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JOURNAL OF MEMBRANE SCIENCE · 2018 · IF 6.578

Preparation and evaluation of a self-anticlotting dialyzer via an interface crosslinking approach

Hui Wang,Wenjia Hou,Fu Liu,Qiu Han,Tiantian Li,Haibo Lin,Gang Deng,Jidong He

It is challenging to improve the hemocompatibility of commercial dialyzers packaging more than 10,000 fibers. Herein, we report the preparation and evaluation of a self-anticlotting Polysulfone dialyzer via an interface crosslinking approach. By modulating the conformation of sulfate, carboxyl groups and pyrrolidone (VP) in heparin-like polymers, the hemocompatibility of the dialyzer was significantly improved. It was found that the sequential structure of functional groups influenced the anticoagulant performances substantially. The hollow fiber modified by the blended polymer (Poly (N-vinyl-2-pyrrolidone- co -triethoxyvinylsilane) and poly (Sodium 4-vinylbenzenssulfonate- co -triethoxyvinylsilane- co -Acrylic acid) (P(VP-VTES)- b -P(SSNa-VTES-AA))) exhibited better hemocompatibility than the contrast membrane modified by poly (Acrylic acid- co -triethoxyvinylsilane- co -N-vinyl-2-pyrrolidone- co - - co -Sodium 4-vinylbenzenssulfonate) (P(AA-VTES-VP-SSNa)). The chemical composition was determined by X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectra (FTIR). The morphology of the hollow fiber membranes was observed by a scanning electron microscopy (SEM). The thrombin time (TT), plasma fibrinogen (FIB), activated partial thromboplastin time (APTT), prothrombin time (PT) and protein adsorption were measured to examine the hemocompatibility. The modified hollow fiber showed self-anticlotting properties with excellent protein resistance, remarkably prolonged coagulation time (APTT > 600 s), suppressed complement activation and nontoxicity to osteoblasts. The modified dialyzer showed practicable ultrafiltration coefficient and clearance performance, indicating its great potential application in dialysis treatment.

研究领域: 生物医学工程 · 材料科学 · 血液透析
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CARBOHYDRATE POLYMERS · 2018 · IF 5.158

A mussel-inspired approach towards heparin-immobilized cellulose gel beads for selective removal of low density lipoprotein from whole blood

Yupei Li,Mei Han,Yilin Wang,Qiang Liu,Weifeng Zhao,Baihai Su,Changsheng Zhao

In this study, we report a mussel-inspired approach to fabricate heparin-immobilized cellulose (HeTaCe) gel beads with self-anticoagulative and biocompatible properties which can selectively remove low density lipoprotein (LDL) from whole blood directly. First, a phase inversion technique was applied to prepare cellulose gel beads. Then the as-prepared gel beads were dipped into a mixed solution of heparin and tannic acid in phosphate buffered saline (PBS, pH 8.5) to obtain HeTaCe gel beads. Blood compatibility experiments indicated that the HeTaCe gel beads could suppress complement activation as well as contact activation and prolong the clotting times to the upper detect limits (activated partial thromboplastin time >600 s and thrombin time >180 s) of the automated blood coagulation analyzer. An ideal adsorption capacity of LDL in vitro was achieved by the HeTaCe gel beads with an amount of 79.1 mg/g. Besides, dynamic column adsorption test further demonstrated a selective adsorption of LDL without a significant reduction of high density lipoprotein (HDL) in a simulative hemoperfusion system. It is believed that the HeTaCe gel beads will be quite appealing to future clinical practice aiming at lowering LDL and improving the outcomes of patients with high cardiovascular risk.

研究领域: 生物材料 · 医学工程 · 心血管疾病治疗
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JOURNAL OF MEMBRANE SCIENCE · 2022 · IF 10.53

Anticoagulant biomimetic consecutive gas exchange network for advanced artificial lung membrane

