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.

项目总结/文摘