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: 10397165
• 负责人: Ana Karina B Bedran-Russo
• 金额: $ 50.96万
• 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/10397165
• 关键词: 3-Dimensional; 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; 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.

摘要 牙体组织缺失最保守、最常见的治疗方法是直接树脂复合体修复。它的 失败率高，平均持续6年。失败的主要原因是 继发性龋齿。据估计，50%的树脂复合体介入治疗取代了失败的修复，导致 恶性修复循环，复杂性增加，牙齿预后差，治疗费用高。 树脂基修复体依赖于牙釉质和牙本质结构的微机械粘接。牙本质是 尤其重要，因为它是牙齿的主体，与牙髓组织紧密相连。这是众所周知的 牙本质细胞外基质的成分在牙本质细胞外基质的形成和可持续性中发挥重要作用 牙本质-树脂粘结剂。受天然牙本质增韧机制的生物启发，我们小组确定了精制的混合物 以及分离的原花青素(PAC)，这是一种3D结构多样化的生物合成多酚，可以 模拟牙本质的自然过程。这些分子导致力学性能的提高和降低 基质生物降解性，统称为牙本质生物修饰。此外，我们还透露，政治行动委员会 可在天然湿润的牙本质-树脂界面起到多功能作用。因此，政治行动委员会代表着新的 在更广泛的修复/修复牙科领域具有良好影响的生物材料。值得注意的是，政府账目委员会 该项目的来源分别是可再生工业废物和/或副产品，使它们高度 从经济和环境两个角度来看都是可持续的。最终目标是开发一个 以力学为基础和临床可行的策略来调节永久化的物理机械性能 牙本质基质，能产生更稳定的牙本质-树脂生物粘附力，从而增加树脂的寿命 复合修复体。这将通过鉴定特定分子、配体-PAC、 可调节稳定的生物修复和耐用的牙本质-树脂界面。更具体地说，这个项目将定义 配基-PAC(A)调节牙本质主要成分(细胞外)的构效关系 可持续地)；(B)建立和优化牙本质-PAC- 树脂界面；以及(C)定制直接影响性能和(临床前)使用的界面反应。 具体目标是：(目标1)确定配体-PAC与细胞外相互作用的不同机制 基质、矿物相和改变形式的牙本质。(目标2)阐明和定制配体-PAC以产生健壮的 生物界面。(目的3)测定牙齿-PAC-树脂界面在相关微环境中的稳定性。 牙齿组织的可持续生物降解将克服与失败相关的临床陷阱 牙齿-树脂界面，特别是牙本质破裂。最终结果是发展一个以PAC为基础的 可以革命性地改变牙齿修复的干预方法。