APPLICATION OF BIOMATERIALS IMMOBILIZED WITH BIOSIGNAL MOLECULES

生物信号分子固定化生物材料的应用

• 批准号: 07505023
• 负责人: IMANISHI Yukio
• 金额: $ 9.02万
• 依托单位: NARA INSTITUTE OF SCIENCE AND TECHNOLOGY (1996-1997)Kyoto University (1995)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07505023/
• 关键词: BIOSIGNAL MOLECULE; GROWTH FACTOR; BIOMATERIAL; IMMOBILIZATION; ARTIFICIAL JUXTACRINE; EPIDERMAL GROWTH FACTOR; INSULIN; CELL ADHESION FACTOR; 神経細胞成長因子; 腫瘍壊死因子; 光リソグラフ; 無血清培養; 生体材料設計; EGF; 生体適合性; 細胞設計

Approaches for controlling the interface between tissue or cells and biomaterial can be divided into two categories. One is biolization of materials another chemical modification.Biolization invloves immobilization of anticoagulant or hybridization of blood endothelial cells for blood-compatibility, or immobilization of cell adhesive reptide for cell adhesives. In addition, immobilization of cell growth factor proteins enhances cell growth. The immobilization of biosignal proteins enables biomaterials to regulate various functions of cells, such as differentiation, secretion, and motility.Chemical modification involves surface hydrophilization or hydrophobilization, or electrochemical modification. Recent progress of polymer science has enabled space-time control of material surface. The position of cells can be regulated by photo-lithographic modification of the surface and the attachment and detachment of cells can be controlled by temperature manipulation of a thermo-sensitive polym … More er.Herein the surface was biolized for growth enhancement and differentiation promotion. In addition, space-time controlled intelligent biomaterials were achieved by the combination of biological and chemical approches. The intelligent biomaterials will be useful not only for medical applications but also for fundamental methodologies of biosensors and nano-biotechnology.Surface biolization was achieved by immobilization of cell growth factor proteins, insulin and epidermal growth factor (EGF). EGF is a membrane-bound growth factor which can stimulate cells without diffusion in medium by "juxtacrine stimulation". Immobilized insulin and EGF enhanced cell growth more than free insulinor EGF.In the culture of pheochromocytoma (PC12) cells, the immobilized EGF promoted neural differentiation but did not enhance the growth, although free EGF enhanced growth. The stimulation mode (juxtacrine and paracrine) switched the gene expression.Time-controlled intelligent biomaterial was prepared usinf thermo-sensitive polymer. By combination with insulin, the biomaterial enhanced cell growth and the grown cells were detached by lowering temperature.Spatial controlled biomaterial was achieved by pattern immobilization of thrermo-responsive polymer, insulin, and EGF.Selective detachment of growth cells was observed on the micro-patterned thermo-responsive polymer at a low temperature. Selective signal transduction was observed on th specific area immobilized with insulin or EGF.The technique was useful for visualization of juxtacrine stimulation by immobilized biosignals. Less

用于控制组织或细胞与生物材料之间的界面的方法可以分为两类。一种是材料的生物化，另一种是化学改性，生物化包括抗凝剂的固定化或血液内皮细胞的杂交以实现血液相容性，或细胞粘附肽的固定化以实现细胞粘附。此外，细胞生长因子蛋白质的固定化促进细胞生长。生物信号蛋白的固定化使生物材料能够调节细胞的分化、分泌、运动等多种功能，化学修饰包括表面疏水化、疏水化和电化学修饰。高分子科学的最新进展使材料表面的时空控制成为可能。细胞的位置可以通过光刻修饰表面来调节，细胞的附着和脱离可以通过温度控制热敏聚合物来控制。 ...更多信息 在此，将表面生物化以促进生长和分化。此外，通过生物和化学方法的结合，实现了时空可控的智能生物材料。智能生物材料不仅在医学上有重要的应用，而且在生物传感器和纳米生物技术的基础研究中也有重要的应用。EGF是一种膜结合的生长因子，它可以通过“阿曲他克林刺激”刺激细胞而不在培养基中扩散。在培养的PC12细胞中，固定化EGF促进神经分化，但不促进生长，而游离EGF促进生长。利用温敏性高分子材料制备了时控智能生物材料。通过与胰岛素的结合，促进了细胞的生长，并通过降低温度使生长的细胞脱离，通过图案化固定胰岛素、EGF和热响应聚合物，实现了空间可控的生物材料，在低温下观察到生长细胞在微图案化热响应聚合物上的选择性脱离。在固定有胰岛素或EGF的特定区域观察到选择性的信号转导，该技术可用于固定生物信号对阿曲他克林刺激的可视化。少

项目成果

Y.Ito, S.kondo, G.Chen, Y.Imanishi: "Patterned artificial juxtacrine stimulation of cells by covalently immobilized insulin" FEBS Lett.403. 159-162 (1997)

Y.Ito、S.kondo、G.Chen、Y.Imanishi：“通过共价固定胰岛素对细胞进行图案化人工近分泌刺激”FEBS Lett.403。

Y.Ito, J.Zheng, Y.Imaishi: "Enhancement of cell growth on a porous membrane co-immobilized with cell-growth and cell-adhesion factors" Biomaterials. 18. 197-202 (1997)

Y.Ito、J.Zheng、Y.Imaishi：“在与细胞生长和细胞粘附因子共同固定的多孔膜上增强细胞生长”生物材料。

Y.Ito, J.-S.Li, T.Takahashi, Y.Imanishi, Y.Okabayashi, M.Kosuge: "Enhancement of mitogenic effect by artificial juxtacrino stimulation using immobilized EGF" J.Biochem.121. 514-520 (1997)

Y.Ito、J.-S.Li、T.Takahashi、Y.Imanishi、Y.Okabayashi、M.Kosuge：“使用固定化 EGF 人工 Juxtacrino 刺激增强有丝分裂作用”J.Biochem.121。

今西幸男: "Polymaric Materials Encyclopedia" CRC Press(Boca Raton USA), 9,600 (1996)

今西幸雄：《高分子材料百科全书》CRC Press（美国博卡拉顿），9,600 (1996)

J.-S.Li, Y.Ito J.Zheng, T.Takahashi, Y.Imanishi: "Enhancement of artificial juxtacrine stimulation of insulin by coimmobilization wity adhesion foctors" J.Biomed.Meter.Res. 31. 190-197 (1997)

J.-S.Li、Y.Ito J.Zheng、T.Takahashi、Y.Imanishi：“通过粘附因子共固定增强胰岛素的人工近分泌刺激”J.Biomed.Meter.Res。