Biomodification of Dentin Matrix Structure

牙本质基质结构的生物改性

• 批准号: 8525113
• 负责人: Ana Karina B Bedran-Russo
• 金额: $ 33.91万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8525113
• 关键词: Adhesions; Adhesives; Antioxidants; Applied Research; Basic Science; Biochemistry; Biocompatible Materials; Biodegradation; Biological; Biological Assay; Biological Factors; Biomechanics; Chemicals; Clinical; Collagen; Collagen Type I; Complex; Confocal Microscopy; Dental caries; Dentin; Dentistry; Detection; Development; Differential Scanning Calorimetry; Electrons; Excision; Extravasation; Failure; Family; Fractionation; Goals; Health Care Costs; Healthcare; Knowledge; Lasers; Lead; Longevity; Matrix Metalloproteinases; Measurement; Mechanics; Methods; Microscopy; Nature; Nuclear Magnetic Resonance; Oral health; Outcome; Performance; Pharmacognosy; Pharmacologic Substance; Pharmacy facility; Phytochemical; Plant Extracts; Plant Resins; Play; Proanthocyanidins; Procedures; Property; Proteoglycan; Role; Standardization; Structure; Technology; Time; Tissues; Tooth structure; Translating; Translational Research; analytical method; base; biological standardization; clinical application; clinically relevant; composite restoration; cost; design; dietary supplements; improved; in vitro Model; innovation; multidisciplinary; nano; outcome forecast; polyphenol; restoration; restorative dentistry; restorative material; seal; success; translational approach; Adhesions; Adhesives; Antioxidants; Applied Research; Basic Science; Biochemistry; Biocompatible Materials; Biodegradation; Biological; Biological Assay; Biological Factors; Biomechanics; Chemicals; Clinical; Collagen; Collagen Type I; Complex; Confocal Microscopy; Dental caries; Dentin; Dentistry; Detection; Development; Differential Scanning Calorimetry; Electrons; Excision; Extravasation; Failure; Family; Fractionation; Goals; Health Care Costs; Healthcare; Knowledge; Lasers; Lead; Longevity; Matrix Metalloproteinases; Measurement; Mechanics; Methods; Microscopy; Nature; Nuclear Magnetic Resonance; Oral health; Outcome; Performance; Pharmacognosy; Pharmacologic Substance; Pharmacy facility; Phytochemical; Plant Extracts; Plant Resins; Play; Proanthocyanidins; Procedures; Property; Proteoglycan; Role; Standardization; Structure; Technology; Time; Tissues; Tooth structure; Translating; Translational Research; analytical method; base; biological standardization; clinical application; clinically relevant; composite restoration; cost; design; dietary supplements; improved; in vitro Model; innovation; multidisciplinary; nano; outcome forecast; polyphenol; restoration; restorative dentistry; restorative material; seal; success; translational approach

