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JOURNAL OF MEMBRANE SCIENCE · 2019 · IF 7.015

Heparin reduced dialysis through a facile anti-coagulant coating on flat and hollow fiber membranes

Yang Liu,Qiu Han,Tiantain Li,Jing Hua,Fu Liu,Qiang Li,Gang Deng

Heparin free prescription is highly desired for haemodialysis. Versatile strategies have been developed to address the anti-coagulation modification of dialysis membranes. We here develop a facile and effective method to construct an anticoagulant coating on polymeric membranes or a dialyzer through hydrophobic-hydrophobic interaction. An amphiphilic heparin-like copolymer was first synthesized via a free radical polymerization based on alkyl chain lauryl methacrylate (LMA), acrylic acid (AA), and sodium 4-vinylbenze-sulfonate (SSNa) segments. The specific structure of terpolymer was characterized via Fourier transform infrared spectra (FTIR), Proton nuclear magnetic resonance ( 1 H NMR) spectra and size exclusion chromatography (SEC). The amphiphilic copolymer was anchored onto Polylactide (PLA) membrane surface from an aqueous-based solution via hydrophobic-hydrophobic interaction. An Attenuated total reflectance Fourier transform infrared spectra (ATR-FTIR), energy dispersive spectrometer (EDS) and X-ray photoelectron spectroscopy (XPS) confirmed the successful immobilization of heparin-mimicking terpolymers. The modified membranes showed excellent antifouling property and hydrophilicity. Moreover, the membranes exhibited outstanding haemocompatibility with suppressed platelet adhesion, low complement activation (C3a and C5a), expanded coagulation time and limited haemolysis ratio. The prolonged activated partial thromboplastin time and thrombin time (APTT>600 s, TT > 140 s) certified the excellent self-anticoagulant performances. To further examine the applicability and effectiveness, a polysulfone dialyzer was modified by this strategy. The ultrafiltration coefficient and clearance performances were examined. Overall, the hydrophobic-hydrophobic interaction strategy simplified the modification procedure of dialysis membrane, implying its great potential in heparin free dialysis application.

研究领域: 生物医学工程 · 材料科学 · 血液净化技术
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Science of Advanced Materials · 2020 ·Vol. 12 ·期 12 ·1896-1906 · IF 1.117

Preparation of Composite Polymer Biofilm Material and Its Adoption in Hemodialysis

Che Lishuang,Chen Jinhai,Zhang Yun,Li Yuangen,Li Yueting

In this study, cellulose is used as the raw material. Considering that polyether sulfone has good biocompatibility and can reduce protein adsorption, the ionic liquid is used to dissolve, and dry-wet phase conversion method is used to blend cellulose and polyether sulfone to produce the composite polymer hemodialysis membrane material. Then, an anticoagulant/hydrophilic heparinoid is synthesized and applied to the dialyzer made of composite polymer dialysis membrane material. During the preparation process, the spinning solution (SS) temperature, air gap (AG) length, and coagulation bath (CB) temperature are changed, and their effects on the structure/performance of the dialysis membrane are analyzed. The test shows that the spinning liquid temperature shouldn’t exceed 100 °C, the AG length shouldn’t exceed 10.0 cm, and the CB temperature at 30.6 °C could maximize the performance of the dialysis membrane. In the experiment, the new heparin is divided into three structural systems (M-1, M-3, M-1 / M-2), which are applied to the dialysis membrane to obtain three kinds of dialysis membrane (CP-A, CP-B, CP-C). The hydrophilic groups on the surface of the composite polymer dialysis membrane are modified to form a hydration layer with water to avoid direct contact between proteins and the polymer dialysis membrane, and APTT test value reaches 600 s, which proves that the dialyzer designed with dialysis membrane material in this study has a good anticoagulation effect.

