries-risk, portion of the population: the medically-compromised who suffer from xerostomia or dry mouth (due to Sjvgren's syndrome, diabetes, head and neck irradiation, and medications), children, the elderly, and low socio-economic groups. Dental caries continues to be a worldwide pandemic disease. While resin-based dental composites (RBC) are widely used to restore carious teeth, secondary (recurrent) caries remains the leading cause cited for their replacement. Thus, much effort has been directed towards development of composites that release caries-preventing agents such as fluoride. Nevertheless, current dental composites are deficient in both fluoride-release and fluoride-recharge capabilities, and very few have antimicrobial or other capabilities for preventing plaque. Furthermore, all dental composites and compomers require bonding agents in order to reduce marginal leakage and limit secondary caries. Yet, both non-fluoride-releasing and low-fluoride-releasing bonding agents are inherently barriers to the transport of fluoride to caries-prone areas. Another problem is that the majority of self-etching dental bonding agents are susceptible to hydrolytical degradation, which leads to eventual leakage, secondary caries and reduced RBC lifetime. On the primary caries prevention front, sealants, including fluoride-releasing sealants, have shown caries-prevention efficacy, yet the dental profession has been slow to adopt sealants due, in part, to the fear that caries will continue to progress under sealed pits and fissures. The goal of this project is to develop novel monomers with enhanced antibacterial activity, enhanced fluoride release and recharge, and other capabilities, and combine them with fluoride-releasing fillers and bioactive fillers to overcome the multiple problems associated with current composites, adhesives and sealants that limit their caries-inhibition efficacy and restoration longevity. This project has four specific aims: (1) to formulate and optimize a novel antibacterial fluoride releasing dental composite, (2) to formulate and optimize a novel hydrolytically stable fluoride-releasing dental bonding agent, (3) to formulate and characterize a novel antibacterial bioactive sealant that releases calcium, phosphate, and fluoride, (4) to test the overall caries-inhibition efficacy of the novel anticariogenic dental material system by artificial caries models. The hypotheses are: (1) Dental materials containing the new fluoride exchange monomers will have enhanced fluoride release and recharge capabilities while maintaining adequate or improved physical and mechanical properties. (2) The combination of antimicrobial activity with enhanced remineralization capability will synergistically lead to significantly higher caries-inhibiting efficacy of the restorative materials. (3) The combined use of an antibacterial fluoride-releasing composite, bonding agent and bioactive sealant will further reduce caries. This project seeks to develop a series of antibacterial, fluoride-releasing, and bioactive dental materials. These materials are expected to have enhanced anti-caries efficacy over existing resin-based dental materials. The development of these materials has the potential to make a huge impact on oral health care and oral health quality-of-life, in particular for the vast number of high-caries-risk patients (medically compromised who suffer from xerostomia or dry mouth, children, elderly, mentally or physically challenged).