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用于生物医学应用的含RGD肽丙烯酸三元共聚物的合成与表征

Synthesis and characterization of acrylic terpolymers with RGD peptides for biomedical applications.

作者信息

Fussell Garland W, Cooper Stuart L

机构信息

Department of Chemical Engineering, University of Delaware, Newark, DE 19716, USA.

出版信息

Biomaterials. 2004 Jul;25(15):2971-8. doi: 10.1016/j.biomaterials.2003.09.062.

Abstract

The goal of this research was to design a biomaterial, using acrylic terpolymers, which could support endothelial cells and function in small diameter vascular graft applications. Hexyl methacrylate (HMA) and octyl methacrylate (OMA) were used as comonomers to produce a material with a low glass transition temperature (T(g)). Methacrylic acid (MAA) was used to provide ionic character, and methyl methacrylate (MMA) was selected because of its wide usage in biomedical applications. Cation neutralization was employed to modify the mechanical properties. RGD-based peptide sequences were attached to promote endothelial cell adhesion, because vascular grafts seeded with endothelial cells have fewer problems with thrombosis. The two methods used to incorporate peptide sequences were a chain transfer reaction during polymerization, and a coupling reaction attaching the peptides to carboxyl groups on the polymer after polymerization. The compositions that produced T(g)s of approximately 0 degrees C were 75 mol% OMA and 92 mol% HMA. The Young's modulus of the HMA copolymer was approximately 0.37 MPa, well below the desired value of 0.9 MPa. Likewise, the Young's modulus of approximately 0.50 MPa for the OMA copolymer was also below the desired value. After partial neutralization with sodium cations, the Young's moduli increased to approximately 0.93 and 0.99 MPa, respectively. The chain transfer reaction lowered the molecular weights and mechanical properties of the copolymers, while the coupling reaction method had little effect on these properties. The chain transfer method appears to be a promising one-step method to produce polymers with a wide range of peptide concentrations.

摘要

本研究的目标是设计一种使用丙烯酸三元共聚物的生物材料,该材料能够支持内皮细胞,并在小直径血管移植物应用中发挥作用。甲基丙烯酸己酯(HMA)和甲基丙烯酸辛酯(OMA)用作共聚单体以生产具有低玻璃化转变温度(T(g))的材料。甲基丙烯酸(MAA)用于提供离子特性,而甲基丙烯酸甲酯(MMA)因其在生物医学应用中的广泛使用而被选用。采用阳离子中和来改变机械性能。连接基于RGD的肽序列以促进内皮细胞粘附,因为接种了内皮细胞的血管移植物在血栓形成方面问题较少。用于引入肽序列的两种方法是聚合过程中的链转移反应,以及聚合后将肽连接到聚合物上羧基的偶联反应。产生约0℃ T(g)的组合物为75摩尔% OMA和92摩尔% HMA。HMA共聚物的杨氏模量约为0.37 MPa,远低于所需的0.9 MPa值。同样,OMA共聚物约0.50 MPa的杨氏模量也低于所需值。用钠离子部分中和后,杨氏模量分别增加到约0.93和0.99 MPa。链转移反应降低了共聚物的分子量和机械性能,而偶联反应方法对这些性能影响不大。链转移方法似乎是一种有前景的一步法,可用于生产具有广泛肽浓度的聚合物。

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