研究领域: 生物材料学 · 医学工程 · 生物医学
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JOURNAL OF MEMBRANE SCIENCE · 2021 · IF 8.742

Construction of electro-neutral surface on dialysis membrane for improved toxin clearance and anti-coagulation/inflammation through saltwater fish inspired trimethylamine N-oxide (TMAO)

Yang Liu,Guiliang Li,Qiu Han,Haibo Lin,Qiang Li,Gang Deng,Fu Liu

Dialysis membranes capable of preventing coagulation and inflammation and achieving high toxin clearances are highly desired for clinical hemodialysis. Here, we constructed an electro-neutral and hydrophilic surface on Polysulfone (PSf) membrane, which both improved the hemocompatibility and toxin clearance. The membrane surface was modified with trimethylamine N-oxide (TMAO) through Michael addition reaction and subsequent crosslinking with glycidyl ether oxypropyl trimethoxysilane (KH560). Saltwater fish inspired zwitterionic monomer TMAO without spacers between positive and negative headgroups is thought to generate a hydrated and net-charged layer that prevents non-specific plasma proteins and platelets adsorption and activation. Coagulation time, serine protease Factor XIIa, bradykinin (BK), kallikrein (KLK) and anaphylatoxins (C3, C5 and SC5b-9) were examined to explore blood compatibility. All results showed that the highly hydrated and electro-neutral surface could efficiently alleviate the activation of the coagulation cascade, kallikrein-kinin system (KKS) and complement system simultaneously. Furthermore, the modified PSf membrane is favorable to toxins clearance (e.g., urea, creatine, lysozyme and vitamin B12) during simulated dialysis process. It is manifested that the TMAO based surface modification is feasible for improving the hemocompatibility and toxin clearance of dialysis membranes.

研究领域: 生物医学工程 · 材料科学 · 血液学
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Materials Science & Engineering C-Materials for Biological Applications · 2021 · IF 7.328

Cellulose acetate-polyvinyl alcohol blend hemodialysis membranes integrated with dialysis performance and high biocompatibility

Ofaira Azhar,Zaib Jahan,Farooq Sher,Muhammad Bilal Khan Niazi,Salik Javed Kakar,Muhammad Shahid

Hemodialysis considered as therapy of end-stage renal disease (ESRD) for the separation of protein and uremic toxins based on their molecular weights using semi-permeable membranes. Cellulose Acetate (CA) hemodialysis membrane has been widely used in the biomedical field particularly for hemodialysis applications. The main issue of CA membrane is less selectivity and hemocompatibility. In this study, to enhance the filtration capability and biocompatibility of CA hemodialysis membrane modified by using Polyvinyl Alcohol (PVA) and Polyethylene Glycol (PEG) as additives. CA-PVA flat sheet membranes were cast by phase inversion method, and separation was done by dead-end filtration cell. The synthesized membranes were described in terms of chemical structure using Fourier Transform Infrared Spectroscopy (FTIR) and morphology by Scanning Electron Microscopy (SEM), Atomic Force Microscopy (AFM), pure water flux, solute permeation, and protein retention. Biocompatibility of the membranes was tested by the platelet adherence, hemolysis ratio, thrombus formation, and plasma recalcification time. SEM images exposed that the CA-PVA membrane has a uniform porous structure. 42.484 L/m 2  h is the maximum pure water flux obtained. The CA-PVA rejected up to 95% of bovine serum albumin (BSA). A similar membrane separated 93% of urea and 89% of creatinine. Platelet adhesion and hemolysis ratio of casted membranes were less than the pure CA membrane. Increased clotting time and less thrombus formation on the membrane's surface showed that the fabricated membrane is biocompatible. CA-PVA hemodialysis membranes are more efficient than conventional reported hemodialysis membranes. It revealed that CA-PVA is high performing biocompatible hemodialysis membrane.

