Novel polymeric materials with improved durability in the oral environment: tailoring responses to host and bacterial enzymes with anti-proteolytic and ecology-based antimicrobial approaches.

在口腔环境中具有更高耐用性的新型聚合物材料：通过抗蛋白水解和基于生态的抗菌方法定制对宿主和细菌酶的反应。

• 批准号: 10443658
• 负责人: Carmem S. Pfeifer
• 金额: $ 94.98万
• 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: 2019-09-01 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10443658
• 关键词: Adhesives; Biocompatible Materials; Clinical; Cohort Studies; Collagen; Composite Resins; Dental; Dental caries; Dental crowns; Ecology; Environment; Enzymes; Esthetics; Fracture; General Population; Healthcare; Hybrids; Hydrolysis; Longevity; Materials Testing; Matrix Metalloproteinases; Methacrylates; Microbial Biofilms; Oral; Oral cavity; Patients; Physiological; Plant Resins; Polymers; Procedures; Public Health; Resistance; Retreatment; Risk; Saliva; Structure; Surface; System; Time; Tissues; Tooth structure; Underserved Population; Water; aging population; antimicrobial; base; collagenase; composite restoration; design; dysbiosis; esterase; improved; inhibitor; mechanical load; methacrylamide; monomer; novel; oral bacteria; preservation; prevent; response; restoration

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.

龋齿仍然是一个公共卫生问题，尤其是在服务不足的地区。 不幸的是，美国各地的人口，特别是老龄化的人口，数以百计 每年数以千计的树脂复合修复体由于反复的腐烂和 骨折。根据多项队列研究，这类人的平均寿命 修复时间为10年或更短，这取决于患者的龋齿风险水平和 恢复性程序的复杂性。这一提议代表了一种开发小说的努力 抗菌结构，基于专门针对非生物膜的有针对性的方法。 将通过使用GTF抑制剂来防止细菌聚集，GTF抑制剂使其可聚合 使用稳定的甲基丙烯酰胺进行官能化。此外，还将添加抑制基质金属蛋白酶的部分 转化为可聚合单体，提高了杂化层中胶原的稳定性。 最终，这将每年节省数百万美元，并带来不必要的额外损失 牙齿结构是每一次再治疗时都会出现的。拟议的方法将改善 修复体的寿命：1.设计含有已知的GTF抑制部分的单体，从而 使它们在修复体表面非瞬时可用。2.利用可聚合材料 与水/酯酶不稳定的甲基丙烯酸酯不同的官能团。甲基丙烯酰胺很好 以其抗水解降解而闻名，这里提出的系统也将是 对酶的攻击稳定。3.在甲基丙烯酰胺单体上引入基质金属蛋白酶抑制基团 将其用作粘合剂，从而长期保持胶原蛋白的完整性。4.测试 在生理相关环境中的材料，模拟口腔中的条件 在机械负荷、细菌挑战和唾液存在方面。