Peptide Enabled Tunable Restorative Interface

项目总结 在美国儿童中，龋病是最常见的慢性病，也是最常见的未治愈疾病之一 医疗保健需求。服务不足和有特殊需要的患者群体的龋齿负担更高，即， 未经治疗的龋齿是发育障碍儿童的一个主要健康问题。治疗龋齿 传统上，病变需要使用高速钻头和外科手术去除病变的牙齿结构 伴随着为幼儿或有特殊需要的人提供广泛的牙科恢复性治疗，可以 需要全身麻醉或深度镇静，需要将儿童转介给牙科专家的步骤，以及 高得离谱的住院费用。与未经治疗的儿童早期龋齿(ECC)相比，未经治疗的早期龋齿扩散更快 对成年人的牙齿，并发展短期和长期的重大健康问题。唯一非侵入性的，有效的 在美国，预防龋齿的治疗方法是氟化二胺(SDF)。SDF获得了FDA的批准 2014年，并获得了治疗儿童龋齿的突破性疗法称号。然而，永久的 SDF治疗的龋损的黑色染色限制了这种治疗的可接受性和采用。此外， SDF现场形成的新界面引起了人们对复合材料粘结减少的担忧 通常用来遮盖污渍。最近对SDF处理的研究表明，银的形成 复合体填充空洞并穿透牙本质小管。这项建议解决了临床上的迫切需要 通过开发银靶向非侵入性治疗儿童和有特殊需要的人群的龋病 仿生界面，与SDF协同工作，在减少龋齿的同时阻止龋齿和牙齿的再矿化 银氧化，导致黑色染色。我们假设以银为靶标的可聚合多肽 化合物和作为再矿化剂将减缓银氧化，促进牙齿再矿化， 增强SDF-牙界面的性能，阻止龋病的发生。我们实验室的最新发现支持这一假设 并为满足这一紧迫需求提供重大承诺。首先，我们设计了包含以下成分的双功能多肽 银结合结构域(AgBP)，自组装并在SDF治疗的龋病处介导再矿化 损伤。其次，我们开发了一种可聚合的AgBP，通过将其与甲基丙烯酸连接起来用作多肽- 牙本质粘合剂中的单体。第三，我们证明了AgBP-单体在SDF上的自组装 经处理的界面显著减少了银氧化过程。在我们进展的基础上，该提案 探索：目的1)通过优先与银相互作用来改善界面性质的工程多肽 目的：2)聚合肽-聚合物树脂，以减少 AG氧化过程，并提供与SDF的持久结合；目标3)与SDF和多肽-聚合物共处理 与单独使用SDF处理相比，树脂可提供更耐用、更坚固的界面粘结。这个 拟议中的应用可能会通过阻止龋齿、重新矿化 减少因单独使用SDF而导致的黑染的副作用。

PROJECT SUMMARY Among U.S. children, caries is the single most common chronic disease and one of the most common unmet health care needs. Underserved and special needs patient populations have a higher caries burden, i.e., untreated dental caries is a major health problem for children with developmental disabilities. Treating carious lesions conventionally requires surgical removal of diseased tooth structure using high-speed drills and the accompanying extensive dental restorative treatment for young children or persons with special needs may require general anesthesia or deep sedation, steps which require referring the child to a dental specialist and concordant high hospitalization costs. Untreated early childhood caries (ECC) spreads more rapidly compared to adult teeth and develops both short- and long-term significant health issues. The only noninvasive, efficacious treatment option in the U.S. for arresting caries is silver diamine fluoride (SDF). SDF was approved by the FDA in 2014 and granted a breakthrough therapy designation for treating caries in children. However, permanent black staining of SDF-treated caries lesions limited the acceptability and adoption of this treatment. Besides, the new interface formed at the SDF site raised concerns regarding reduced bonding of composite materials commonly used to mask the staining. Recent studies on SDF treatment indicated the formation of silver complexes filling the cavities and penetrating dentin tubules. This proposal addresses the urgent clinical need for noninvasive treatment for caries in children and persons with special needs by developing a silver targeting biomimetic interface that works synergistically with SDF to arrest caries and remineralize the tooth while reducing silver oxidation which leads to black staining. We hypothesize that polymerizable peptides targeting silver compounds and acting as remineralization agents will slow silver oxidation, promote tooth remineralization, enhance properties of SDF-tooth interface and arrest caries. Recent findings from our lab support this hypothesis and offer significant promise for meeting this urgent need. First, we engineered bifunctional peptides containing a silver-binding domain (AgBP) that self assembles and mediates remineralization at the SDF treated carious lesion. Second, we developed a polymerizable AgBP by tethering it to methacrylic acid for use as a peptide- monomer in dentin adhesive. Third, we demonstrated that self-assembly of the AgBP-monomer at the SDF treated interface significantly reduces the silver oxidation process. Building on our progress, the proposal exploits: Aim 1) engineered peptides to improve interface properties by preferentially interacting with silver complexes and remineralizing the SDF-treated lesions; Aim 2) polymerized peptide-polymer resins to reduce the Ag oxidation process and provide durable bonding with SDF; Aim 3) co-treatment with SDF and peptide-polymer resins to provide more-durable, mechanically robust interfacial bonds compared to SDF treatment alone. The proposed application has the potential to directly impact oral health disparities by arresting caries, remineralizing the tooth, and reducing the stigmatizing side effect of black staining associated with SDF treatment alone.