Peptide-Polymer Engineering Dentin/Adhesive Interfacial Bond Integrity

项目摘要 重复的复合修复替换循环是一个有害的问题--每次替换都有风险 牙髓损伤，牙齿虚弱，最终，牙齿脱落。这个问题是普遍存在的， 复合材料涂层是替换涂层，失效的主要原因是经常性的边缘腐蚀。不像 汞合金复合材料缺乏密封材料/牙齿界面处的差异的固有能力。的 将复合材料粘合到牙齿上的粘合剂旨在密封界面，但粘合剂会密封牙本质 是脆弱的-它很容易被酸、酶和其他口腔液体破坏。细菌和细菌副产物 渗透所产生的边缘间隙，使牙齿去矿物质化和分解，并进一步侵蚀粘合剂， 导致更宽和更深的缝隙，为细菌繁殖创造了理想的环境。生物降解- 产物在牙本质/粘合剂界面处积聚并增加致龋细菌的毒力， 引发了一个正反馈循环，加剧了退化。迫切需要解决这一问题 复合材料/牙齿界面的脆弱性通过多因素的方法，i）破坏牙本质; ii）抑制细菌侵袭;和iii）提供耐久聚合物。我们实验室最近的发现提供了重大的希望 来满足这一需求。首先，我们合成了一种新型的自增强聚合物-自增强聚合物 该机制提供了一个持久的，内在的增强聚合物网络在中性和酸性 条件我们已经设计了抗菌肽和抗菌肽，并将它们连接到自我- 增强粘合剂单体。基于我们的进展，我们建议使用工程肽和 将抗菌剂与新型聚合物结合，以提供一种“生物混合”粘合剂， 对复发性衰变的屏障。我们的三重策略利用：（i）聚合物栓系的工程化肽和 抗菌剂，同时提供抗菌活性、延迟生物膜形成和抗菌化， 牙本质;（ii）抵抗水解介导的降解的自增强聚合物;和（iii）迭代反馈 在合成、表征和建模之间，以预测在相关体内条件下的性能。

Project Summary The cycle of repeated composite-restoration replacements is a pernicious problem—each replacement risks pulpal injury, increased tooth weakness, and eventually, tooth loss. The problem is pervasive—nearly 70% of all composite restorations are replacements and the leading cause of failure is recurrent marginal decay. Unlike amalgam, composite lacks the inherent capability to seal discrepancies at the material/tooth interface. The adhesive that bonds the composite to the tooth is intended to seal the interface, but the adhesive seal to dentin is fragile—it is readily damaged by acids, enzymes, and other oral fluids. Bacteria and bacterial by-products infiltrate the resulting marginal gaps, demineralize and decompose the tooth, and further erode the adhesive, leading to wider and deeper gaps that create an ideal environment for bacteria to proliferate. Biodegradation by- products accumulate at the dentin/adhesive interface and increase the virulence of cariogenic bacteria, provoking a positive feedback loop that escalates the degradation. There is an urgent need to address this composite/tooth-interface vulnerability through multi-factorial approaches that: i) remineralize damaged dentin; ii) inhibit bacterial attack; and iii) provide durable polymers. Recent findings from our lab offer significant promise for meeting this need. First, we have synthesized novel self-strengthening polymers—the self-strengthening mechanism provides a persistent, intrinsic reinforcement of the polymer network in both neutral and acidic conditions. We have engineered antimicrobial and remineralizing peptides and tethered them to self- strengthening-adhesive monomers. Building on our progress, we propose to use both engineered peptides and antibacterial agents tethered to novel polymers to provide a “bio-hybrid” adhesive that will serve as a durable barrier to recurrent decay. Our threefold strategy exploits: (i) polymer-tethered engineered peptides and antibacterial agents to simultaneously provide antibacterial activity, delay biofilm formation, and remineralize dentin; (ii) self-strengthening polymers that resist hydrolysis-mediated degradation; and (iii) iterative feedback between synthesis, characterization, and modeling to forecast performance under relevant in vivo conditions.