膜科学与技术

聚-4-甲基-1-戊烯中空纤维氧合膜的研究进展与面临的挑战

作者：杜宇倩，邵丽萍，潘福生，张润楠，姜忠义

单位：天津大学化工学院，天津 300072

关键词：氧合膜；聚-4-甲基-1-戊烯；热致相分离法；血液相容性

出版年,卷(期):页码： 2021,41(3):169-178

摘要：

体外膜式氧合（ECMO）是一项生命支持技术，在心肺衰竭或心脏移植中发挥重要作用。氧合膜作为ECMO系统的核心部件之一，具有氧合血液和排出二氧化碳的功能。理想的氧合膜应具有高气体渗透性、良好的血液相容性、无血浆渗漏等特点，而聚-4-甲基-1-戊烯（PMP）由于其优异的气体渗透性成为氧合膜的首选材料。本文回顾了氧合膜的发展历程，综述了PMP中空纤维氧合膜的热致相制备技术和血液相容性改性技术（包括肝素化、两性离子聚合物改性和表面内皮化等），讨论了氧合膜面临的主要挑战及发展前景。

Extracorporeal membrane oxygenation (ECMO) is a life support method used to oxygenate blood and ventilate carbon dioxide, which plays an important role in the treatment of cardiopulmonary failure and lung transplantation. Membrane oxygenator is one of the core parts in ECMO. Poly-4-methyl-1-pentene (PMP) is an ideal membrane material for blood oxygenation which provides high gas permeability, good hemocompatability and less plasma leakage performance. This article reviews the development of oxygenated membrane, primarily focuses on the fabrication method of PMP hollow fiber membrane using thermally induced phase separation and surface modification technology to improve hemocompatibility with heparin, zwitterionic polymer and endothelial cells. Finally, the challenges and development prospects of membrane oxygenators are discussed.

