TRANSDENTINAL INDUCTION OF TERTIARY DENTIN

三级牙本质的经牙本质诱导

• 批准号: 6443361
• 负责人: Mary MacDougall
• 金额: $ 40.85万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-01 至 2003-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6443361
• 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.

修复性牙科的一个主要目标是取代龋齿 牙齿结构，其材料最接近于天然的 矿化组织，同时保持生命力 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，最终导致 成牙本质细胞分化与“三级”牙本质沉积 我们的目标是开发一种新的牙科材料，当应用于 一个洞的底部会导致一个可预见的生物学上有利的 反应导致第三牙本质的形成。我们把我们的目标建立在 细胞因子成骨蛋白-1(0p-I，BMP-7)的观察 是形态发生的，导致增殖和表型变化 在牙髓细胞中。我们的假设是一种牙科材料 当将含有OP-I的物质放置在空洞制备的地板上时 引起三级牙本质形成的可预测的生物学反应 在牙髓组织内。为了检验这一假设，我们将 追求五个具体目标。特定的#1将标识细胞表面 S的OP-I受体，并对其生物学特性进行了研究。 对这一目标至关重要的是对受体的表征 这些细胞因子存在于成牙本质细胞和牙髓细胞群体中。 具体目标2将确定最优条件 OP-I对牙本质细胞外刺激的诱导作用 基质产生与牙髓细胞分化为 正常的成牙本质细胞。药剂用量参数的确定 体内研究将通过获得一种独特的 单层细胞培养系统及永生化牙髓 和成牙本质细胞系已经在我们的 实验室。具体目标#3将确定以下参数 0p-1在体外对流和弥散的牙本质运动。 这一目标将估计需要的细胞因子浓度在 表面，以便提供在体内建立的适当剂量 特定目标#1.在特定目标#4中，我们将开发凝胶或溶液 以主动形式结合0P-1的传送系统，用于 运送到地面的空洞制备，这不会干扰 以及随后应用的修复材料的粘结。我们 将把我们的调查重点放在短期内的交付系统上 放手。我们的最后一个具体目标#5将决定 牙本质诱导型OP-I牙髓组织修复衬垫的体内研究。 这将通过测量在体内的迁移来实现 细胞因子(S)牙本质内注射与促有丝分裂作用的测定 这些分子中。我们期望通过牙本质的 第三代牙本质的诱导将成为 通过适当融合碱性牙体修复牙体美容 细胞和分子生物学和牙科材料。