High Performance Antimicrobial Fluoride Releasing Dental Materials

高性能抗菌释氟牙科材料

• 批准号: 9471812
• 负责人: XIAOMING XU
• 金额: $ 42.91万
• 依托单位: LSU HEALTH SCIENCES CENTER
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-04-13 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9471812
• 关键词: Affect; Ammonium; Animals; Anti-Bacterial Agents; Antimicrobial Effect; Cariogenic Diet; Ceramics; Chelating Agents; Clinical Trials; Collaborations; Dental; Dental Bonding; Dental Enamel; Dental Materials; Dental caries; Dentin; Dentin-Bonding Agents; Development; Esthetics; Failure; Film; Fluorides; Fracture; Funding; Gallium; General Population; Generations; Glass; Goals; Growth; Healthcare; In Vitro; Ions; Lactobacillus casei; Length; Lesion; Life; Matrix Metalloproteinases; Methacrylates; Microbial Biofilms; Microbiology; Modeling; Mouth Diseases; Nanotubes; Odontogenesis; Oral health; Oxides; Patient risk; Pennsylvania; Performance; Phase; Plant Resins; Quality of life; Rattus; Recurrence; Rodent; Salts; Series; Services; Silicon Dioxide; Silver; Streptococcus mutans; System; Testing; Time; Tooth structure; Universities; Zirconium; anticaries; antimicrobial; antimicrobial drug; base; biomaterial compatibility; clinical candidate; composite restoration; controlled release; cytotoxicity; efficacy testing; halloysite; high risk; improved; in vitro Model; in vivo; mechanical properties; monomer; nanofiber; nanoparticle; novel; oral biofilm; particle; physical property; restoration; restorative material; yttria; zirconium oxide

Project Summary/Abstract The goal of this R01 proposal is to develop high-performance antimicrobial fluoride-releasing dental materials (composite and dentin bonding agent). Secondary (recurrent) caries and bulk fracture are the leading causes of failure of composite restorations and thus limit their service life. Much effort has been directed towards the development of dental materials that can inhibit bacterial biofilms and reduce secondary caries. However, the composites containing soluble anticariogenic agents or (nano)particles of ACP or CaF2 usually have poor mechanical properties. The antibacterial materials containing silver nanoparticles usually have unacceptable dark shade. In our previous funding period (R01DE019203), we synthesized several novel F-releasing methacrylate monomers and antibacterial monomer containing long-chain quaternary ammonium salts (QAS). We developed a series of novel antibacterial fluoride-releasing materials (dental composites, bonding agents and sealants). They have shown enhanced fluoride-releasing and recharge capabilities, promising antibacterial effect, and good mechanical properties or bonding strength. However, the amount of antibacterial monomers that could be incorporated in these materials was rather limited (~3%) thus limiting its antibacterial activity. To overcome this limitation, we synthesized several new antibacterial monomers bearing different chain lengths and we discovered that a small amount (1-1.5%) of a short-chain QAS monomer, when used together with other long-chain QAS, could significantly increase antibacterial effect. Additionally, it could improve the mechanical properties of the composite. We have also developed new translucent silica-zirconia- yttria ceramic nanofibers and  white gallium (hydrous)oxide-loaded mesoporous silica nanopartilces (Ga@MSN). Gallium (III) ions and compounds are safe antimicrobial agents but they have not been used in resin-based dental materials. We hypothesize: (1) the synergistic combination of antibacterial monomers containing varying chain lengths (enhanced contact-killing) and gallium (hydrous)oxide nanoparticles (pH- responsive controlled release of Ga ions) can significantly increase the antibacterial and biofilm-inhibitory effects; and (2) the new antimicrobial fluoride-releasing dental material system will possess significant anti- caries efficacy, excellent mechanical properties, desirable aesthetics, and a long service life. In this proposed project, we will further develop novel high-performance antimicrobial fluoride-releasing dental materials with three aims: In Aim 1, we will formulate and optimize a series of high-performance antimicrobial fluoride- releasing dental materials (composite and  dentin bonding agent) by blending the fluoride-releasing monomer and new antibacterial monomers, Ga@MSN, translucent ceramic nanofibers and halloysite nanotubes, fluoride-releasing glass particles, and photoinitiators. We will test and optimize the physical and mechanical properties, bonding strength, cytotoxicity and biocompatibility.. In Aim 2, we will test the hypothesis that the novel antimicrobial F-releasing dental materials will significantly reduce cariogenic bacterial biofilms and secondary caries using an in vitro biofilm-artificial caries model on extracted teeth. In Aim 3, in collaboration with Dr. Hyun Koo at University of Pennsylvania, we will test the hypothesis that the novel antimicrobial F- releasing dental materials will significantly reduce secondary caries using in vivo animal (rat) caries models. Our long-term goal is to develop a new generation of dental materials that have a high efficacy to inhibit oral biofilm formation as well as excellent mechanical properties. The novel dental materials developed in this project will have significantly longer service life and will be excellent candidates for clinical trials of high caries-risk patients.

