Peptide Enabled Tunable Restorative Interface

项目摘要 在美国儿童中，龋齿是最常见的慢性疾病，也是最常见的未得到满足的疾病之一。 保健需要。服务不足和有特殊需要的患者群体有更高的龋齿负担，即， 未经治疗的龋齿是发育障碍儿童的主要健康问题。治疗龋齿 病变通常需要使用高速钻头手术去除患病的牙齿结构， 对幼儿或有特殊需要的人进行广泛的牙齿修复治疗， 需要全身麻醉或深度镇静，这些步骤需要将儿童转诊给牙科专家， 住院费用高。未经治疗的幼儿龋齿（ECC）传播更快， 成年人的牙齿，并发展短期和长期的重大健康问题。唯一一种非侵入性的，有效的 在美国用于阻止龋齿的治疗选择是银二胺氟化物（SDF）。SDF已获FDA批准 并获得了治疗儿童龋齿的突破性疗法称号。然而，永久 SDF处理的龋齿损伤的黑色染色限制了这种治疗的可接受性和采用。而且 在自卫队基地形成的新界面引起了人们对复合材料粘接性能下降的关注 通常用于掩盖染色。最近对SDF处理的研究表明形成了银 复合物填充空腔并穿透牙本质小管。该提案解决了迫切的临床需求 通过开发一种银靶向， 仿生界面，与SDF协同工作，以阻止龋齿和牙齿矿化，同时减少 银氧化导致黑色染色。我们假设靶向银的可聚合肽 化合物和作为矿化剂将减缓银氧化，促进牙齿矿化， 增强SDF-牙齿界面的性能，阻止龋齿。我们实验室最近的发现支持了这一假设 并为满足这一迫切需求提供了重要的承诺。首先，我们设计了双功能肽， 一个银结合结构域（AgBP），在SDF处理的龋损处自组装并介导再矿化 损伤。第二，我们开发了一种可聚合的AgBP，将其与甲基丙烯酸连接，用作肽- 牙本质粘结剂中的单体。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。根据我们的进展， 开发：目的1）通过优先与银相互作用来改善界面性质的工程化肽 目的2）聚合肽-聚合物树脂，以减少 银氧化过程，并提供与SDF的持久结合;目的3）与SDF和肽-聚合物的共处理 与单独的SDF处理相比，的 所提出的应用有可能通过阻止龋齿、促进口腔健康、 牙齿，并减少与单独SDF治疗相关的黑染色的污名化副作用。

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.