Peptide Enabled Tunable Restorative Interface

肽启用的可调恢复接口

• 批准号: 10892709
• 负责人: Malcolm L. Snead
• 金额: $ 46.7万
• 依托单位: UNIVERSITY OF KANSAS LAWRENCE
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-07 至 2024-09-06
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10892709
• 关键词: Address; Adhesives; Adoption; Adult; Affect; Behavioral; Binding; Biomimetics; Child; Childhood; Chronic Disease; Clinical; Complex; Data Analyses; Defect; Dental; Dental Enamel; Dental caries; Dentin; Development; Developmental Disabilities; Diamines; Emotional; Engineering; Excision; FDA approved; Feedback; Fluorides; General Anesthesia; Grant; Health; Health Services Accessibility; Healthcare; Hospital Costs; Incisor; Ions; Learning; Lesion; Ligands; Link; Machine Learning; Masks; Mastication; Mechanics; Mediating; Mediator; Modeling; Molecular; Nursery Schools; Oral health; Patients; Penetration; Peptides; Persons; Plant Resins; Polymers; Porosity; Process; Property; Research; Risk; School-Age Population; Sedation procedure; Silver; Silver Compounds; Silver Staining; Site; Specialist; Speed; Stains; Stigmatization; Testing; Tissues; Tooth Diseases; Tooth Remineralization; Tooth structure; Treatment Cost; Work; aged; amelogenin; burden of illness; care costs; compliance behavior; composite restoration; copolymer; cost effective; dental adhesive; design; early childhood; efficacious treatment; global health; health disparity; improved; interfacial; mechanical properties; meetings; methacrylic acid; monomer; multimodality; novel; oxidation; patient population; pediatric patients; physically handicapped; remineralization; restorative material; restorative treatment; self assembly; side effect; synergism; underserved community

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.

项目概要 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 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较高，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进行手术切除患病的牙齿结构， 对幼儿或有特殊需要的人进行广泛的牙齿​​修复治疗可能会 需要全身麻醉或深度镇静，需要将孩子转诊给牙科专家的步骤以及 高昂的住院费用。与未经治疗的儿童早期龋齿 (ECC) 相比，其传播速度更快 到恒牙并产生短期和长期的重大健康问题。唯一无创、有效的 在美国，用于预防龋齿的治疗选择是氟化二胺银 (SDF)。 SDF获得FDA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 SDF 治疗的龋齿病变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发了对复合材料粘合力降低的担忧 通常用于掩盖染色。最近对 SDF 处理的研究表明银的形成 复合物填充空腔并穿透牙本质小管。该提案解决了紧迫的临床需求 通过开发银靶向剂，对儿童和有特殊需要的人的龋齿进行无创治疗 仿生界面与 SDF 协同作用，阻止龋齿并使牙齿再矿化，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 化合物并充当再矿化剂将减缓银氧化，促进牙齿再矿化， 增强 SDF-牙齿界面的性能并阻止龋齿。我们实验室的最新研究结果支持了这一假设 并为满足这一迫切需求提供了重要承诺。首先，我们设计了双功能肽，其中包含 银结合域 (AgBP)，可在 SDF 处理的龋齿上自组装并介导再矿化 病变。其次，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- 牙本质粘合剂中的单体。第三，我们证明了 AgBP 单体在 SDF 上的自组装 经过处理的界面显着减少了银的氧化过程。在我们取得的进展的基础上，该提案 用途：目标 1) 工程化肽通过优先与银相互作用来改善界面特性 复合并重新矿化 SDF 治疗的病变；目标 2) 聚合肽-聚合物树脂以减少 Ag氧化工艺并与SDF提供持久的粘合；目标 3) 与 SDF 和肽聚合物共处理 与单独的 SDF 处理相比，树脂可提供更耐用、机械强度更高的界面粘合。这 拟议的应用有可能通过阻止龋齿、再矿化来直接影响口腔健康差异 牙齿，并减少与单独 SDF 治疗相关的黑色染色的耻辱副作用。