Transdentinal Induction of Tertiary Dentin

描述（由申请人提供）：牙科修复的主要目标是 用与牙齿结构相似的材料替换龋齿结构 这种天然的矿化组织，同时保留了 牙髓牙本质复合体牙髓组织具有内在的防御机制 对抗最终导致新成牙本质细胞分化的损伤或损伤 和第三代牙本质的沉积。而反动派或 牙髓组织的修复性牙本质是对损伤的固有反应， 侮辱，它不是常规诱发现代临床治疗。我们的目标是 开发一种新的牙科材料， 来唤起这种生物学上有利的自我修复反应。研究表明 TGF-β家族的细胞因子，特别是骨形态发生因子， 蛋白质以及其他最近发现的矿化基质分子 (e.g.骨涎蛋白，牙釉原蛋白，牙本质涎磷蛋白，牙本质基质 蛋白1）能够诱导细胞增殖和/或表型变化， 牙髓细胞与修复过程中发生的细胞相当， 过程我们的假设是含有牙本质诱导因子的牙科材料 分子当被放置在腔体制备的地板上时将诱导三级 由下面的牙髓组织以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： AIM 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基因激活试验。具体目标 2将确定所鉴定的诱导分子的作用机制。 具体目标3将描述以下物质的最佳浓度和时程： 牙本质诱导分子对人牙本质细胞表型的影响 牙髓和成牙本质细胞的体外培养。具体目标4将决定 牙本质诱导分子的跨牙本质运动参数， 结合我们的环糊精载体系统在体外。虽然我们的目标和 假设没有改变，在这个延续的建议，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 牙本质诱导分子应该是容易获得的，应该有长期的 单独或与载体分子复合的生物活性，例如 环糊精，并具有优异的生物相容性。我们仍然致力于 经牙本质三级牙本质诱导成为 修复性牙科器械。

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.