TRANSDENTINAL INDUCTION OF TERTIARY DENTIN

三级牙本质的经牙本质诱导

• 批准号: 6104911
• 负责人: Mary MacDougall
• 金额: $ 16.8万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-04-01 至 2000-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6104911
• 关键词: biomaterial development /preparation; cell differentiation; cell line; cytokine; cytokine receptors; dental materials; dental pulp; dentin; dentinogenesis; drug delivery systems; extracellular matrix; odontoblasts

A major goal of restorative dentistry is the replacement of carious tooth structure with a material that most closely resembles the natural mineralized tissue, while at the same time preserving the vitality of the pulpo-dentinal complex. pal tissue exhibits an intrinsic defense mechanism against insult or injury which culminates in the differentiation of odontoblasts and the deposition of "tertiary" dentin. Our goal is to develop a new dental material that when applied to the floor of a cavity will induce a predictable biologically favorable response resulting in tertiary dentin formation. We base our goal on the observations that the cytokine osteogenic protein 1(0P-I, BMP 7) is morphogenetic, inducing both proliferative and phenotypic changes in dental pulp cells. Our hypothesis is that a dental material containing OP-I when placed in the floor of a cavity preparation will evoke a predictable biological response of tertiary dentin formation within the dental pulp tissue. In order to test this hypothesis, we will pursue five Specific Aims. Specific #1 will identify the cell surface receptor(s) for OP-I and characterize their biological properties. Critical to this aim will be the characterization of the receptors for these cytokines within odontoblast and dental pulp cell populations. Specific Aim #2 will determine the optimal conditions for the inductive effect of OP-I in vitro on stimulation of dentin extracellular matrix production and the cytodifferentiation of dental pulp cells into functional odontoblasts. Determination of the dosage parameters for in vivo studies will be facilitated by the availability of an unique monolayer cell culture system as well as immortalized dental pulp and odontoblast cell lines which have been established in our laboratory. Specific Aim #3 will determine the parameters of convective and diffusive transdentinal movement of 0P-1 in vitro. This aim will estimate the concentration of cytokine needed at the surface, in order to deliver the proper dose established in the Specific Aim #1. In Specific Aim #4, we will develop gel or solution delivery system which incorporates 0P-1 in an active form for transport to the floor of a cavity preparation, which will not interfere with the bonding of subsequently applied restorative materials. We will focus our investigation on delivery systems with a short-term release. Our last Specific Aim #5 will determine the effects of the dentin-inductive OP-I restorative liner on dental pulp tissue in vivo. This will accomplished by measuring the in vivo migration of cytokine(s) transdentinally and determination of the mitogenic effects of these molecules. It is our expectation that the transdentinal induction of tertiary dentin will become an integral part of the restorative dental armentarium through the proper fusion of basic cellular and molecular biology and dental materials.

修复牙科的一个主要目标是替换龋齿 牙齿结构的材料，最接近自然的 矿化组织，同时保持活力， 牙髓牙本质复合体PAL组织表现出一种内在的防御 防止侮辱或伤害的机制， 成牙本质细胞的分化和“三级”牙本质的沉积。 我们的目标是开发一种新的牙科材料， 腔底将诱导可预测的生物有利的 反应导致三级牙本质形成。我们的目标是 观察到细胞因子成骨蛋白1（0 P-I，BMP 7） 是形态发生的，诱导增殖和表型变化 在牙髓细胞中。我们的假设是一种牙科材料 当将含有OP-I的药物置于腔体制备的底部时， 引起三级牙本质形成可预测的生物反应 在牙髓组织中。为了验证这个假设，我们将 追求五个具体目标。特异性#1将识别细胞表面 OP-I的受体，并表征其生物学特性。 这一目标的关键将是表征受体， 这些细胞因子存在于成牙本质细胞和牙髓细胞群中。 具体目标#2将确定 OP-I对牙本质细胞外刺激诱导作用 基质的产生和牙髓细胞向 功能性成牙本质细胞剂量参数的确定 体内研究将通过提供独特的 单层细胞培养系统以及永生化牙髓 和成牙本质细胞系， 实验室具体目标#3将确定 0 P-1在体外的对流和扩散的跨牙本质运动。 这一目的将估计细胞因子的浓度需要在 表面，以提供适当的剂量建立在 具体目标#1。在具体目标#4中，我们将开发凝胶或溶液 输送系统以活性形式结合了0 P-1， 运输到洞准备的地板上，这不会干扰 与随后应用的修复材料粘合。我们 将集中我们的调查与短期的交付系统 release.我们的最后一个具体目标#5将决定的影响， 牙本质诱导型OP-I修复衬垫对牙髓组织的影响。 这将通过测量以下物质的体内迁移来实现： 细胞因子和促有丝分裂作用的测定 of these molecules分子. 我们希望， 三级牙本质的诱导将成为 通过适当融合的基本修复牙科设备 细胞和分子生物学以及牙科材料。