Mechanisms of Cell / Surface Interaction

细胞/表面相互作用的机制

• 批准号: 7847183
• 负责人: Barbara D. Boyan
• 金额: $ 0.94万
• 依托单位: GEORGIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-10 至 2009-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7847183
• 关键词: 17p; Ablation; Acids; Address; Agonist; Alkaline Phosphatase; Antibodies; Architecture; Behavior; Biomimetics; Blast Cell; Cell Count; Cell Culture Techniques; Cell Line; Cell surface; Cells; Chemicals; Chemistry; Clinical; Complex; Conjugated Estrogens; Data; Devices; Dinoprostone; Disease; Dose; Enzymes; Estradiol; Estrogen Receptors; Estrogens; Exhibits; Extracellular Matrix; Goals; Growth Factor; Habitats; Hormones; Human; Immunoassay; Implant; In Vitro; Integrin Binding; Integrin Signaling Pathway; Integrins; Marrow; Measures; Mediating; Membrane; Modeling; Modification; Morphology; Nature; Normal Cell; Normal tissue morphology; Nuclear; Nuclear Receptors; Osteoblasts; Osteocalcin; Osteoclasts; Osteogenesis; Pathway interactions; Patients; Peptides; Physiology; Plastics; Polishes; Process; Production; Prostaglandins; Protocols documentation; RGD (sequence); Rattus; Relative (related person); Role; Signal Pathway; Signal Transduction; Small Interfering RNA; Structure; Surface; Testing; Time; Tissue Engineering; Tissues; Titanium; Variant; bone; calreticulin; cell attachment protein; cell behavior; chemical property; conditioning; cyclooxygenase 1; cytokine; design; dihydroxy-vitamin D3; hydrophilicity; implant material; improved functioning; in vivo; inhibiting antibody; osteopontin; overexpression; prevent; receptor; repaired; research study; response; sex; steroid hormone; submicron; tissue culture; tissue regeneration

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.

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响应植入材料的机制，以改善临床使用的设备和组合产品的功能。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传导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的地形特征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，促进正常组织再生和修复。我们的实验假设是，表面的物理和化学特性决定了整合素的表达，影响细胞信号传导和对调节成骨因子（例如 1,25-二羟基维生素 D3 [1,25(OH)2D3] 和雌激素）的反应。我们将检查使用电化学微机械加工制备的限定钛表面上的成骨细胞行为，以产生微米级结构特征；亚微米尺度的形貌将通过在受控条件下对表面进行化学蚀刻来叠加。基材将被设计为具有类似的微结构但不同的亲水性。细胞培养模型包括：人成骨细胞样MG63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： 目标 I. 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影响中的作用。目标二。检查底物结构在成骨细胞对 1,25(OH)2D3 和 17b-雌二醇的反应中的作用。目标三。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，虽然我们的实验本质上是基础性的，但我们的目的是以这样的方式进行这些实验，使得结果可以应用于临床种植学和组织工程。