CAS / MDL: 25322-68-3
研究领域: 医学材料 · 生物医学工程
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ACS Applied Bio Materials · 2018 · IF 0

Polydopamine-Assisted Immobilization of Copper Ions onto Hemodialysis Membranes for Antimicrobial

Jun Xing,Qiyou Wang,Tianrui He,Zhengnan Zhou,Dafu Chen,Xin Yi,Zhengao Wang,Renxian Wang,Guoxin Tan,Peng Yu,Chengyun Ning

The hemodialysis therapy is the primary treatment for the end-stage renal disease (ESRD) patients to extend their lives. To reduce the pathogenic infection during hemodialysis treatment, mussel-inspired polydopamine (PDA) was self-polymerized onto poly(ether sulfone) (PES) membranes to immobilize copper ions, because PDA coating could firmly adhere to the PES membranes and immobilize antimicrobial metal ions with its functional groups. The immobilized copper ions through PDA can penetrate deeply into the inner surface of the pores of PES membrane. Water permeability test further indicates PDA coating can obviously enhance the hydrophilicity of PES membranes. And copper ion immobilized PES membranes showed effective antibacterial activity with a relative safe release amount of copper ions (below 1 ppm). Furthermore, hemolysis test results revealed that PDA-assisted antibacterial PES membranes can relieve red blood cells damage compared to the pure PES membranes. To sum up, PES hemodialysis membranes obtained the antibacterial ability by the PDA-assisted copper ion immobilization, which can reduce the abuse of antibiotics and is beneficial to the patient suffering from kidney disease.

研究领域: 材料科学 · 生物医学工程 · 肾病学
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FOOD CHEMISTRY · 2015 · IF 3.391

Integrated method of thermosensitive triblock copolymer–salt aqueous two phase extraction and dialysis membrane separation for purification of lycium barbarum polysaccharide

Yun Wang,Xiaowei Hu,Juan Han,Liang Ni,Xu Tang,Yutao Hu,Tong Chen

A polymer–salt aqueous two-phase system (ATPS) consisting of thermosensitive copolymer ethylene-oxide-b-propylene-oxide-b-ethylene-oxide (EOPOEO) and NaH 2 PO 4 was employed in deproteinization for lycium barbarum polysaccharide (LBP). The effects of salt type and concentration, EOPOEO concentration, amount of crude LBP solution and temperature were studied. In the primary extraction process, LBP was preferentially partitioned to the bottom (salt-rich) phase with high recovery ratio of 96.3%, while 94.4% of impurity protein was removed to the top (EOPOEO-rich) phase. Moreover, the majority of pigments could be discarded to top phase. After phase-separation, the LBP in the bottom phase was further purified by dialysis membrane to remove salt and other small molecular impurities. The purity of LBP was enhanced to 64%. Additionally, the FT-IR spectrum was used to identify LBP. EOPOEO was recovered by a temperature-induced separation, and reused in a new ATPS. An ideal extraction and recycle result were achieved.

研究领域: 生物化学 · 分离技术 · 高分子化学
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ACS Applied Materials & Interfaces · 2015 · IF 6.723

Poly(Lactic Acid) Hemodialysis Membranes with Poly(Lactic Acid)-block-Poly(2-Hydroxyethyl Methacrylate) Copolymer As Additive: Preparation, Characterization, and Performance

