Dentin Biomodification for Optimization of Bioadhesive Dental Restorations

牙本质生物改性优化生物粘附性牙齿修复体

• 批准号: 10294940
• 负责人: Ana Karina B Bedran-Russo
• 金额: $ 48.03万
• 依托单位: MARQUETTE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-15 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10294940
• 关键词: Adhesions; Affect; Anxiety; Binding; Biocompatible Materials; Biomimetics; Chronic Disease; Clinical; Complex; Composite Dental Resin; Composite Resins; Dental; Dental Care; Dental Enamel; Dental Pulp; Dental caries; Dentin; Dentistry; Development; Economics; Exposure to; Extracellular Matrix; Failure; Formulation; Foundations; Goals; Health; Health Care Costs; Homeostasis; Impairment; Incidence; Industrial Waste; Intervention; Left; Life; Ligand Binding; Ligands; Longevity; Mechanics; Mediating; Minerals; Modification; Natural Products; Oral health; Outcome; Pathologic; Patients; Peptide Hydrolases; Performance; Pharmacologic Substance; Phase; Physiological; Plant Resins; Plants; Play; Proanthocyanidins; Process; Prognosis; Property; Research; Role; Services; Source; Standardization; Structure; Structure-Activity Relationship; Testing; Tissues; Tooth Loss; Tooth structure; Treatment Cost; Work; base; common treatment; composite restoration; cost effective; dental resin; effectiveness study; improved; innovation; interfacial; mechanical properties; molecular shape; pain reduction; polyphenol; pre-clinical; procedure cost; response; restoration; restorative dentistry; seal; stereochemistry; three dimensional structure; tissue regeneration

SUMMARY The most conservative and common treatment of missing dental tissue is direct resin composite restoration. Its failure rate is high, lasting an average of 6 years. The primary reason for failure is the development of secondary caries. An estimated 50% of resin composite interventions replaces failed restorations, leading to a vicious restorative cycle with increasing complexity, poor prognosis for the tooth, and high treatment costs. Resin-based restorations rely on micro-mechanical adhesion to enamel and dentin structures. Dentin is of particular importance as it is the bulk of the tooth and tightly connected with the pulp tissue. It is well known that components of the dentin extracellular matrix play major roles in the formation and sustainability of the dentin-resin bonds. Bioinspired by natural dentin toughening mechanisms, our group identified refined mixtures and isolated proanthocyanidins (PACs), a 3D structurally diverse class of biosynthetic polyphenols that can mimic dentin natural processes. These molecules elicit enhancement to the mechanical properties and reduce matrix biodegradability, collectively termed dentin biomodification. Additionally, we have revealed that PACs can play multi-functional roles at the inherently wet dentin-resin interfaces. Therefore, PACs represent new biomaterials with promising impact in the broader field of restorative/reparative dentistry. Notably, the PAC sources of this project are renewable industrial waste and/or by-products, respectively, making them highly sustainable from both economic and environmental perspectives. The ultimate goal is to develop a mechanistically based and clinically feasible strategy to modulate permanent physico-mechanical properties of the dentin matrix, to create more stable dentin-resin bioadhesion, and thus increase the longevity of resin composite restorations. This will be accomplished by identifying features of specific molecules, ligand-PACs, that mediate stable biomodification and durable dentin-resin interfaces. More specifically, this project will define the structure activity relationships of ligand-PACs (a) to modulate the main components of dentin (extracellular matrix and mineral) sustainably; (b) to establish and optimize bioadhesion mechanisms at the dentin-PAC- resin interfaces; and (c) to tailor interfacial responses that directly affect performance and (pre-)clinical usage. The Specific Aims are: (Aim 1) Define distinct mechanisms of interactions of ligand-PACs with the extracellular matrix, mineral phase, and altered forms of dentin. (Aim 2) Elucidate and tailor ligand-PACs to produce robust biointerfaces. (Aim 3) Determine the stability of the tooth-PAC-resin interfaces in relevant microenvironments. The sustainable biomodification of the dental tissue will overcome clinical pitfalls associated with failure of tooth-resin interfaces, particularly dentin breakdown. The ultimate outcome is the development of a PAC-based intervention approach that can revolutionize dental restoration.

概括 缺失牙科组织的最保守和常见治疗方法是直接的树脂复合恢复。它是 失败率很高，平均持续6年。失败的主要原因是发展 次龋齿。估计有50％的树脂复合干预措施替代了失败的修复体，导致 恶性恢复周期，复杂性的增加，牙齿预后不良以及高度治疗成本。 基于树脂的修复体依赖于对搪瓷和牙本质结构的微机械粘附。牙本质是 特别重要的是，它是牙齿的大部分，并与纸浆组织紧密相连。众所周知 牙本质外基质的组成部分在形成和可持续性中起着重要作用 牙本质 - 树脂键。由天然牙本质韧性的生物启动，我们的小组确定了精制混合物 和分离的原腺苷（PACS），这是一种3D结构上多样的生物合成多酚，可以 模仿牙本质自然过程。这些分子引起机械性能的增强并降低 基质生物降解性，统称为牙本质生物修饰。此外，我们已经透露了PACS 可以在固有湿的牙本质 - 牙线界面上扮演多功能角色。因此，PACS代表新 生物材料在更广泛的恢复/修复牙科领域具有有希望的影响。值得注意的是PAC 该项目的来源分别是可再生的工业废物和/或副产品，使其高度高 从经济和环境的角度来看可持续。最终目标是开发 基于机械和临床可行的策略，以调节永久性物理机械特性 牙本质矩阵，以创建更稳定的牙本质 - 瑞胶生物粘附，从而增加树脂的寿命 复合修复体。这将通过识别特定分子，配体PAC的特征来实现 介导稳定的生物修饰和耐用的牙本质 - 瑞胶界面。更具体地说，这个项目将定义 配体-PAC（a）的结构活性关系调节牙本质的主要成分（细胞外 矩阵和矿物）可持续； （b）在牙本质-PAC-建立和优化生物粘附机制 树脂界面； （c）量身定制直接影响性能和（前）临床用法的界面反应。 具体目的是：（目标1）定义配体-PAC与细胞外相互作用的不同机制 基质，矿物相和牙本质的改变形式。 （AIM 2）阐明和量身定制配体-PAC可产生强大的 生物界面。 （AIM 3）确定相关微环境中牙齿 - 酸 - 牙界面的稳定性。 牙科组织的可持续生物修饰将克服与失败有关的临床陷阱 牙齿牙线界面，尤其是牙本质分解。最终结果是开发基于PAC的 可以彻底改变牙齿修复的干预方法。