Mechanisms of Cell/Surface Interaction

描述（由申请人提供）：我们的总体目标是了解决定细胞和组织如何对植入材料作出反应的机制，以改善临床使用的器械和组合产品的功能。使用钛（Ti）基材的研究表明，通过了解表面形态和化学如何调节细胞反应，有可能开发出通过结构信号控制细胞行为的材料，而无需进行药理学修饰。本提案的目的是使用结构化材料表面来定义哪些微米级和亚微米级形貌特征调节特定的细胞反应，并理解所涉及的潜在机制。通过控制表面化学，我们还将研究微结构和亲水性如何相互作用来控制细胞行为。我们的长期目标是创造合理的仿生植入物，促进正常组织再生和修复。我们的实验假设是，表面的物理和化学性质决定整合素的表达，影响细胞信号传导和对调节骨生成的因子的反应，如1，25-二羟基维生素D3 [1，25（OH）2D 3]和雌激素。我们将检查成骨细胞的行为，使用电化学微加工制备的钛表面，以产生微米级的结构特征;亚微米级的形貌将叠加在受控条件下化学蚀刻的表面。基底将被设计成具有可比较的微结构但具有不同的亲水性。细胞培养模型包括：人成骨细胞样MG 63细胞、正常人成骨细胞（NHOst细胞）和大鼠成骨细胞样细胞系ROS 17/2.8。提出了三个具体目标：检查整合素在介导表面设计特征对成骨细胞表型表达的差异效应中的作用。Aim II.检查底物结构在成骨细胞对1，25（OH）2D 3和17 b-雌二醇的反应中的作用。Aim III.检查整合素信号传导在介导表面设计和类固醇激素作用对成骨细胞表型表达的协同作用中的作用。因此，虽然我们的实验是基本的性质，我们的目的是进行他们的方式，结果可以应用于临床种植学和组织工程。

DESCRIPTION (provided by applicant): Our overall goal is to understand the mechanisms that determine how cells and tissues respond to implanted materials in order to improve the function of devices and combination products used clinically. Studies using titanium (Ti) substrates suggest that by understanding how surface morphology and chemistry modulate cell response, it may be possible to develop materials that control cell behavior through structural signaling, without the need for pharmacologic modification. The purpose of the present proposal is to use structured material surfaces to define which micron-scale and sub-micron scale topographical features regulate specific cell responses and to understand the underlying mechanisms involved. By controlling surface chemistry, we will also investigate how microarchitecture and hydrophilicity interact to control cell behavior. Our long term goal is to create rational biomimetic implants that facilitate normal tissue regeneration and repair. Our experimental hypothesis is that the physical and chemical properties of a surface determine integrin expression, influencing cellular signaling and response to factors that regulate osteogenesis, such as 1,25- dihydroxy vitamin D3 [1,25(OH)2D3] and estrogen. We will examine osteoblast behavior on defined Ti surfaces prepared using electochemical micromachining to produce micrometer scale structural features; submicron scale topography will be superimposed by chemically etching the surface under controlled conditions. Substrates will be designed that have comparable microarchitecture but different hydrophilicity. Cell culture models include: human osteoblast-like MG63 cells, normal human osteoblasts (NHOst cells), and the rat osteoblast-like cell line ROS 17/2.8. Three specific aims are proposed: Aim I. Examine the role of integrins in mediating the differential effects of surface design features on osteoblast phenotypic expression. Aim II. Examine the role of substrate architecture in the response of osteoblasts to 1,25(OH)2D3 and 17b- estradiol. Aim III. Examine the role of integrin-signaling in mediating the synergistic effect of surface design and steroid hormone action on osteoblast phenotypic expression. Thus, while our experiments are basic in nature, our intent is to conduct them in such a manner that the results can be applied to clinical implantology and tissue engineering.