Lijing Zhu,Fu Liu,Xuemin Yu,Lixin Xue

Poly(lactic acid) (PLA) hemodialysis membranes with enhanced antifouling capability and hemocompatibility were developed using poly(lactic acid)-block-poly(2-hydroxyethyl methacrylate) (PLA–PHEMA) copolymers as the blending additive. PLA–PHEMA block copolymers were synthesized via reversible addition–fragmentation (RAFT) polymerization from aminolyzed PLA. Gel permeation chromatography (GPC) and 1H-nuclear magnetic resonance (1H NMR) were applied to characterize the synthesized products. By blending PLA with the amphiphilic block copolymer, PLA/PLA–PHEMA membranes were prepared by nonsolvent induced phase separation (NIPS) method. Their chemistry and structure were characterized with X-ray photoelectron spectroscopy (XPS), scanning electron microscope (SEM) and atomic force microscopy (AFM). The results revealed that PLA/PLA–PHEMA membranes with high PLA–PHEMA contents exhibited enhanced hydrophilicity, water permeability, antifouling and hemocompatibility. Especially, when the PLA–PHEMA concentration was 15 wt %, the water flux of the modified membrane was about 236 L m–2 h–1. Its urea and creatinine clearance was more than 0.70 mL/min, lysozyme clearance was about 0.50 mL/min, BSA clearance was as less as 0.31 mL/min. All the results suggest that PLA–PHEMA copolymers had served as effective agents for optimizing the property of PLA-based membrane for hemodialysis applications.

研究领域: 生物材料 · 医学工程 · 高分子化学
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JOURNAL OF MEMBRANE SCIENCE · 2022 · IF 10.53

mPEG-b-PES-b-mPEG-based candidate hemodialysis membrane with enhanced performance in sieving, flux, and hemocompatibility

Jian Ren,Xin Yang,Weixing Yan,Xia Feng,Yiping Zhao,Li Chen

The efficiency of the hemodialysis membrane has been widely improved by blending small molecular additives and modifying the membrane surface for patients with chronic or acute kidney disease. However, a qualified sieving property, flux, and hemocompatibility are intractable to give consideration simultaneously, while the elution of small-molecular additives and modifiers easily cause coagulation, complement activation, etc. Fortunately, the BCP methoxy polyethylene glycol-polyethersulfone-block-methoxy polyethylene glycol (mPEG -b- PES -b- mPEG) based membranes exhibiting great potential for sieving in middle molecular toxin and compatibility between mPEG -b- PES -b- mPEG and PES, is nearly unfeasible elution during hemodialysis, by reason of including bounded hydrophilic segments by chemical bonds. Here, the mPEG -b- PES -b- mPEG is synthesized to fabricate the membranes, including blend membranes and BCP membrane. As a result, the blend membranes have shown an increasing flux, hemocompatibility, and sieving of lysozyme with the increasing cooperation of mPEG-b-PES-b-mPEG, the block copolymer (BCP) mPEG -b- PES -b- mPEG membrane has shown better balance than the blend membranes in flux, sieving, and hemocompatibility. Besides, for exploring further possibilities, the typical blend membrane M4 (mPEG- b -PES- b -mPEG: 20%, PES: 5%) and BCP membrane M5 (mPEG- b -PES- b -mPEG: 25%) are post tailored by ethanol at 50 °C for 2 h. This process leading the typical membranes to an efficient flux (M5-P: 442.22 L m −2  h −1 ) and sieving performances (M5-P: the urea and lysozyme sieving of 96.43% and 74.97%) due to the effect of ethanol at the micro-molecular chain movements and microspheres transfer. Our work presents BCP mPEG -b- PES -b- mPEG a promising future in hemodialysis membranes according to the superior performances of flux and sieving.

研究领域: 材料科学 · 生物医学工程 · 纳米技术
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JOURNAL OF MEMBRANE SCIENCE · 2023 · IF 9.5

Vapor-based hybrid grafting of heparin-like coating for dialysis membranes with enhanced hemocompatibility

Ruhao Zhang,Xiao Shi,Xiaocheng Huang,Jiaqi Zhao,Peng Lu,Yu He,Fu Liu,Wenna Liu,Yumin Ye

