Modularity in Oligomeric Phenol Chemistry for Biomodulation of Dental Structures

用于牙齿结构生物调节的低聚苯酚化学的模块化

• 批准号: 10604657
• 负责人: Ana Karina B Bedran-Russo
• 金额: $ 24.97万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-02-01 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10604657
• 关键词: Adhesions; Adhesives; Adopted; Aging; Anxiety; Biochemical; Biocompatible Materials; Biodegradation; Biological; Biological Response Modifiers; Biomechanics; Biomimetics; Carbon; Cells; Characteristics; Chemicals; Chemistry; Clinical; Collagen; Collagen Type I; Color; Complex; Data; Dental; Dental Care; Dental Enamel; Dental Pulp; Dental caries; Dentin; Dentistry; Development; Economics; Extracellular Matrix; Failure; Ferns; Foundations; Future; Goals; Health Care Costs; Healthcare; Human; Hydrogen Bonding; Incidence; Interdisciplinary Study; Intervention; Longevity; Mechanics; Methodology; Methods; Minerals; Molecular; Mouth Diseases; Natural Products; Natural Source; New Agents; Oral; Oral health; Outcome; Pattern; Performance; Personal Satisfaction; Pharmacy facility; Phase; Phenols; Phloroglucinol; Phytochemical; Plant Resins; Plant Sources; Plants; Play; Polymers; Population; Proanthocyanidins; Property; Role; Skeleton; Solid; Source; Structural Protein; Structure; Surface; Tannic Acid; Therapeutic; Tissues; Tooth structure; Vascular Plant; Vitis; biomaterial compatibility; biomechanical test; clinical application; dental structure; design; dimer; improved; innovation; insight; novel; oral infection; oxidation; pain reduction; polymerization; preclinical development; preclinical study; premature; restoration; restorative dentistry; scaffold; soft tissue; tool

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.

项目概要/摘要 龋齿是一种几乎普遍存在的传染性口腔疾病，对人类健康有着巨大的直接和间接影响 护理、福祉、劳动力和经济。牙科修复干预措施的质量和寿命 很大程度上取决于牙本质的完整性和生物力学特性，牙本质是牙齿的软组织，在很大程度上 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 依赖于胶原牙本质结构的微机械粘附。我们的跨学科研究团队拥有 提供了低聚原花青素作为新型生物活性材料来源的广泛证据 来自植物。这些数据支持了仿生策略的可行性，该策略可提高 基于粘合剂的修复体。从基础临床前研究中获得的见解使人们认识到 模块化低聚植物酚（MOPP）作为与以下物质相互作用的化合物的共同结构基序 结构蛋白，例如胶原蛋白。由单独的探索性植物化学和生物力学支持 研究并考虑结构特征，该项目旨在探索两种生物学 MOPP、维管植物中的二苯乙烯类化合物和间苯三酚尚未被研究，但化学性质多样 来自蕨类植物，作为潜在的有希望的额外线索。核心假设是中等低聚二苯乙烯类化合物 和间苯三酚具有相似但明显不同的结构特征，使得这些 MOPP 适用于牙本质生物调节和生物/生物力学研究的正交工具。总体目标 是用以前未（未）探索的化学多样性结构类别来扩展牙科工具箱 具有模块化构建模式的生物调节剂。 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 交互式方法的生物材料角度：（目标 1）来源、纯化和表征新的模块化 低聚植物酚（MOPP）； （目标 2）建立并比较 MOPP 与 人类牙齿成分（牙釉质、牙本质和牙髓细胞）。采用创新的净化和先进的 复杂 MOPP 的结构表征方法并执行其并行的最新技术 生物力学评估，该项目具有利用结构复杂性并定义 实用和模块化的天然生物调节剂。引入 MOPP 自然模块化的潜力 定制生物调节疗法并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 二苯乙烯类化合物和间苯三酚作为尚未开发的生物活性剂的应用。最终项目成果 是建立新类别的 MOPP 作为未来临床前开发的组织生物调节剂。