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的疾病之一 医疗保健需求。服务不足和特殊需求患者人群的龋齿负担更高，即 未经治疗的龋齿是发育障碍儿童的主要健康问题。治疗狂热 病变通常需要使用高速钻头手术去除患病的牙齿结构， 伴随着针对有特殊需要的幼儿或患者的大量牙科修复治疗可能 需要全身麻醉或深层镇静，需要将孩子转介给牙科专家， 一致的高住院费用。未经治疗的幼儿龋齿（ECC）的传播更快地比较 成人牙齿并出现短期和长期重大健康问题。唯一的无创，有效的 美国逮捕龋齿的治疗方案是二氧化菊酯（SDF）。 SDF已由FDA批准 2014年，并授予了用于治疗儿童龋齿的突破疗法。但是，永久 SDF处理的龋齿病变的黑色染色限制了这种治疗方法的可接受性和采用。此外， 在SDF站点形成的新界面引起了人们对复合材料粘结减少的担忧 通常用于掩盖染色。关于SDF处理的最新研究表明银的形成 配合物充满腔和穿透牙本质小管。该建议解决了紧急临床需求 通过开发银色靶向的儿童和有特殊需求的人的龋齿无创治疗 仿生界面与SDF协同作用以阻止龋齿并减少牙齿。 银氧化会导致黑色染色。我们假设靶向银的可聚合肽 化合物和充当回想剂的化合物将减慢银氧化，促进牙齿回忆化， 增强SDF牙齿界面和龋齿的特性。我们实验室的最新发现支持这一假设 并为满足这种迫切需求提供了巨大的希望。首先，我们设计了包含的双功能肽 自我组装并介导SDF治疗的Carious的银结合域（AGBP） 病变。其次，我们通过将其链接到甲基丙烯酸以用作肽 - 牙本质粘合剂中的单体。第三，我们证明了SDF的AGBP学位者的自组装 处理过的界面可显着减少银氧化过程。在我们的进步的基础上，提案 利用：AIM 1）通过优先与银相互作用的工程肽来改善界面性能 复合物并将SDF治疗的病变进行复合物；目标2）聚合聚合物聚合物树脂以减少 Ag氧化过程，并与SDF提供持久的键合；目标3）与SDF和肽聚合物共同治疗 与仅SDF治疗相比，树脂提供更可耐用，机械稳健的界面键。这 拟议的申请有可能通过逮捕龋齿，回忆起来直接影响口腔健康差异 牙齿，并减少与仅与SDF治疗相关的黑色染色的污名化副作用。