Peptide-Polymer Engineering Dentin/Adhesive Interfacial Bond Integrity

项目摘要 反复复合修复替换的循环是一个有害的问题--每次替换都有风险 牙髓损伤，牙齿软弱加剧，最终导致牙齿脱落。这个问题是普遍存在的--近70%的人 复合修复体是一种替代物，失败的主要原因是复发性边缘腐烂。不像 银汞合金，复合材料缺乏固有的能力来封闭材料/牙齿界面的差异。这个 将复合材料粘接到牙齿上的粘结剂旨在密封界面，但粘接剂密封到牙本质上 是易碎的--它很容易被酸、酶和其他口腔液体损坏。细菌和细菌副产物 渗入由此产生的边缘缝隙，使牙齿脱矿和分解，并进一步侵蚀粘合剂， 导致更大更深的差距，为细菌繁殖创造了理想的环境。生物降解性- 产物聚集在牙本质/粘附剂界面上，增加了致龋菌的毒力， 引发了一个正反馈循环，使退化升级。目前迫切需要解决这一问题 复合/牙齿界面的脆弱性通过多因素方法：i)重新矿化受损的牙本质； Ii)抑制细菌侵袭；以及iii)提供耐用的聚合物。我们实验室的最新发现提供了巨大的希望 以满足这一需求。首先，我们合成了新型的自增强聚合物--自增强聚合物 机理提供了在中性和酸性条件下对聚合物网络的持久的、内在的强化 条件。我们已经设计了抗菌肽和再矿化肽，并将它们与自身 增强型粘合单体。在我们进展的基础上，我们建议同时使用工程化多肽和 将抗菌剂与新型聚合物捆绑在一起，提供一种将用作耐久粘合剂的“生物杂化”粘合剂 防止反复腐烂的屏障。我们的三重策略利用：(I)聚合物系留工程多肽和 同时提供抗菌活性、延缓生物膜形成和再矿化的抗菌剂 牙本质；(Ii)抗水解性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.