Yunbo Feng,Qian Wang,Lunhao Zhi,Shudong Sun,Changsheng Zhao

Artificial lung membrane as extracorporeal blood-gas barriers could execute similar functions as human alveoli, whereby accomplish blood gas exchange process, providing imperative life support for patients with cardiopulmonary failure. However, the gas exchange performance for current membranous modules is restrained to the dense polymer matrix with low CO 2 permeability. Meanwhile, it has long been difficult to balance the contradiction between haemorrhagic risk generated by heparin systemic anticoagulation and thrombogenesis during extracorporeal blood circulation. Here, inspired by the natural mammalian alveoli, a biomimetic consecutive gas exchange network (CGEN) is constructed on porous PES substrate by using aperture-modulated UIO-66-NH 2 nanoparticles and hydrophilic CO 2 -affinitive polymer matrix to simulate the physiological structures and gas exchange features of human alveoli in vitro. The porous MOF particles within CGEN establish the main gas exchange channels, which not only enhance the total gas permeation, but also improve the CO 2 /O 2 permselectivity to 13.17, approaching to the level of natural alveoli. Additionally, the prepared composite membrane with good hemocompatibility could effectively inhibit the formation of thrombus and provide a reliable local self-anticoagulation state during extracorporeal blood circulation. Overall, this biomimetic thin film composite membrane could provide new ideals for the preparation of advanced artificial lung membrane.

研究领域: 生物医学工程 · 材料科学 · 组织工程
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Journal of Materials Chemistry B · 2020 ·Vol. 8 ·期 9 ·1960-1970 · IF 5.344

Construction of Kevlar nanofiber/graphene oxide composite beads as safe, self-anticoagulant, and highly efficient hemoperfusion adsorbents

Ye Yang,Shiqi Yin,Chao He,Xizheng Wu,Jiarui Yin,Jue Zhang,Lang Ma,Weifeng Zhao,Chong Cheng,Changsheng Zhao

Recently emerged hemoperfusion absorbents, e.g. ion-exchange resin, activated carbon, and other porous materials, provide numerous novel possibilities to cure chronic liver failure (CLF) and renal failure (CRF). However, the limited adsorption performance and unsatisfactory blood compatibility significantly impede the development of the absorbents. Hence, designing safe and self-anticoagulant hemoperfusion absorbents with robust toxin clearance remains a considerable challenge. Here, brand new Kevlar-based composite gel beads for hemoperfusion are prepared by interface assembly based on π–π interaction. First, Kevlar nanofiber–graphene oxide (K–GO) beads are produced by liquid–liquid phase separation. Then, sodium p-styrenesulfonate (SS) is adsorbed onto the K–GO interface by π–π interaction and initiated to achieve the composite gel (K–GO/PSS) beads with an interfacial crosslinked structure. Such composite gel beads possess superior mechanical strength and self-anticoagulation capability, owing to the dual-network structure and heparin-mimicking gel structure, respectively. Furthermore, the K–GO/PSS beads show robust adsorption capacities for different kinds of toxins due to their strong charge and π–π interactions. A simulated hemoperfusion experiment in vitro demonstrates that the concentrations of the toxins in the blood can be restored to normal values within 30 minutes. In general, we envision that such composite gel beads will provide new strategies for future clinical CLF and CRF treatments.

研究领域: 材料科学 · 生物医学工程 · 血液透析技术
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Nature Communications · 2023 ·Vol. 14 ·期 1 ·1-20 · IF 16.6

Self-anticoagulant sponge for whole blood auto-transfusion and its mechanism of coagulation factor inactivation

Xu Tao,Ji Haifeng,Xu Lin,Cheng Shengjun,Liu Xianda,Li Yupei,Zhong Rui,Zhao Weifeng,Kizhakkedathu Jayachandran N.,Zhao Changsheng

Clinical use of intraoperative auto-transfusion requires the removal of platelets and plasma proteins due to pump-based suction and water-soluble anticoagulant administration, which causes dilutional coagulopathy. Herein, we develop a carboxylated and sulfonated heparin-mimetic polymer-modified sponge with spontaneous blood adsorption and instantaneous anticoagulation. We find that intrinsic coagulation factors, especially XI, are inactivated by adsorption to the sponge surface, while inactivation of thrombin in the sponge-treated plasma effectively inhibits the common coagulation pathway. We show whole blood auto-transfusion in trauma-induced hemorrhage, benefiting from the multiple inhibitory effects of the sponge on coagulation enzymes and calcium depletion. We demonstrate that the transfusion of collected blood favors faster recovery of hemostasis compared to traditional heparinized blood in a rabbit model. Our work not only develops a safe and convenient approach for whole blood auto-transfusion, but also provides the mechanism of action of self-anticoagulant heparin-mimetic polymer-modified surfaces.

研究领域: 血液学 · 外科技术 · 材料科学 · 生物医学工程
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