Host and bacterial enzyme-mediated approaches to produce durable direct and indirect restorations

宿主和细菌酶介导的方法产生持久的直接和间接修复

• 批准号: 9765078
• 负责人: Carmem S. Pfeifer
• 金额: $ 49.5万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-03-01 至 2020-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9765078
• 关键词: Address; Adhesives; Affect; Age; Amides; Ammonium; Anti-Bacterial Agents; Antibiotics; Bacteria; Binding Sites; Biocompatible Materials; Bioreactors; Capsid Proteins; Catalytic Domain; Cell Membrane Proteins; Chelating Agents; Chlorhexidine; Clinical; Cohort Studies; Collagen; Composite Resins; Dental; Dental Materials; Dental caries; Dental crowns; Dentin; Disease; Ecology; Endocarditis; Environment; Enzymes; Esthetics; Fracture; Gelatinase A; General Population; Glucans; Glucose; Gram-Positive Bacteria; Healthcare; Hybrids; Hydrolysis; Immobilization; Infection; Kinetics; Longevity; Materials Testing; Matrix Metalloproteinases; Mechanics; Mediating; Metabolic; Methacrylates; Microbial Biofilms; Modeling; Mouthwash; Nature; Nitro Compounds; Oral; Oral Pathology; Oral cavity; Organism; Pathogenicity; Patients; Penetration; Periodontal Diseases; Physiological; Plant Resins; Polymers; Polysaccharides; Population; Prevention; Procedures; Production; Property; Public Health; Reaction; Recurrence; Resistance; Retreatment; Risk; Saliva; Specificity; Streptococcus gordonii; Streptococcus mutans; Structure; Surface; System; Technology; Testing; Time; Tissues; Tooth structure; Toothpaste; Translations; Triclosan; Underserved Population; Water; aging population; analog; antimicrobial; antimicrobial drug; bactericide; base; cancer therapy; collagenase; commensal bacteria; composite restoration; design; dysbiosis; esterase; extracellular; glycosyltransferase; improved; inhibitor/antagonist; mechanical load; mechanical properties; methacrylamide; microbial; monomer; novel; oral bacteria; polymerization; preservation; prevent; restoration; restorative composite; restorative material; small molecule

Summary Dental caries continues to be a public health issue, especially more evident in underserved populations throughout the U.S. Unfortunately, especially with an ageing population, hundreds of thousands of resin composite restorations are replaced each year due to recurring decay and fracture. According to a number of cohort studies, the average life-span of this type of restoration is 10 years or less, depending on the caries risk level of the patient and on the complexity of the restorative procedure. This proposal represents an effort to develop novel antimicrobial structures, based on a targeted approach specifically against dysbiotic biofilm. Bacterial coalescence will be prevented by using GTF inhibitors, made polymerizable by functionalization with stable methacrylamides. In addition, MMP-inhibiting moieties will be added to a polymerizable monomer, improving the stability of the collagen in the hybrid layer. Ultimately, this will save millions of dollars annually and the unnecessary loss of additional tooth structure that comes with every re-treatment. The proposed approach will improve the longevity of restorations by: 1. Designing monomers containing known GTF-inhibiting moieties, thus making them available non-transiently at the surface of restorations. 2.Utilizing polymerizable functionalities that depart from the water/esterase-labile methacrylates. Methacrylamides are well known for their resistance to degradation by hydrolysis, and the systems proposed here will also be stable to enzymatic attack. 3. Incorporating MMP-inhibiting moieties on the methacrylamide monomer to the used as the adhesive, thus preserving the integrity of the collagen long-term. 4. Testing the materials in a physiologically relevant environment, mimicking the conditions in the mouth in terms of mechanical loading, bacterial challenge and presence of saliva.

概括 龋齿仍然是一个公共卫生问题，尤其是在服务不足的情况下更为明显 不幸的是，美国各地的人口，尤其是人口老龄化，数百人 每年由于反复衰减和 断裂。根据许多队列研究，这种类型的平均寿命 恢复是10年或更短的时间，具体取决于患者的龋齿风险水平和 修复程序的复杂性。该提议代表着发展小说的努力 抗菌结构，基于针对不良生物生物膜的靶向方法。 通过使用GTF抑制剂，可以预防细菌结合，可通过 稳定的甲基丙烯酰胺的功能化。此外，还将添加抑制MMP的部分 到可聚合的单体，改善了杂化层中胶原蛋白的稳定性。 最终，这将每年节省数百万美元，并不必要地损失额外的牙齿 每次重新治疗都带来的结构。拟议的方法将改善寿命 恢复作者：1。设计包含已知GTF抑制部分的单体，因此 使它们在修复体的表面上非频繁。 2.利用聚合物 脱离水/酯酶 - 酸酯甲基丙烯酸酯的功能。甲基丙烯酰胺是 以水解对降解的抵抗而闻名，此处提出的系统将 也可以稳定酶促攻击。 3。在 甲基丙烯酰胺单体与用作粘合剂，从而保留了 胶原蛋白长期。 4。在生理相关环境中测试材料，模仿 在机械载荷，细菌挑战和存在方面，口中的条件 唾液。