Transdentinal Induction of Tertiary Dentin

三级牙本质穿牙诱导

• 批准号: 6443102
• 负责人: Mary MacDougall
• 金额: $ 17.41万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-06-01 至 2007-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6443102
• 关键词: biomaterial development /preparation; bone morphogenetic proteins; cell differentiation; cell line; cyclodextrins; cytokine; cytokine receptors; dental materials; dental pulp; dentin; dentinogenesis; drug delivery systems; extracellular matrix; human tissue; odontoblasts; regeneration; restorative dentistry

DESCRIPTION (provided by applicant): A major goal of restorative dentistry is the replacement of carious tooth structure with materials that closely resemble that natural mineralized tissue, while preserving the vitality of the pulpo-dentinal complex. Pulp tissue exhibits an intrinsic defense mechanism against insult or injury culminating in the differentiation of new odontoblasts and the deposition of tertiary dentin. While the formation of reactionary or reparative dentin by the pulp tissue is an inherent response to injury or insult, it is not routinely evoked in modern clinical treatments. Our goal is to develop a new dental material that can be applied to the floor of a cavity to evoke this biologically favorable response of self-healing. Studies suggest that cytokines of the TGF-beta family, in particular bone morphogenetic proteins, as well as other, recently identified mineralized matrix molecules (e.g. bone sialoprotein, amelogenin, dentin sialophosphoprotein, dentin matrix protein 1) are capable of inducing proliferative and/or phenotypic changes in dental pulp cells that are comparable to those occurring during the reparative process. Our hypothesis is that dental material containing dentin-inducing molecules when placed on the floor of a cavity preparation will induce tertiary dentin formation by the underlying dental pulp tissue in a predictable manner. To test this hypothesis, we propose the following four specific aims: Specific Aim 1 will use newly developed human dental cell lines to screen potential dentin-inductive molecules in a novel DSPP gene activation assay. Specific Aim 2 will determine the mechanism of action of identified inductive molecules. Specific Aim 3 will characterize the optimal concentration and time-course of promising dentin inductive molecules on the phenotypic changes in human dental pulp and odontoblast cells in vitro. Specific Aim 4 will determine the parameters of transdentinal movement of the dentin inductive molecules in combination with our cyclodextrin carrier system in vitro. While our goal and hypothesis have not changed in this continuation proposal, we have broadened our scope to a more general survey of suitable dentin-inductive molecules to be used in combination with our novel restorative system. The ideal dentin-inductive molecule should be readily available, should have prolonged biological activity either alone or in complex with carrier molecules like cyclodextrins, and have excellent biocompatibility. We remain committed to see transdentinal tertiary dentin induction becoming an integral part of the restorative dental armentarium.

描述(申请人提供)：修复体牙科的一个主要目标是 用相似的材料替换龋齿结构 这种天然矿化组织，在保持生命力的同时 牙髓-牙本质复合体。牙髓组织表现出一种内在的防御机制 对抗侮辱或损伤，最终导致新的成牙本质细胞分化 三级牙本质沉积。反动派或反动派的形成 由牙髓组织修复的牙本质是对损伤或 侮辱，在现代临床治疗中不是常规的唤起。我们的目标是 开发一种可应用于龋齿底部的新牙科材料 以唤起这种对自我修复的生物学上有利的反应。研究表明 转化生长因子-β家族的细胞因子，特别是骨形态发生 蛋白质以及其他新近发现的矿化基质分子 (如骨涎蛋白、釉原蛋白、牙本质涎磷蛋白、牙本质基质 蛋白1)能够诱导细胞增殖和/或表型改变 牙髓细胞与修复过程中发生的细胞相当 进程。我们的假设是含有牙本质诱导性的牙科材料 当分子被放置在空洞制备的地板上时，将导致第三次 牙髓组织以一种可预测的方式形成牙本质。 为了验证这一假设，我们提出了以下四个具体目标： 目标1将使用新开发的人类牙齿细胞系来筛选潜在的 牙本质诱导分子在一种新的DSPP基因激活分析中的应用。特定目标 2将确定已识别的诱导分子的作用机制。 具体目标3将描述最佳浓度和时间进程 牙本质诱导分子在人类牙齿表型变化中的应用前景 牙髓和成牙本质细胞的体外培养。具体目标4将决定 牙本质诱导分子在牙本质中的牙本质运动参数 与我们的环糊精载体系统在体外结合。虽然我们的目标和 假设没有改变，在这个延续方案中，我们扩大了 我们的范围是对合适的牙本质诱导分子进行更全面的调查 与我们的新型修复系统结合使用。理想 牙本质诱导分子应易于获得，应延长 单独或与载体分子形成络合物的生物活性 环糊精，并具有良好的生物相容性。我们将继续致力于 经牙本质三级牙本质诱导成为牙本质修复的组成部分 修复式牙科医疗设备。