Dentin Biomodification for Optimization of Bioadhesive Dental Restorations

总结 缺失牙体组织的最保守和最常见的治疗方法是直接树脂复合修复。其 故障率高，平均持续6年。失败的主要原因是 继发龋据估计，50%的树脂复合材料干预措施取代了失败的预防措施， 恶性修复循环，复杂性增加，牙齿预后差，治疗费用高。 树脂基牙釉质依赖于对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，与牙髓组织紧密相连。众所周知的是 牙本质细胞外基质的成分在牙本质的形成和可持续性中起着重要作用， 牙本质-树脂粘结剂受天然牙本质增韧机制的生物启发，我们的研究小组确定了精细的混合物 和分离的原花青素（PAC），一种3D结构多样的生物合成多酚类， 模仿牙本质的自然过程。这些分子引起机械性能的增强，并降低 基质生物降解性，统称为牙本质生物改性。此外，我们还发现，PAC 可在固有湿润的牙本质-树脂界面发挥多功能作用。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。特别是，PAC 该项目的资源是可再生的工业废物和/或副产品，分别，使他们高度 从经济和环境的角度来看。最终目标是开发一个 基于机械的临床可行策略，以调节 牙本质基质，以产生更稳定的牙本质-树脂生物粘附，从而增加树脂的寿命 复合材料这将通过鉴定特定分子，配体-PAC， 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-PAC的结构活性关系（a）调节牙本质的主要成分（细胞外 （B）建立和优化牙本质-PAC-的生物粘附机制。 树脂界面;和（c）定制直接影响性能和（预）临床使用的界面响应。 具体目的是：（目的1）确定配体-PAC与细胞外基质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）阐明和定制配体-PAC以产生稳健的 生物界面(Aim 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改性将克服与牙齿修复失败相关的临床缺陷。 牙齿-树脂界面，特别是牙本质破裂。最终的结果是开发一个基于PAC的 介入方法，可以彻底改变牙齿修复。

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.