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

基本信息

批准号：
10874883
负责人：
Ana Karina B Bedran-Russo
金额：
$ 49.6万
依托单位：
UNIVERSITY OF ILLINOIS AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-06-24 至 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10874883
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 Procedures Process Prognosis Property Research Role Services Source Standardization Structure Structure-Activity Relationship Testing Tissues Tooth Loss Tooth structure Treatment Cost Work common treatment composite restoration cost cost effective dental resin effectiveness study improved innovation interfacial mechanical properties molecular shape pain reduction polyphenol pre-clinical response restoration restorative dentistry seal stereochemistry tissue regeneration

项目摘要

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.

概括缺失牙组织最保守、最常见的治疗方法是直接树脂复合修复。它是故障率高，平均持续6年。失败的主要原因是开发继发性龋齿。据估计，50% 的树脂复合材料干预措施取代了失败的修复体，从而导致恶性修复循环，复杂性增加，牙齿预后差，治疗费用高。树脂修复体依赖于牙釉质和牙本质结构的微机械粘附。牙本质是特别重要，因为它是牙齿的主体并与牙髓组织紧密相连。众所周知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着重要作用牙本质-树脂键。受天然牙本质增韧机制的生物启发，我们的小组确定了精制混合物和分离的原花青素 (PAC)，一种 3D 结构多样化的生物合成多酚类，可以模仿牙本质的自然过程。这些分子可增强机械性能并减少基质生物降解性，统称为牙本质生物改性。此外，我们还透露 PAC 可以在固有湿润的牙本质-树脂界面上发挥多功能作用。因此，PAC 代表了新的在更广泛的修复/修复牙科领域具有前景的生物材料。值得注意的是，PAC 该项目的来源分别是可再生工业废物和/或副产品，这使得它们高度从经济和环境角度来看都是可持续的。最终目标是开发一个基于机械原理且临床可行的策略来调节永久物理机械特性牙本质基质，形成更稳定的牙本质-树脂生物粘附，从而延长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，介导稳定的生物改性和持久的牙本质-树脂界面。更具体地说，该项目将定义配体-PACs的结构活性关系（a）调节牙本质（细胞外）的主要成分基质和矿物质）可持续； (b) 建立并优化牙本质-PAC-的生物粘附机制树脂界面； (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）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。（目标 2）阐明并定制配体-PAC 以产生稳健的生物界面。（目标 3）确定相关微环境中牙齿-PAC-树脂界面的稳定性。牙组织的可持续生物改性将克服与牙体修复失败相关的临床缺陷牙齿-树脂界面，特别是牙本质破坏。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。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Proanthocyanidin Tetramers and Pentamers from Cinnamomum verum Bark and Their Dentin Biomodification Bioactivities.

肉桂树皮中的原花青素四聚体和五聚体及其牙本质生物改性生物活性。

DOI：
发表时间：
2022-02-25
期刊：
影响因子：
5.1
作者：
Jing, Shu;Alania, Yvette;Reis, Mariana;McAlpine, James B;Chen, Shao;Bedran;Pauli, Guido F
通讯作者：
Pauli, Guido F

B-type Proanthocyanidins with Dentin Biomodification Activity from Cocoa (Theobroma cacao).

来自可可（Theobroma cacao）的具有牙本质生物修饰活性的 B 型原花青素。

DOI：
发表时间：
2022-10-05
期刊：
影响因子：
6.1
作者：
Jing, Shu;Reis, Mariana;Alania, Yvette;McAlpine, James B;Chen, Shao;Bedran;Pauli, Guido F
通讯作者：
Pauli, Guido F

Surface-Directed Mineralization of Fibrous Collagen Scaffolds in Simulated Body Fluid for Tissue Engineering Applications.

用于组织工程应用的模拟体液中纤维胶原支架的表面定向矿化。

DOI：
10.1021/acsabm.0c01507
发表时间：
2021-03-15
期刊：
ACS applied bio materials
影响因子：
4.7
作者：
Bim-Júnior O;Curylofo-Zotti F;Reis M;Alania Y;Lisboa-Filho PN;Bedran-Russo AK
通讯作者：
Bedran-Russo AK

Modulatory role of terminal monomeric flavan-3-ol units in the viscoelasticity of dentin.

末端单体黄烷-3-醇单元在牙本质粘弹性中的调节作用。