Novel Antibacterial Fluoride-releasing Dental Materials

描述(申请人提供)：我们建议研究和开发抗菌和/或氟化物释放的新型牙科材料，并协同作用形成高效的抑龋修复体系统。这些材料预计将对人口中最脆弱、高龋齿风险部分的口腔健康产生巨大影响：患有口干症或口干(由于Sjvgren综合征、糖尿病、头颈部照射和药物)的医学受损群体、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)龋病仍然是其替代的主要原因。因此，许多工作都集中在开发能够释放氟化物等防龋剂的复合材料上。然而，目前的牙科复合材料在氟化物释放和氟化物补充能力方面都存在缺陷，而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结剂，以减少边缘渗漏和限制继发性龋齿。然而，非氟释放粘结剂和低氟释放粘结剂本质上都是氟向龋齿易发地区运输的障碍。另一个问题是，大多数自酸蚀牙科粘结剂容易发生水解性降解，最终导致渗漏、继发性龋齿和红细胞寿命缩短。在主要的龋齿预防方面，密封剂，包括释放氟化物的密封剂，已经显示出防腐效果，但牙科专业采用密封剂的速度一直很慢，部分原因是担心龋齿会在封闭的凹坑和裂隙下继续恶化。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补给等能力的新型单体，并将其与氟化物释放填充剂和生物活性填充剂结合起来，以克服与当前的复合材料、粘结剂和密封剂相关的多重问题，这些问题限制了它们的防龋性和修复寿命。本项目有四个具体的目标：(1)研制和优化新型抗菌释氟牙科复合材料；(2)研制和优化新型水解性稳定释氟型牙科粘结剂；(3)研制并表征新型钙、磷、氟抗菌生物活性封闭剂；(4)通过人工龋病模型检测新型防腐牙科材料体系的防龋性。这些假设是：(1)含有新型氟离子交换单体的牙科材料在保持足够或改善的物理和机械性能的同时，将具有更强的氟化物释放和补充能力。(2)抗菌活性与再矿化能力的结合将协同作用使修复材料的抑龋率显著提高。(3)抗菌释氟复合材料、粘结剂和生物活性封闭剂的联合使用将进一步减少龋病。该项目旨在开发一系列具有抗菌、氟化物释放和生物活性的牙科材料。这些材料有望比现有的基于树脂的牙科材料具有更强的防龋性。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，特别是对广大高龋齿患者(患有口干症或口干症的医学受损患者、儿童、老年人、智力或身体残疾的人)。

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).