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.

项目摘要/摘要 龋齿是一种近乎血统的传染性口腔疾病，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，牙齿的大块软组织很大程度上取决于 由I型胶原蛋白和矿物组成。广泛使用的基于树脂的修复体的形成和可持续性 依靠微机械粘合剂对胶原牙本质结构。我们的跨学科研究团队有 产生了广泛的证据证明寡聚性原腺苷作为新型生物活性材料来源的实用性 来自植物。该数据主体支持仿生策略的可行性，从而提高了性能 基于粘合剂的修复体。从基础临床前研究中获得的见解导致人们认识到 模块化寡聚植物酚（MOPP）作为与 结构蛋白，例如胶原蛋白。由单独的探索性理化和生物力学支持 研究以及考虑结构特征，该项目试图在生物学上探索两个 研究的类尚未化学的MOPPS，来自血管植物和菲洛格葡萄糖的Silbenoids 从蕨类植物，作为潜在有希望的其他潜在客户。核心假设是中等寡聚类男性类 硫葡萄醇具有类似但明显不同的结构特征，使这些mopps 适用于生物/生物力学研究的牙本质生物调制和正交工具。总体目标 是通过以前（der）探索的化学多样性的结构类别扩展牙科工具箱 具有模块化构建模式的生物调节剂。 接近牙科 - 药物界面的总体假设，这两个目的反映了植物分析 和交互式方法的生物材料角度：（目标1）源，净化和表征新的模块化 寡聚植物苯酚（MOPPS）； （AIM 2）建立和比较MOPP相互作用的机制 人牙一致（搪瓷，牙本质和果肉细胞）。采用创新净化和高级 复杂MOPP的结构表征方法并执行其平行最新的方法 生物力学评估，该项目具有利用结构复杂性并定义的重要能力 实用程序和模块化天然生物调制剂。引入MOPP的自然模块的潜力 量身定制的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服生物医学建立坚实的物理和生物基础 Silbenoids和磷酸葡萄醇作为未置换的生物活性剂的应用。最终项目结果 是建立新的MOPP，作为将来临床前开发的组织生物调节剂。