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Synthesis and characterization of acrylic copolymers with RGD peptide to promote endothelial cell adhesion.

机译:具有RGD肽的丙烯酸共聚物的合成和表征,可促进内皮细胞粘附。

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The goal of this research was to design a biomaterial, using acrylic copolymers, which could support endothelial cells and function in small diameter vascular grafts, with fewer thrombosis problems than typical materials. Hexyl methacrylate (HMA) and octyl methacrylate (OMA) were used as comonomers to produce a material with a low glass transition temperature (Tg), so the material would be flexible. Methacrylic acid (MAA) provided ionic character to the copolymer, and methyl methacrylate (MMA) was selected because of its usage in other biomedical applications. Neutralization with sodium was employed to modify the mechanical properties. RGD peptides were attached to the copolymers to promote endothelial cell adhesion. Two methods were used to incorporate the peptide sequences. The first method explored the ability of peptide sequences to attach to a copolymer via chain transfer. The second method coupled the amine terminus of the peptides to the carboxyl groups in the copolymer. Human umbilical vein endothelial cell (HUVEC) adhesion to the copolymers was studied using confocal and optical microscopy.; The copolymer compositions that produced Tgs of approximately 0°C were 75 mol% OMA and 92 mol% HMA. The Young's moduli of the copolymers with 75 mol% OMA and 92 mol% HMA were approximately 0.50 and 0.37 MPa, respectively. These were below the desired value of 0.9 MPa. After partially neutralizing the HMA and OMA based copolymers with sodium cations, the Young's moduli increased to approximately 0.93 MPa and 0.99 MPa, respectively. The chain transfer method of peptide incorporation lowered the molecular weights and mechanical properties, while the coupling reaction method had little effect. The peptide concentrations for the chain transfer method of peptide incorporation ranged from 0.17 × 10−5 to 0.70 × 10−5 moles of peptide per gram of copolymer, compared with 0.83 × 10−5 and 8.1 × 10−5 moles/g for the coupling reaction method. Endothelial cell adhesion was not greatly affected by the method of peptide incorporation. As the peptide concentration increased, the number of cells adherent increased, up to a peptide concentration of approximately 0.50 × 10−5 moles/g. This indicates that endothelial cells achieve maximal adhesion at this peptide concentration.
机译:这项研究的目的是设计一种使用丙烯酸共聚物的生物材料,该材料可以支持内皮细胞并在小直径的血管移植物中发挥作用,与常规材料相比,具有更少的血栓形成问题。甲基丙烯酸己酯(HMA)和甲基丙烯酸辛酯(OMA)被用作共聚单体,以生产具有低玻璃化转变温度(T )的材料,因此该材料具有柔韧性。甲基丙烯酸(MAA)为共聚物提供了离子特性,而选择甲基丙烯酸甲酯(MMA)是因为它在其他生物医学应用中的用途。用钠中和以改变机械性能。 RGD肽连接到共聚物,以促进内皮细胞粘附。使用两种方法来整合肽序列。第一种方法探讨了肽序列通过链转移连接到共聚物上的能力。第二种方法将肽的胺末端与共聚物中的羧基偶联。使用共聚焦和光学显微镜研究了人脐静脉内皮细胞(HUVEC)对共聚物的粘附性。产生约0℃的Tg的共聚物组合物为75摩尔%的OMA和92摩尔%的HMA。具有75mol%的OMA和92mol%的HMA的共聚物的杨氏模量分别为约0.50和0.37MPa。它们低于0.9MPa的期望值。在用钠阳离子部分中和基于HMA和OMA的共聚物后,杨氏模量分别增加到大约0.93 MPa和0.99 MPa。引入肽的链转移方法降低了分子量和机械性能,而偶联反应方法几乎没有效果。肽掺入链转移法的肽浓度范围为每克共聚物0.17×10 -5 至0.70×10 -5 摩尔,而0.83×偶联反应方法为10 −5 和8.1×10 −5 摩尔/ g。肽掺入方法对内皮细胞的粘附影响不大。随着肽浓度的增加,粘附的细胞数量增加,直至肽浓度约为0.50×10 -5 / g。这表明在该肽浓度下内皮细胞达到最大粘附。

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