Modularity in Oligomeric Phenol Chemistry for Biomodulation of Dental Structures

项目摘要/摘要 龋病是一种几乎无处不在的传染性口腔疾病，对人类健康有巨大的直接和间接影响。 关怀、福祉、劳动力和经济。牙科修复术的质量和寿命 这在很大程度上取决于牙本质的完整性和生物力学特性，牙本质的大部分软组织 由I型胶原蛋白和矿物质组成。广泛使用的树脂基修复体的形成和可持续性 依靠微机械黏附于牙本质的胶原层结构。我们的跨学科研究团队已经 为低聚原花青素作为新的生物活性材料来源的用途提供了广泛的证据 从植物中。这些数据支持仿生策略的可行性，该策略可以增强 粘合剂基修复体。从基础的临床前研究中获得的见解导致了对 模块化低聚植物酚(MOPPS)作为与之相互作用的化合物的共同结构基序 结构蛋白，如胶原蛋白。由单独探索的植物化学和生物力学支持 在研究和考虑结构特征的同时，这个项目试图从生物学上探索两个 未被研究的类别但化学上不同的MOPPS、来自维管植物的二苯乙烯类化合物和间苯三酚 来自蕨类植物，作为潜在的有希望的额外线索。核心假设是中低聚二苯乙烯类化合物 而间苯三酚具有相似但截然不同的结构特征，使这些MOPPS 适用于牙本质生物调节和生物/生物力学研究的正交工具。首要目标是 是扩展牙科工具箱与以前未探索的化学多样性的结构类别 具有模块化构建模式的生物调节器。 接近牙科-药学界面的总体假设，这两个目标反映了植物分析 和互动方法的生物材料角度：(目标1)来源、提纯和表征新的模块 低聚植物酚(MOPPS)；(目标2)建立和比较MOPPS与 人体牙齿成分(牙釉质、牙本质和牙髓细胞)。采用创新的净化和高级 复杂MOPPS的结构表征方法及其并行研究进展 生物力学评估，该项目具有显著的能力来驾驭结构的复杂性和定义 实用和模块化的天然生物调节剂。引入MOPPS的自然模块化的可能性 量身定制的生物调节疗法和增强其临床适用性是该项目的创新方面。 这些研究将为潜在的口腔生物医学奠定坚实的植物化学和生物学基础 二苯乙烯类和间苯三酚作为未被开发的生物活性物质的应用。最终的项目成果 是建立新类别的MOPPS作为组织生物调节剂，用于未来的临床前开发。

Project Summary/Abstract Caries is a near-ubiquitous infectious oral disease with an enormous direct and indirect impact on human health care, well-being, workforce, and the economy. The quality and longevity of dental restorative interventions depend largely on the integrity and biomechanical properties of dentin, the tooth’s bulk soft tissue that largely consists of type I collagen and mineral. Formation and sustainability of the widely used resin-based restorations rely on micro-mechanical adhesion to the collagenous dentin structures. Our interdisciplinary research team has produced extensive evidence for the utility of oligomeric proanthocyanidins as novel bioactive materials sources from plants. This body of data supports the feasibility of a biomimetic strategy that enhances the performance of adhesive-based restorations. Insights gained from the underlying pre-clinical studies led to the recognition of modular oligomeric plant phenols (MOPPs) as the common structural motif of compounds that interact with structural proteins such as collagen. Supported by separate exploratory phytochemical and biomechanical studies as well as considering structural characteristics, this project seeks to explore two biologically understudied classes yet chemically diverse of MOPPs, stilbenoids from vascular plants and phloroglucinols from ferns, as potentially promising additional leads. The core hypothesis is that medium-oligomeric stilbenoids and phloroglucinols have analogous yet distinctly different structural characteristics that make these MOPPs suitable for dentin biomodulation and orthogonal tools for biological/biomechanical studies. The overarching goal is to extend the dentistry toolbox with previously un(der)explored structural classes of chemically diverse biomodulators with modular build patterns. Approaching the overall hypothesis at the dentistry-pharmacy interface, the two Aims reflect the phytoanalytical and biomaterial angles of an interactive approach: (Aim 1) Source, purify, and characterize new modular oligomeric plant phenols (MOPPs); (Aim 2) Establish and compare mechanisms of interactions of MOPPs with human teeth constituents (enamel, dentin and pulp cells). Employing innovative purification and advanced structural characterization methodologies for the complex MOPPs and performing their parallel state-of-the-art biomechanical evaluation, the project has significant ability to harness the structural complexity and define the utility and modular natural biomodulation agents. The potential to introduce natural modularity of MOPPs for tailored biomodulatory therapeutics and enhance their clinical applicability are innovative aspects of the project. The studies will build a solid phytochemical and biological foundation for the potential oral biomedical applications of stilbenoids and phloroglucinols as underexplored bioactive agents. The ultimate project outcome is the establishment of new classes of MOPPs as tissue biomodulators for future preclinical development.