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: 10228724
• 负责人: Carmem S. Pfeifer
• 金额: $ 97.43万
• 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/10228724
• 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/antagonist; 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更为明显 不幸的是，尤其是随着人口老龄化，美国各地的人口 由于反复腐烂和损坏，每年有数以千计的树脂复合材料修复体被更换 断裂。根据多项队列研究，此类人群的平均寿命 修复期为 10 年或更短，具体取决于患者的龋齿风险水平以及 恢复过程的复杂性。该提案代表了开发新颖的努力 抗菌结构，基于专门针对菌群失调生物膜的针对性方法。 使用 GTF 抑制剂可防止细菌聚结，GTF 抑制剂可聚合 用稳定的甲基丙烯酰胺进行官能化。此外，还将添加 MMP 抑制部分 到可聚合单体，提高混合层中胶原蛋白的稳定性。 最终，这将每年节省数百万美元，并避免不必要的额外损失 每次重新治疗时都会出现牙齿结构。所提出的方法将改善 通过以下方式延长修复体的寿命： 1. 设计含有已知 GTF 抑制部分的单体，从而 使它们在修复体表面非暂时可用。 2.利用聚合性 与水/酯酶不稳定的甲基丙烯酸酯不同的功能。甲基丙烯酰胺效果很好 以其抗水解降解而闻名，这里提出的系统也将是 对酶攻击稳定。 3. 在甲基丙烯酰胺单体上掺入 MMP 抑制部分 用作粘合剂，从而长期保持胶原蛋白的完整性。 4. 测试 生理相关环境中的材料，模仿口腔中的条件 机械负荷、细菌挑战和唾液的存在。