Ho Ye Sang, Watanabe Junji, Takai Madoka, Iwasaki Yasuhiko, Ishihara Kazuhiko
Department of Materials Engineering, School of Engineering, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
Biomaterials. 2006 Mar;27(9):1955-62. doi: 10.1016/j.biomaterials.2005.09.041. Epub 2005 Oct 18.
For practical application of a liver assist system with a tissue-conjugated hollow fiber membrane (HFM) bioreactor used in an extracorporeal therapy, it would require a highly sophisticated HFM which has both hemocompatibility on one side and cytocompatibility on the other side. In this study, we present a cellulose acetate (CA) HFM modified with 2-methacryloyloxyethyl phosphorylcholine (MPC) copolymers (PMB30 (MPC-co-n-butyl methacrylate) and PMA30 (MPC-co-methacrylic acid) for preparing a novel liver assist HFM bioreactor. A CA/PMB-PMA30 HFM modified asymmetrically on the inner and outer surface with the PMB30 and PMA30 was prepared successfully. Analysis with an X-ray photoelectron spectroscope showed that the intensity of the phosphorus atom attributed to the MPC units on the outer surface of the modified HFM was stronger than that of the inner surface. The PMA30 was immobilized on the outer surface of the CA/PMB30 blend HFM by a chemical condensation reaction. The CA/PMB-PMA30 HFM showed good water and solute permeability in comparison with the CA HFM. The morphologies of the adherent hepatocytes were round in shape in comparison with the cells that adhered on CA HFM. Furthermore, hepatocytes cultured on the inner surface of the CA/PMB-PMA30 HFM showed higher functional expression in terms of urea synthesis and albumin synthesis than that of the CA HFM.
对于用于体外治疗的带有组织共轭中空纤维膜(HFM)生物反应器的肝辅助系统的实际应用,需要一种高度复杂的HFM,其一侧具有血液相容性,另一侧具有细胞相容性。在本研究中,我们展示了一种用2-甲基丙烯酰氧基乙基磷酰胆碱(MPC)共聚物(PMB30(MPC-共-甲基丙烯酸正丁酯)和PMA30(MPC-共-甲基丙烯酸)改性的醋酸纤维素(CA)HFM,用于制备新型肝辅助HFM生物反应器。成功制备了一种在内外表面不对称地用PMB30和PMA30改性的CA/PMB-PMA30 HFM。用X射线光电子能谱仪分析表明,改性HFM外表面上归因于MPC单元的磷原子强度比内表面强。通过化学缩合反应将PMA30固定在CA/PMB30共混HFM的外表面。与CA HFM相比,CA/PMB-PMA30 HFM表现出良好的水和溶质渗透性。与粘附在CA HFM上的细胞相比,粘附的肝细胞形态呈圆形。此外,在CA/PMB-PMA30 HFM内表面培养的肝细胞在尿素合成和白蛋白合成方面表现出比CA HFM更高的功能表达。