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

摘要 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，并减少不必要的额外牙齿损失 每一次再治疗都会有这样的结构。建议的方法将提高寿命。 通过：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。甲基丙烯酰胺是 众所周知，它们能抵抗水解物的降解，而这里提出的系统将 对酶的攻击也稳定。3.将抑制基质金属蛋白酶的部分结合在 将甲基丙烯酰胺单体用作粘合剂，从而保持了胶粘剂的完整性 胶原蛋白长期有效。4.在生理相关的环境中测试材料，模拟 口腔中的情况，如机械负荷、细菌挑战和是否存在 唾液。

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.