High Performance Antimicrobial Fluoride Releasing Dental Materials

高性能抗菌释氟牙科材料

• 批准号: 9904114
• 负责人: XIAOMING XU
• 金额: $ 56.42万
• 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/9904114
• 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; Patients; Pennsylvania; Performance; Phase; Plant Resins; Quality of life; Rattus; Recurrence; Risk; 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; dental biofilm; efficacy testing; halloysite; high risk; improved; in vitro Model; in vivo; mechanical properties; monomer; nanofiber; nanoparticle; novel; oral biofilm; particle; physical property; polymicrobial biofilm; 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 该R01提案的目的是开发高性能抗菌氟化物释放 牙科材料（复合和牙本质键合剂）。次要（反复）龋齿和散装骨折是 复合修复体失败的主要原因，从而限制其使用寿命。努力很多 致力于开发可以抑制细菌生物膜并减少继发性的牙科材料 携带。然而，含有固体抗核生成剂或ACP或CAF2的（纳米）颗粒的复合材料 通常的机械性能较差。通常含有银纳米颗粒的抗菌材料 有不可接受的黑暗阴影。在我们以前的资金期（R01DE019203）中，我们合成了几种小说 F-释放的甲氧铁单体和含有长链季铵的抗菌单体 盐（QAS）。我们开发了一系列新型抗菌氟化物释放材料（牙科复合材料，， 粘合剂和密封剂）。他们显示出增强的氟化物释放和充电功能， 有希望的抗菌作用以及良好的机械性能或粘结强度。但是，数量 可以在这些材料中掺入的抗菌单体相当有限（〜3％），从而限制了其 抗菌活性。为了克服这一限制，我们合成了几个新的抗菌单体 不同的链长，我们发现短链QAS单体的少量（1-1.5％） 与其他长链QA一起使用，可以显着增加抗菌作用。另外，它可以 改善复合材料的机械性能。我们还开发了新的半透明二氧化硅-jirconia- Yttria陶瓷纳米纤维和白色镀金（含水）氧化物的介孔二氧化硅纳米肌 （ga@msn）。甘露（III）离子和化合物是安全的抗菌剂，但尚未使用 基于树脂的牙科材料。我们假设：（1）抗菌单体的协同组合 包含不同的链长（增强的接触式杀伤）和甘油（含水）氧化物纳米颗粒（pH-） GA离子的响应式控制释放）可以显着增加抗菌和生物膜抑制作用 效果； （2）新的抗菌氟化物释放牙科材料系统将具有明显的抗 龋齿有效性，出色的机械性能，理想的美学以及长期使用寿命。在此提案中 项目，我们将进一步开发新型的高性能抗菌抗菌氟化物的牙科材料 三个目标：在AIM 1中，我们将制定和优化一系列高性能抗菌氟化物 - 通过混合释放氟化物释放单体的释放牙科材料（复合材料和牙本质键合剂） 以及新的抗菌单体，GA@MSN，半透明的陶瓷纳米纤维和万圣节纳米管， 释放氟化物的玻璃颗粒和光起剂。我们将测试和优化物理和机械 性质，粘结强度，细胞毒性和生物相容性。在AIM 2中，我们将检验以下假设。 新型的抗菌抗菌F-释放牙科材料将显着降低致癌细菌的生物膜和 二级汽车使用拔出牙齿的体外生物膜人工汽车模型。在AIM 3中，合作 在宾夕法尼亚大学的Hyun Koo博士中，我们将检验以下假设。 释放牙科材料将使用体内动物（大鼠）汽车模型大大减少次要汽车。 我们的长期目标是开发新一代的牙科材料，这些牙科材料具有很高的效率来抑制口腔 生物膜形成以及优秀的机械性能。在此开发的新型牙科材料 项目的使用寿命将大大延长，并且将成为临床试验的出色候选者 高性危险患者。