DESCRIPTION (provided by applicant): The average composite dental restoration fails within 5-7 years. The primary cause of failure is at the interface between tooth structure and the restoration, and frequently results in secondary caries. Replacement of the restoration requires the removal of the old, increased loss of tooth structure, increased cost, and a decreased prognosis for the tooth. Despite extensive advances in restorative materials, success in improving the dentin-resin interface and minimizing replacement of restorations has been limited to changes to the material itself. The ultimate goal of this proposal is to develop new methods to improve dentin matrix strength and stability, and thereby enhance the durability of dentin-resin restorations. Preliminary studies provide strong support for nature-derived agents, in particular polyphenol-rich plant extracts, which strongly enhance dentin matrix properties and positively impact the dentin-resin bonds. These agents are proposed as "biomodifiers" of dentin matrix. This innovative approach to the clinical challenge may open new perspectives for restorative/reparative therapies of lost tooth structure. The demonstrated increase in dentin strength appears to involve interactions between dentin organic components and a family of phytoconstituents, the oligomeric proanthocyanidins (OPCs). OPCs are broadly used as natural antioxidants and have proven to be safe in various clinical applications and in herbal dietary supplements. This multidisciplinary project will focus on the biochemistry and biomechanics involved in the multi-functional interactions between OPC and major dentin matrix components, and investigates parameters involved in the formation and sustainability of dentin- resin bonds. To this end, the main hypothesis is that multi-functional interactions between the "biomodifiers" and dentin matrix components enhance the dentin matrix and result in quality improvement of the dentin-resin interface. In addition, phytochemical isolation and characterization of the bioactive ingredients of OPC-rich plant extracts will lead to a better understanding of the mechanisms of interaction with the dentin matrix. Combined results will enable optimization of desirable dentin activity and standardization of an interventional material for potential clinical application. The Specific Aims are: Aim 1 - Standardization of an OPC-rich natural extract with defined dentin matrix activity by means of modern phytochemical analysis; performed in tandem with Aim 2 - Determination of the short- and long-term interactions of bioactive polyphenols/OPC with the organic dentin matrix (collagen, proteoglycans, matrix metalloproteinases), as it relates to strength and stability of the tissue. Aim 3 - Establishment of clinical applicability of a standardized interventional material using in vitro models to determine both short and long-term restorative/reparative benefits of dentin biomodification. The project represents an inter-disciplinary (dentistry, pharmacy) and innovative approach to strengthening the dentin matrix substrate for restorative procedures. The outcome has potential to produce longer-lasting composite restorations, which can ultimately improve health care and reduce health care costs.

描述（由申请人提供）：平均复合牙齿修复在5 - 7年内失败。失败的主要原因是牙齿结构和修复之间的界面，并且经常导致龋齿。替代恢复需要清除牙齿结构的旧损失，成本增加以及牙齿预后减少。尽管恢复材料方面取得了广泛的进步，但在改善牙本质 - 牙线界面和最大程度地替代修复体方面的成功限于材料本身的变化。该提案的最终目标是开发新的方法来改善牙本质基质强度和稳定性，从而提高牙本质 - 瑞星修复体的耐用性。初步研究为自然衍生的剂，尤其是富含多酚的植物提取物提供了强有力的支持，这些植物提取物强烈增强了牙本质基质特性，并对牙本质 - 牙质键产生积极影响。这些药物被提出为牙本质基质的“生物改装剂”。 这种针对临床挑战的创新方法可能会为失去牙齿结构的修复/修复疗法提供新的观点。证明牙本质强度的提高似乎涉及牙本质有机成分与植物成分家族之间的相互作用，即寡聚性原蛋白蛋白（OPC）。 OPC被广泛用作天然抗氧化剂，已被证明在各种临床应用和草药饮食补充剂中都是安全的。这个多学科项目将重点关注OPC和主要牙本质基质组件之间多功能相互作用的生物化学和生物力学，并研究参与牙本质键形成和可持续性的参数。为此，主要的假设是“生物改装剂”和牙本质基质成分之间的多功能相互作用增强了牙本质基质，并导致牙本质星子界面的质量提高。此外，富含OPC的植物提取物生物活性成分的植物化学分离和表征将更好地理解与牙本质基质的相互作用机制。结合结果将使理想的牙本质活性和介入材料的标准化优化，以进行潜在的临床应用。具体目的是：AIM 1-通过现代植物化学分析，具有定义的牙本质基质活性的富含OPC的天然提取物的标准化；与AIM 2进行串联进行 - 确定生物活性多酚/OPC与有机牙本质基质（胶原蛋白，蛋白聚糖，基质金属蛋白酶）的短期和长期相互作用，因为它与组织的强度和稳定性有关。目标3-使用体外模型确定标准化介入材料的临床适用性，以确定牙本质生物修饰的短期和长期修复/修复益处。该项目代表了一种跨学科（牙科，药房）和创新方法，用于加强牙本质基质底物进行修复程序。结果有可能产生更长的综合修复体，这最终可以改善医疗保健并降低医疗保健成本。