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The Roles of Membrane Technology in Artificial Organs membranes Review The Roles of Membrane Technology in Artificial Organs: Current Challenges and Perspectives Bao Tran Duy Nguyen 1 , Hai Yen Nguyen Thi 1, Bich Phuong Nguyen Thi 1, Dong-Ku Kang 2,* and Jeong F. Kim 1,3,* 1 Department of Energy and Chemical Engineering, Incheon National University, Incheon 22012, Korea; bao.nguyen@inu.ac.kr (B.T.D.N.); haiyen0107@inu.ac.kr (H.Y.N.T.); 202022027@inu.ac.kr (B.P.N.T.) 2 Department of Chemistry, Incheon National University, Incheon 22012, Korea 3 Innovation Center for Chemical Engineering, Incheon National University, Incheon 22012, Korea * Correspondence: dkkang@inu.ac.kr (D.-K.K.); JeongKim@inu.ac.kr (J.F.K.) Abstract: The recent outbreak of the COVID-19 pandemic in 2020 reasserted the necessity of artificial lung membrane technology to treat patients with acute lung failure. In addition, the aging world population inevitably leads to higher demand for better artificial organ (AO) devices. Membrane technology is the central component in many of the AO devices including lung, kidney, liver and pancreas. Although AO technology has improved significantly in the past few decades, the quality of life of organ failure patients is still poor and the technology must be improved further. Most of the current AO literature focuses on the treatment and the clinical use of AO, while the research on the membrane development aspect of AO is relatively scarce. One of the speculated reasons is the wide interdisciplinary spectrum of AO technology, ranging from biotechnology to polymer chemistry and process engineering. In this review, in order to facilitate the membrane aspects of the Citation: Duy Nguyen, B.T.; Nguyen AO research, the roles of membrane technology in the AO devices, along with the current challenges, Thi, H.Y.; Nguyen Thi, B.P.; Kang, are summarized. This review shows that there is a clear need for better membranes in terms of D.-K.; Kim, J.F. The Roles of biocompatibility, permselectivity, module design, and process configuration. Membrane Technology in Artificial Organs: Current Challenges and Keywords: membrane; artificial organs; artificial kidney; artificial lung; artificial liver; bioartificial Perspectives. Membranes 2021, 11, 239. pancreas; biocompatibility https://doi.org/10.3390/ membranes11040239 Academic Editor: Jong Suk Lee 1. Introduction Every living organism strives to maintain homeostasis with the surrounding environ- Received: 1 March 2021 ments. The cells, tissues, and organs of a living organism control its internal environments Accepted: 20 March 2021 Published: 28 March 2021 to maintain safe concentration ranges in order to maintain life. In cases of unexpected tissue damage or organ failures, cells have an extraordinary ability to repair themselves Publisher’s Note: MDPI stays neutral and to regain homeostasis. However, some acute and chronic damages can be irreversible, with regard to jurisdictional claims in leading to life-threatening failures that require medical intervention and treatment. published maps and institutional affil- The median age of the world population has increased steadily (Figure1). Such an iations. aging population inevitably leads to higher chances of organ failures, and the best available treatment for such patients now is organ transplantation. However, as shown in Figure1, the gap between the number of organ donors and the number of patients has expanded steadily and is only expected to get wider. In addition, although the stem-cell-derived treatment could be a promising option in the future [1–4], it has not been fully developed Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. yet. Hence, currently, the optimal solution for organ failure patients in the short-term is This article is an open access article artificial organ (AO) technology, until the patient recovers (i.e., bridge-to-recovery) or until distributed under the terms and the patient receives an organ transplant (i.e., bridge-to-transplantation). conditions of the Creative Commons The advancements in AO technology are truly astonishing, and they are increasingly Attribution (CC BY) license (https:// becoming important, even necessary, in the modern medical treatments. Nowadays, creativecommons.org/licenses/by/ AO technology can partly augment the functions of the human organs by maintaining 4.0/). physiochemical gradients in the safe range. Many of these AOs employ synthetic polymeric Membranes 2021, 11, 239. https://doi.org/10.3390/membranes11040239 https://www.mdpi.com/journal/membranes Membranes 2021, 11, 239 2 of 33 Membranes 2021, 11, x FOR PEER REVIEWmembranes to assist the physical and chemical functions of the failed organs. Particularly,2 of 35 AOs that employ membrane technology includes artificial lung, kidney, liver, and