杜宇倩（1996-），女，河南省周口市人，硕士研究生，研究方向为膜与膜过程；邵丽萍（1996-），女，河南省三门峡人，硕士研究生，研究方向为膜与膜过程

参考文献：

[1] Ventetuolo C E, Borchardt R, Brodie D. Mechanical Circulatory and Respiratory Support[M]//Academic Press, 2018: 245-269.
[2] 饶华新. 新型中空纤维膜式人工肺的设计与研究[D]. 暨南大学, 2008.
[3] Gibbon J H, Jr. Application of a mechanical heart and lung apparatus to cardiac surgery[J]. Minn Med, 1954, 37(3):171-passim.
[4] 杜明辉. 人工肺膜材料的生物相容性评价[J]. 中国组织工程研究与临床康复, 2009, 13(51):10137-10140.
[5] Melchior R W, Sutton S W, Harris W, et al. Evolution of membrane oxygenator technology for utilization during pediatric cardiopulmonary bypass[J]. Pediatric Health Med Ther, 2016, 7:45-56.
[6] Lim M W. The history of extracorporeal oxygenators[J]. Anaesthesia, 2006, 61(10):984-995.
[7] Evseev A K, Zhuravel S V, Alentiev A Y, et al. Membranes in Extracorporeal Blood Oxygenation Technology[J]. Membranes and Membrane Technologies, 2019, 1(4): 201-211.
[8] McCaughan J S, Weeder R, Schuder J C, et al. Evaluation of new nonwettable macroporous membranes with high permeability coefficients for possible use in a membrane oxygenator[J]. The Journal of Thoracic and Cardiovascular Surgery, 1960, 40(5): 574-581.
[9] Mueller M O, Kessler E, Hornscheidt R R, et al. Integrally asemmetrical polyolefin membrane for gas exchange[P]. US Pat, US6409921-B1. 2002-06-25.
[10] 段亚峰, 潘峰. 膜式氧合器用聚丙烯中空纤维膜超微结构[J]. 纺织学报, 2005, 26(3):29-32.
[11] 钱如勉. 塑料性能应用手册[M]//上海科学技术出版社, 1987: 66-69.
[12] Webster L. Biomaterials for Artificial Organs[M]//Woodhead Pub Ltd, 2011: 3-33.
[13] 王风婷, 罗峰. 膜式氧合器中膜材料的研究进展[J]. 中国组织工程研究与临床康复, 2008(10):1927-1930.
[14] Anazawa T, Ono Y. Heterogeneous membrane and process for production thereof[P]. US Pat, US4664681. 1985-11-01.
[15] Anazawa T, Murata K. Membrane-type artificial lung and method of using it[P]. EP Pat, EP99381-A2 1988-07-08
[16] Castro A J, Park O. Method for making microporous[P]. US Pat, US4247498. 1981-01-27.
[17] 计根良. 热致相分离法制备PVDF微孔膜的结构控制与性能研究[D]. 浙江大学, 2008.
[18] Lloyd D R, Kinzer K E, Tseng H S. Microporous membrane formation via thermally induced phase separation. I. Solid-liquid phase separation[J]. J Membr Sci, 1990, 52(3):239-261.
[19] Mueller M O, Kessler E, Hornscheidt R R, et al. Integrally asemmetrical polyolefin membrane for gas exchange[P]. US Pat, US6409921-B1. 2002-06-25.
[20] Erich K, Thomas B, Friedbert W, et al. Method for producing an integrally asymmetrical polyolefin membrane [P]. US Pat, US6375876 B1 2002-04-23.
[21] Kessler E, Batzilla T, Wechs F, et al. Integrally asymmetrical polyolefin membrane[P]. US Pat, US6497752-B1. 2002-12-24.
[22] Kessler E, Batzilla T, Wechs F, et al. Process for producing polyolefin membrane with integrally asymmetrical structure[P]. US Pat, US7429343 B2 2008-09-30.
[23] 罗本喆. 热致相分离法制备聚丙烯微孔膜的研究[D]. 南京工业大学, 2005.
[24] Tao H, Zhang J, Wang X. Effect of diluents on the crystallization behavior of poly(4-methyl-1-pentene) and membrane morphology via thermally induced phase separation[J]. J Appl Polym Sci, 2008, 108(2):1348-1355.
[25] Huang X, Wang W, Zheng Z, et al. Dissipative particle dynamics study and experimental verification on the pore morphologies and diffusivity of the poly (4-methyl-1-pentene)-diluent system via thermally induced phase separation: The effect of diluent and polymer concentration[J]. J Membr Sci, 2016, 514:487-500.
[26] Tang T, Xu M, Ling T, et al. Computer simulation and experimental verification of morphology and gas permeability of poly(4-methyl-1-pentene) membranes: effects of polymer chain and diluent extractant[J]. J Mater Sci, 2019, 54(15):10784-10797.
[27] 黄鑫. 热致相分离法制备聚4-甲基-1-戊烯中空纤维膜及其表面血液相容性改性[D]. 南京大学, 2016.
[28] Tao H J, Zhang J, Wang X L, et al. Phase separation and polymer crystallization in a poly(4-methyl-1-pentene)-dioctylsebacate-dimethylphthalate system via thermally induced phase separation[J]. J Polym Sci, Part B: Polym Phys, 2007, 45(2):153-161.
[29] Tao H, Xia Q, Chen S, et al. Solid-liquid phase separation of poly-4-methyl-1-pentene/diluent system via thermally induced phase separation[J]. Desalin Water Treat, 2010, 17(1-3):294-303.
[30] Zhang Q, Zhang Y, Xia D, et al. Preparation of a Porous Structure in a Poly(4-Methyl-1-Pentene)/Diphenyl Ether System with a Thermally Induced Phase-Separation Method[J]. J Appl Polym Sci, 2009, 112(3):1271-1277.
[31] Hedayati M, Neufeld M J, Reynolds M M, et al. The quest for blood-compatible materials: Recent advances and future technologies[J]. Mater Sci Eng R, 2019, 138:118-152.
[32] Michaljani?ová I, Slepi?ka P, Slepi?ková KasálkováN, et al. Plasma and laser treatment of PMP for biocompatibility improvement[J]. Vacuum, 2014, 107:184-190.
[33] Slepicka P, Trostova S, Kasalkova N S, et al. Nanostructuring of polymethylpentene by plasma and heat treatment for improved biocompatibility[J]. Polym Degrad Stab, 2012, 97(7):1075-1082.
[34] Huang X, Wang W P, Zheng Z, et al. Surface monofunctionalized polymethyl pentene hollow fiber membranes by plasma treatment and hemocompatibility modification for membrane oxygenators[J] Appl Surf Sci, 2016, 362:355-363.
[35] Ontaneda A, Annich G M. Novel Surfaces in Extracorporeal Membrane Oxygenation Circuits[J]. Front Med, 2018, 5:321-340.
[36] 李磊, 刘耀东, 黄鑫, 等. 一种低温等离子体改性膜式人工肺方法[P]. 中国专利, CN 104001224 A. 2014-08-27.
[37] 叶非华, 易国斌. 可交联磷酰胆碱聚合物改性聚甲基戊烯中空纤维膜[J]. 复合材料学报, 2021, 38.
[38] Malkin A D, Ye S H, Lee E J, et al. Development of zwitterionic sulfobetaine block copolymer conjugation strategies for reduced platelet deposition in respiratory assist devices[J]. J Biomed Mater Res, 2018, 106(7):2681-2692.
[39] Hess C, Wiegmann B, Maurer A N, et al. Reduced thrombocyte adhesion to endothelialized poly 4-methyl-1-pentene gas exchange membranes-a first step toward bioartificial lung development[J]. Tissue Eng, 2010, 16(10):3043-3053.
[40] Wiegmann B, Seggern H V, Hoffler K, et al. Developing a biohybrid lung - sufficient endothelialization of poly-4-methly-1-pentene gas exchange hollow-fiber membranes[J]. J Mech Behav Biomed Mater, 2016, 60:301-311.
[41] Pflaum M, Kuhn-Kauffeldt M, Schmeckebier S, et al. Endothelialization and characterization of titanium dioxide-coated gas-exchange membranes for application in the bioartificial lung[J]. Acta Biomater, 2017, 50:510-521.
[42] Cornelissen C G, Dietrich M, Gromann K, et al. Fibronectin coating of oxygenator membranes enhances endothelial cell attachment[J]. Biomed Eng, 2013, 12.
[43] Moller L, Hess C, Palecek J, et al. Towards a biocompatible artificial lung: Covalent functionalization of poly(4-methylpent-1-ene) (TPX) with cRGD pentapeptide[J]. Beilstein J Org Chem, 2013, 9:270-277.
[44] Pflaum M, Merhej H, Peredo A, et al. Hypothermic preservation of endothelialized gas-exchange membranes[J]. Artif Organs, 2020.
[45] Wiegmann B, Figueiredo C, Gras C, et al. Prevention of rejection of allogeneic endothelial cells in a biohybrid lung by silencing HLA-class I expression[J]. Biomaterials, 2014, 35(28):8123-8133.

服务与反馈：

【文章下载】【加入收藏】

《膜科学与技术》编辑部地址：北京市朝阳区北三环东路19号蓝星大厦邮政编码：100029 电话：010-64426130/64433466 传真：010-80485372邮箱：mkxyjs@163.com