Mechanisms of Cell / Surface Interaction

描述(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做出反应的机制，以便改善临床使用的设备和组合产品的功能。使用钛(钛)底物的研究表明，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，而不需要药物修饰。本提案的目的是使用结构化材料表面来定义微米级和亚微米级的地形特征来调节特定的细胞反应，并了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，促进正常组织的再生和修复。我们的实验假设是，表面的物理和化学性质决定了整合素的表达，影响细胞信号和对调控成骨的因素的反应，如1，25-二羟基维生素D3[1，25(OH)2D3]和雌激素。我们将检验成骨细胞在特定的钛表面上的行为，这些钛表面通过电化学微加工来产生微米级的结构特征；亚微米级的地形将通过在受控条件下对表面进行化学腐蚀来叠加。基质的设计将具有类似的微结构，但亲水性不同。细胞培养模型包括：人成骨样MG63细胞、正常人成骨细胞(NHOst细胞)和大鼠成骨样细胞系ROS17/2.8。提出了三个具体的目标：目的1.研究整合素在调节表面设计特征对成骨细胞表型表达的不同影响中的作用。目的II.研究底物构型在成骨细胞对1，25(OH)2D3和17b-雌二醇反应中的作用。目的III.研究整合素信号在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，虽然我们的实验本质上是基础的，但我们的目的是以一种可以将结果应用于临床植入学和组织工程学的方式进行实验。

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.