Novel Antibacterial Fluoride-releasing Dental Materials

描述（由申请人提供）：我们计划研究和开发新型牙科材料，这些材料具有抗菌和/或氟化物释放性，并协同作用，形成高效的龋齿抑制修复系统。预计这些材料将对最脆弱、高龋齿风险人群的口腔健康产生巨大影响：患有口干症或口干（由于舍格伦综合征、糖尿病、头颈部照射和药物治疗）的医疗受损人群、儿童、老年人和低社会经济群体。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）龋齿仍然是其替换的主要原因。因此，许多努力都是针对开发释放防龋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再充电能力，并且很少有抗菌或其他预防牙菌斑的能力。此外，所有牙科复合材料和复合体都需要粘合剂，以减少边缘渗漏并限制继发性龋齿。然而，无论是非氟释放和低氟释放粘合剂本身的障碍，氟化物运输到龋齿易发地区。另一个问题是大多数自蚀刻牙科粘合剂易受水解降解的影响，这导致最终的渗漏、继发性龋齿和RBC寿命缩短。在初级龋齿预防方面，密封剂，包括释放氟化物的密封剂，已经显示出龋齿预防功效，但牙科专业人员采用密封剂的速度很慢，部分原因是担心龋齿在密封的窝沟和裂隙下会继续发展。该项目的目标是开发具有增强的抗菌活性、增强的氟化物释放和再充电以及其他能力的新型单体，并将它们与氟化物释放填料和生物活性填料联合收割机结合，以克服与当前复合材料、粘合剂和密封剂相关的限制其防龋功效和修复寿命的多种问题。该项目有四个具体目标：（1）配制和优化新型抗菌氟化物释放牙科复合材料，（2）配制和优化新型水解稳定的氟化物释放牙科粘合剂，（3）配制和表征新型抗菌生物活性密封剂，其释放钙、磷酸盐和氟化物，（4）通过人工龋模型测试新型防龋牙科材料体系的整体抑龋效果。假设是：（1）含有新型氟化物交换单体的牙科材料将具有增强的氟化物释放和再充电能力，同时保持足够或改善的物理和机械性能。(2)抗微生物活性与增强的再矿化能力的组合将协同导致修复材料的显著更高的龋齿抑制功效。(3)抗菌氟化物释放复合物、粘合剂和生物活性密封剂的组合使用将进一步减少龋齿。本项目旨在开发一系列抗菌、释氟、生物活性牙科材料。预计这些材料的防龋功效比现有的树脂基牙科材料更强。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，特别是对于广大的高龋齿风险患者（患有口干症或口干的医疗损害者，儿童，老年人，精神或身体有障碍的人）。

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).