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.

项目总结/摘要 该R01提案的目标是开发高性能的抗微生物氟化物释放 牙科材料（复合材料和牙本质粘合剂）。继发性（复发性）龋齿和大块骨折是 这是复合材料涂层失效的主要原因，从而限制了它们的使用寿命。了很大努力 本发明的目的在于开发能够抑制细菌生物膜并减少二次污染的牙科材料， 龋齿然而，含有可溶性防龋剂或ACP或CaF2的（纳米）颗粒的复合物 通常具有较差的机械性能。含有银纳米颗粒的抗菌材料通常 具有不可接受的深色。在我们之前的资助期（R01DE019203），我们合成了几种新的 含长链季铵盐的释氟甲基丙烯酸酯单体及抗菌单体 盐（QAS）。我们开发了一系列新型抗菌释氟材料（牙科复合材料， 粘合剂和密封剂）。它们显示出增强的氟化物释放和再充电能力， 具有良好的抗菌效果和良好的机械性能或粘结强度。然而， 可以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限制，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 与其它长链QAS配合使用，可显著提高抗菌效果。此外，它可以 提高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负载有白色镓（水合）氧化物的中孔二氧化硅纳米颗粒 (Ga@MSN）。镓（III）离子和化合物是安全的抗微生物剂，但它们还没有用于 树脂基牙科材料我们假设：（1）抗菌单体的协同组合 含有不同的链长（增强的接触杀伤）和氧化镓（水合）纳米颗粒（pH- Ga离子的响应控制释放）可以显著增加抗菌和生物膜抑制 新型抗菌释氟牙科材料体系具有显著的抗 防龋功效、优异的机械性能、理想的美观性和长的使用寿命。在此提出的 项目，我们将进一步开发新型高性能抗菌释氟牙科材料， 三个目标：目标一，研制和优化一系列高性能的氟- 通过共混氟释放单体释放牙科材料（组合物和牙本质粘结剂） 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， 释放氟化物的玻璃颗粒和光引发剂。我们将测试和优化物理和机械 性能、粘合强度、细胞毒性和生物相容性。在目标2中，我们将检验以下假设： 新型抗菌释氟牙科材料将显著减少致龋细菌生物膜， 使用体外生物膜-人工龋模型对拔除的牙齿进行继发性龋研究。在目标3中， 与宾夕法尼亚大学的Hyun Koo博士一起，我们将测试新的抗菌F- 使用体内动物（大鼠）龋齿模型，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新一代的牙科材料，具有高功效，以抑制口腔 生物膜形成以及优异的机械性能。在此期间开发的新型牙科材料 项目将有显着更长的使用寿命，并将成为临床试验的优秀候选人， 高龋齿风险患者。