Heparin is commonly used to improve the hemocompatibility of biomaterials, but high doses of heparin may cause significant side effect in clinical applications. Thus, heparin-mimicking surfaces have been urgently explored to reduce the use of heparin. In this work, heparin-like coating was deposited on polylactide (PLA) dialysis membranes using one-step hybrid grafting of a carboxyl-enriched poly(methacrylic acid) (pMAA) coating via initiated chemical vapor deposition (iCVD). The hybrid grafting was conducted by depositing a prime layer of poly(methacrylic acid- co -ethylene glycol dimethacrylate) (p(MAA- co -EGDMA)) copolymer followed by immediate in situ grafting of a pMAA homopolymer layer. The grafting parameters were systematically studied to obtain the maximum grafting density of pMAA. The resulting membrane with maximized surface functionality shows strong hydrophilicity with a water contact angle of 33° without affecting its permeability, excellent suppression of platelet adhesion and deformation, and significantly lengthened clotting time (APTT, TT, and PT prolonged to 308.4 s, 31.0 s, and 31.9 s, respectively). The substantially enhanced hemocompatibility is attributed to the abundant carboxyl groups achieved by hybrid grafting, which effectively disrupts the coagulation cascade. This facile iCVD grafting method can be a promising candidate for improving the hemocompatibility of biomaterials, such as dialysis membranes, catheters, and implants.

研究领域: 生物材料 · 生物医学工程 · 血液透析 · 表面化学
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ACS Applied Materials & Interfaces · 2020 · IF 8.758

Hierarchical Surface Architecture of Hemodialysis Membranes for Eliminating Homocysteine Based on the Multifunctional Role of Pyridoxal 5′-phosphate

Peng Jiang,Yang He,Yiping Zhao,Li Chen

Patients with end-stage renal disease are prone to developing a complication of hyperhomocysteinemia, manifesting as an elevation of the homocysteine (Hcy) concentration in human plasma. However, Hcy as a protein-bound toxin is barely removed by conventional hemodialysis membranes. Here, we report a novel hemodialysis membrane by preparing a bioactive coating of pyridoxal 5′-phosphate (PLP) and adding biocompatible hyperbranched polyglycerol (HPG) brushes to achieve Hcy removal. The dip-applied PLP coating, a coenzyme with a role in Hcy metabolism, dramatically promoted a decrease in the Hcy concentration in human plasma. Moreover, the aldehyde group of PLP had an intrinsic chemical reactivity toward the terminal amino group to immobilize the HPG brushes on the hemodialysis membrane surface. The hierarchical PLP–HPG layer-functionalized membranes had a high efficacy for eliminating Hcy, with a concentration from the initial stage of 150 μmol/L reduced to a nearly normal level of 20 μmol/L in simulated dialysis. By analyzing the impact of HPG brushes with various chain lengths, we found that HPG brushes with a medium length enabled the PLP coating with the bioactive function of Hcy conversion to additionally protect Hcy-attacked target cells by providing excellent hydrophilicity and a dense enough chain volume overlap of the hyperbranched architecture. Simultaneously, the densely packed HPG brushes generated a maximal steric and hydration barrier that significantly improved biofouling resistance against blood proteins. The optimally functionalized membranes showed a clearance of 83.1% urea and 49.6% lysozyme and a rejection of 96.0% bovine serum albumin. The diversely functionalized PLP–HPG layers demonstrate a potential route for a more integrated hemodialysis membrane that can cope with the urgent issue of hyperhomocysteinemia in clinical hemodialysis therapy.

研究领域: 生物材料 · 生物医学工程 · 肾脏治疗
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JOURNAL OF MEMBRANE SCIENCE · 2025 · IF 9

Engineering cross-linked polyvinyl alcohol/ polyethersulfone hemodialysis membrane for simultaneously inhibiting platelet adhesion and activation and alleviating severe oxidative stress

Jian Ren,Lin Xu,Xianda Liu,Dongmei Tong,Chunji Jiang,Shujing Wang,Xiang Zhang,Ran Wei,Weifeng Zhao,Changsheng Zhao