pancreas. Figure 1. NumberNumber of of people people receiving receiving transplants, transplants, wait waitinging for for transplants, transplants, and and donors donors in inthe the USUS (data obtained from [[5]),5]), plottedplotted togethertogether withwith thethe statisticstatistic ofof thethe WorldWorld MedianMedian AgeAge (data(data obtainedob- tainedfrom [6 from]). [6]). TheMembrane advancements technology in AO has technology also made are incredible truly astonishing, strides inand the they past are few increasingly decades. becomingNotably, water important, purification even necessary, and desalination in the modern membranes medical have treatments. reached the Nowadays, state-of-the-art, AO technologydominating can more partly than augment half of the the desalination functions marketof the human [7]. Ion organs exchange by membranesmaintaining such physi- as ochemicalNafion have gradients become ain main the safe component range. Many for fuel of cell these technology. AOs employ Moreover, synthetic gas separationpolymeric membranes to are assist now the a key physical player and in chemical many fields functions including of the CO failed2 capture organs. and Particularly, hydrogen purificationAOs that employ [8]. As membrane a separate front,technology membranes includ fores theartificial healthcare lung, andkidney, biomedical liver, and markets, pan- whichcreas. are the main topic of this review, have steadily increased their market share [9]. MembraneThe market technology size of the artificialhas also kidneymade incredible (e.g., hemodialysis) strides in the reached past few USD decades. 74 billion No- in tably,2019 [ 10water]. As purification for the artificial and lung desalination market, also me commonlymbranes have known reached as ECMO the state-of-the-art, (extracorporeal dominatingmembrane oxygenator), more than half is expected of the desalinati to growon up market to USD [7]. 305 Ion million exchange by 2021 membranes [11]. However, such asthis Nafion forecast have may become have changed a main component with the recent for fuel outbreak cell technology. of COVID-19 Moreover, in 2020, asgas ECMO separa- is tionone ofmembranes the key treatments are now afor key severe player COVID-19 in many fields patients. including The artificial CO2 capture liver and and hydrogen pancreas purificationmarkets are still[8]. relativelyAs a separate small front, because memb theranes technology for the is healthcare not mature and enough biomedical and is as mar- yet withoutkets, which firm are clinical the main effectiveness topic of this data. review, have steadily increased their market share [9]. Surprisingly, despite the considerable market size of the healthcare industries, the literatureThe market on membrane size of the research artificial in kidney such fields (e.g., is hemodialysis) relatively scarce reached compared USD 74 to otherbillion ap- in plications2019 [10]. As such for as the water artificial and gaslung separation market, also membranes. commonly In known fact, there as ECMO is a large (extra amountcorpo- realof literature membrane that oxygenator), reports the useis expected of AO for to grow clinical up research, to USD 305 but million not as manyby 2021 that [11]. actually How- ever,develop this AO forecast membranes. may have One changed of the reasons with th maye recent be that outbreak AO research of COVID-19 requires in interdisci- 2020, as plinaryECMO is knowledge one of the and key there treatments exists a for wide severe gap betweenCOVID-19 the patients. membrane The field artificial and biomedical liver and pancreastechnology. markets Membrane are still researchers relatively are small primarily because from the the technology nonbiomedical is not disciplines,mature enough and viceand is versa. as yet without firm clinical effectiveness data. Surprisingly,Although the artificialdespite the kidney considerable technology market can be size considered of the healthcare as mature clinically,industries, other the literaturetypes of membrane-based on membrane research AOs, such in such as artificial fields is lung, relatively liver, andscarce pancreas, compared still to suffer other from ap- plicationsmany technical such as challenges water and that gas must separation be resolved membranes. urgently. In Needless fact, there to say,is a large such challengesamount of literatureare very complex, that reports requiring the use interdisciplinary of AO for clinical collaboration research, but across not theas many fields ofthat chemistry, actually developbiology, materials,AO membranes. and engineering. One of the In reasons addition, may the be quality that AO of research life of organ requires failure interdisci- patients, albeit improved, is still poor. The AO technology must continuously improve not
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