Biomodification of Dentin Matrix Structure

描述（由申请人提供）：平均复合牙科修复体在5-7年内失效。失败的主要原因是在牙齿结构和修复体之间的界面处，并且经常导致继发龋。修复体的更换需要去除旧的，增加牙齿结构的损失，增加成本，并降低牙齿的预后。尽管在修复材料方面取得了广泛的进展，但在改善牙本质-树脂界面和最大限度地减少牙本质置换方面的成功仅限于材料本身的变化。本研究的最终目的是开发新的方法来提高牙本质基质的强度和稳定性，从而提高牙本质-树脂复合体的耐久性。初步研究为天然来源的试剂提供了强有力的支持，特别是富含多酚的植物提取物，其强烈增强牙本质基质性质并对牙本质-树脂键产生积极影响。这些试剂被提议作为牙本质基质的“生物修饰剂”。 这种应对临床挑战的创新方法可能为缺失牙齿结构的修复/修复治疗开辟新的前景。牙本质强度的增加似乎涉及牙本质有机成分和植物成分家族，低聚原花青素（OPC）之间的相互作用。OPC被广泛用作天然抗氧化剂，并已被证明在各种临床应用和草药膳食补充剂中是安全的。这个多学科的项目将集中在OPC和主要的牙本质基质成分之间的多功能相互作用所涉及的生物化学和生物力学，并调查牙本质-树脂键的形成和可持续性所涉及的参数。为此，主要假设是“生物修饰剂”和牙本质基质组分之间的多功能相互作用增强牙本质基质并导致牙本质-树脂界面的质量改善。此外，富含OPC的植物提取物的生物活性成分的植物化学分离和表征将导致更好地理解与牙本质基质相互作用的机制。综合结果将能够优化所需的牙本质活性和标准化的介入材料的潜在临床应用。具体目标是：目标1 -通过现代植物化学分析对具有确定的牙本质基质活性的富含OPC的天然提取物进行标准化;与目标2 -测定生物活性多酚/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）同时进行。目的3 -使用体外模型建立标准化介入材料的临床适用性，以确定牙本质生物改性的短期和长期恢复/修复益处。该项目代表了一种跨学科（牙科，药学）和创新的方法，以加强修复程序的牙本质基质基质。该结果有可能产生更持久的复合材料，最终可以改善医疗保健并降低医疗保健成本。

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.