End-stage kidney dialysis therapy is often accompanied by severe oxidative stress, which significantly increases patient mortality. To address this issue, anti-oxidative hemodialysis membranes have emerged. Meanwhile, the surface of hemodialysis membranes also faces poor blood compatibility and thrombocytopenia problems, closely related to platelet activation and adhesion. In this work, we develop a series of polyethersulfone@ polyvinyl alcohol- l -Arginine (PES@PVA-L-Arg) gel membranes. Specifically, polyvinyl alcohol (PVA) macromolecules are crosslinked with N 1 -(4-boronobenzyl)- N 3 -(4-boronophenyl)- N 1 , N 1 , N 3 , N 3 -tetramethylpropane-1,3-diam-inium (TSPBA), while l -Arginine (L-Arg) molecules are simultaneously embedded into the PES/PVA membrane as a nitric oxide (NO) donor. The results reveal that the PES@PVA1-L-Arg inhibits the platelets' adhesion and activation onto the surface of the membrane, with the number of activated platelets reduced by 38 % compared to the PES membrane. This inhibition is achieved through the hydrated PVA layer and the release of NO in a reactive oxygen species (ROS) microenvironment. Additionally, the PES@PVA1-L-Arg membrane demonstrates superior ROS scavenging capacity, neutralizing 40.62 % of ABTS• + via TSPBA and 73.66 % of H 2 O 2 through the combined effects of TSPBA and L-Arg. Basically, the hemodialysis function meets the requirement under the simulated scenario, with the bovine serum albumin rejection of 96.09 %, lysozyme, and urea sieving coefficients of 77.85 % and 92.03 %, respectively. Moreover, the safety of the membranes is confirmed by hemocompatibility tests, including clotting tests, blood cell counting statistics tests, C3a and C5a levels, and hemolysis ratio. Overall, our work presents a promising PES@PVA1-L-Arg membrane that not only inhibits platelet activation and adhesion but also alleviates severe oxidative stress for clinical hemodialysis.

研究领域: 生物医学工程 · 材料科学 · 肾脏病学 · 血液学 · 生物化学
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CHEMICAL ENGINEERING JOURNAL · 2024 · IF 13.3

Inhibiting advanced glycation end products (AGEs) of high-performance hemodialysis membranes self-assembled by gallic acid and Ti3C2Tx MXene

Qiqi Wang,Changjun Mu,Ya'nan Yu,Xia Feng,Yang He,Li Chen

Current patients with chronic kidney disease (CKD) suffer from either accumulation of advanced glycation end products (AGEs) or inefficient clearance of the middle molecule uremic toxins, threatening their long-term survival rate. In particular, conventional hemodialysis membranes cannot prevent AGEs formation because of continuous oxidative stress from reactive oxygen species (ROS). Herein, a persistent ROS scavenging and efficient uremic toxin clearance of hemodialysis membrane is proposed by the in situ deposition of a gallic acid-Ti 3 C 2 T x MXene (GA-MXene) n multilayers through a self-assembly method, where n denotes the number of deposition layers. These hemodialysis membranes have a highly interconnecting composite laminate with tunable pore size. In the dialysis experiment, the (GA-MXene) 2 membrane with the vertical nano-slits shows the highest middle molecule uremic toxin clearance of 80.0% compared with state-of-the-art hemodialysis membranes, which has been approximately equal to the clearance of small molecule urea. Furthermore, GA conferring efficient ROS scavenging rate over dialysis treatment time allows anti-oxidative activities to inhibit AGEs’ formation. (GA-MXene) n multilayers enhanced the serum total antioxidant capacity and suppressed lipid peroxidation from oxidative damage. Ultimately, the (GA-MXene) n hemodialysis membranes provide excellent anticoagulant properties and cytocompatibility through the heparin-mimicking sulfonated Ti 3 C 2 T x MXene and biological activity of GA. This work facilitates the blood purification application of MXenes and opens up an avenue for developing functional multilayers for high-performance hemodialysis membranes and beyond.

CAS / MDL: 149-91-7
研究领域: 材料科学 · 生物医学工程 · 纳米技术 · 肾脏医学
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