项目摘要/摘要 本R01提案的目标是开发高效抗微生物氟化物释放剂 牙科材料(复合体和牙本质粘结剂)。继发性(复发性)龋病和大块骨折 这是导致复合修复体失败的主要原因，从而限制了它们的使用寿命。我们已经付出了很多努力 旨在开发能够抑制细菌生物被膜并减少继发感染的牙科材料 龋齿。然而，含有可溶性抗龋剂或(纳米)ACP或CaF2颗粒的复合材料 通常具有较差的机械性能。含银纳米粒子的抗菌材料通常 有不可接受的深色。在我们之前的资助期间(R01DE019203)，我们合成了几个新的 含长链季铵盐的甲基丙烯酸酯释氟单体和抗菌单体 盐(QAS)。我们开发了一系列新型抗菌释氟材料(牙科复合材料， 粘结剂和密封剂)。它们表现出了增强的氟化物释放和充电能力， 良好的抗菌效果，良好的机械性能或粘接强度。然而，这一数量 可掺入这些材料中的抗菌单体相当有限(~3%)，因此限制了其 抗菌活性。为了克服这一局限性，我们合成了几种新的抗菌单体 不同的链长，我们发现少量(1-1.5%)的短链QAS单体，当 与其他长链QAS联合使用，可显著提高抗菌效果。此外，它还可能 提高了复合材料的力学性能。我们还开发了新的半透明二氧化硅-氧化锆- 氧化钇陶瓷纳米纤维和载白(水)氧化镓介孔二氧化硅纳米粒子 (GA@MSN)。镓(III)离子和化合物是安全的抗菌剂，但它们尚未用于 树脂基牙科材料。我们假设：(1)抗菌单体的协同组合 含有不同链长(增强接触杀伤力)和氧化镓(水合)纳米颗粒(pH- 响应性控制释放镓离子)能显著提高抗菌和生物被膜抑制作用 以及(2)新型抗微生物氟化物释放牙科材料系统将具有显著的抗 龋齿功效、优异的机械性能、理想的美观和较长的使用寿命。在本建议中 项目，我们将进一步开发新型高效抗微生物氟化物释放牙科材料 三个目标：目标一，我们将配方和优化一系列高性能抗菌剂氟化物-- 混合释氟单体释放牙科材料(复合牙本质粘结剂和牙本质粘结剂) 以及新型抗菌单体Ga@MSN，半透明陶瓷纳米纤维和埃洛石纳米管， 氟化物释放玻璃颗粒和光引发剂。我们将对物理和机械进行测试和优化 性能、结合强度、细胞毒性和生物相容性。在目标2中，我们将测试假设 新型抗菌氟释放牙科材料将显著减少致龋菌生物膜和 体外生物膜-人工龋齿模型在拔除牙齿上的继发性龋病研究。在AIM 3中，在协作中 与宾夕法尼亚大学的古贤博士一起，我们将检验这样一个假设，即新型抗菌剂F- 在活体动物(大鼠)龋齿模型中，释放牙科材料将显著减少继发性龋齿。 我们的长期目标是开发出高效抑制口腔的新一代牙科材料 生物膜的形成以及优异的机械性能。在这方面开发的新型牙科材料 该项目将具有更长的使用寿命，并将是临床试验的优秀候选者 有高龋齿风险的患者。