Amemiya Ryusuke, Shinoda Masahiro, Yamada Masayuki, Ueno Yoshiyuki, Shimada Kaoru, Fujieda Hiroaki, Yagi Hiroshi, Mizota Takamasa, Nishiyama Ryo, Oshima Go, Yamada Shingo, Matsubara Kentaro, Abe Yuta, Hibi Taizo, Kitago Minoru, Obara Hideaki, Itano Osamu, Kitagawa Yuko
1 Department of Surgery, Keio University School of Medicine, Tokyo, Japan.
2 Medical Devices & Materials Research Unit, Advanced Materials Research Laboratories, Toray Industries, Inc., Shiga, Japan.
Int J Artif Organs. 2018 Apr;41(4):190-200. doi: 10.1177/0391398817752296. Epub 2018 Mar 11.
High-mobility-group box chromosomal protein 1 has been identified as an important mediator of various kinds of acute and chronic inflammation. In this study, we aimed to develop a column that effectively adsorbs high-mobility-group box chromosomal protein 1 by altering the pore size of the fiber.
First, we produced three types of porous polymethylmethacrylate fiber by altering the concentration of polymethylmethacrylate dissolved in dimethylsulfoxide. We then selected a fiber based on the results of an in vitro incubation test of high-mobility-group box chromosomal protein 1 adsorption. Using the selected fiber, we constructed a new column and tested its high-mobility-group box chromosomal protein 1 adsorption capacity during 4-h extracorporeal hemoperfusion in a swine acute liver failure model.
Electron microscope observation showed that the three types of fibers had different pore sizes on the surface and in cross section, which were dependent on the concentration of polymethylmethacrylate. In the in vitro incubation test, fiber with moderate-sized pores demonstrated the highest adsorption capacity. In the in vivo hemoperfusion study, the ratio of the high-mobility-group box chromosomal protein 1 concentration at the outlet versus the inlet of the column was significantly lower with the new column than with the control column during 4-h extracorporeal hemoperfusion. The normalized plasma level of high-mobility-group box chromosomal protein 1 at 12 h after the completion of hemoperfusion was significantly lower with the new column than with the control column.
The newly developed polymethylmethacrylate column adsorbs high-mobility-group box chromosomal protein 1 during hemoperfusion in swine ALF model.
高迁移率族蛋白B1已被确定为各种急慢性炎症的重要介质。在本研究中,我们旨在通过改变纤维的孔径来开发一种能有效吸附高迁移率族蛋白B1的柱体。
首先,我们通过改变溶解在二甲基亚砜中的聚甲基丙烯酸甲酯的浓度制备了三种类型的多孔聚甲基丙烯酸甲酯纤维。然后,根据高迁移率族蛋白B1吸附的体外孵育试验结果选择一种纤维。使用所选纤维,我们构建了一个新的柱体,并在猪急性肝衰竭模型的4小时体外血液灌流过程中测试其高迁移率族蛋白B1吸附能力。
电子显微镜观察显示,三种类型的纤维在表面和横截面上具有不同的孔径,这取决于聚甲基丙烯酸甲酯的浓度。在体外孵育试验中,具有中等孔径的纤维表现出最高的吸附能力。在体内血液灌流研究中,在4小时体外血液灌流期间,新柱体柱出口处与入口处的高迁移率族蛋白B1浓度之比显著低于对照柱体。血液灌流完成后12小时,新柱体柱的高迁移率族蛋白B1标准化血浆水平显著低于对照柱体。
新开发的聚甲基丙烯酸甲酯柱体在猪急性肝衰竭模型的血液灌流过程中吸附高迁移率族蛋白B1。