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乳糖酸功能化聚醚砜中空纤维膜促进HepG2细胞附着及功能。

Lactobionic acid-functionalized polyethersulfone hollow fiber membranes promote HepG2 attachment and function.

作者信息

Verma Surendra Kumar, Modi Akshay, Dravid Ashwin, Bellare Jayesh

机构信息

Department of Chemical Engineering, Indian Institute of Technology Bombay Mumbai 400076 India

Centre for Research in Nanotechnology & Sciences, Indian Institute of Technology Bombay Mumbai 400076 India.

出版信息

RSC Adv. 2018 Aug 14;8(51):29078-29088. doi: 10.1039/c8ra02282h.

Abstract

Surface modification of polyethersulfone hollow fibers, which are important in bio-artificial liver, is increasingly used to improve biocompatibility and promote the adhesion and proliferation of hepatocytes resulting in improved cell functionality. Hepatocytes are anchorage-dependent cells, and membrane surface modification enhances the hepatic cell adhesion and proliferation. Specific interaction of the asialoglycoprotein receptor on hepatocyte cell surfaces with a galactose moiety enhances the attachment of the cells on a biocompatible substrate. In this study, the outer surface of the polyethersulfone (P) hollow fiber membranes (HFMs) was chemically modified by covalent coupling with lactobionic acid (LBA). The energy dispersive X-ray spectrometry elemental mapping, attenuated total reflectance-Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy confirmed the LBA-coupling on the outer surface of P-LBA HFMs. Hemocompatibility study indicated the suitability of the modified membranes with human blood. These membranes showed remarkably improved biocompatibility with human primary mesenchymal stem cells and HepG2 cells. Characteristic multi-cellular spheroids of HepG2 cells were observed under scanning electron and confocal microscopy. HepG2 cell functional activity was measured by quantifying the urea synthesis, albumin secretion and glucose consumption in the culture media, which indicated the improved HepG2 functions. These experimental results clearly suggest the potentiality of these LBA-modified P HFMs as a suitable biocompatible substrate for promoting HepG2 attachment and function leading to their application in bioreactors and bio-artificial liver devices.

摘要

聚醚砜中空纤维的表面改性在生物人工肝中具有重要意义,其越来越多地用于改善生物相容性并促进肝细胞的黏附与增殖,从而提高细胞功能。肝细胞是锚定依赖性细胞,膜表面改性可增强肝细胞的黏附与增殖。肝细胞表面的去唾液酸糖蛋白受体与半乳糖部分的特异性相互作用可增强细胞在生物相容性基质上的附着。在本研究中,聚醚砜(P)中空纤维膜(HFMs)的外表面通过与乳糖酸(LBA)共价偶联进行化学改性。能量色散X射线光谱元素映射、衰减全反射傅里叶变换红外光谱和X射线光电子能谱证实了LBA在P-LBA HFMs外表面的偶联。血液相容性研究表明改性膜对人血的适用性。这些膜与人类原代间充质干细胞和HepG2细胞表现出显著改善的生物相容性。在扫描电子显微镜和共聚焦显微镜下观察到了HepG2细胞特征性的多细胞球体。通过定量培养基中的尿素合成、白蛋白分泌和葡萄糖消耗来测量HepG2细胞的功能活性,这表明HepG2功能得到了改善。这些实验结果清楚地表明,这些LBA改性的P HFMs作为促进HepG2附着和功能的合适生物相容性基质具有潜力,可应用于生物反应器和生物人工肝装置。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a565/9084356/9a600504e2d6/c8ra02282h-f1.jpg

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