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ACS Biomaterials Science & Engineering · 2024 · IF 5.4

Generalized Multifunctional Coating Strategies Based on Polyphenol-Amine-Inspired Chemistry and Layer-by-Layer Deposition for Blood Contact Catheters

Jiahao Du,Xiaoting Zhang,Wenlong Li,Miao Wang,Xi Zhou,Lei Ren

Blood-contacting catheters play a pivotal role in contemporary medical treatments, particularly in the management of cardiovascular diseases. However, these catheters exhibit inappropriate wettability and lack antimicrobial characteristics, which often lead to catheter-related infections and thrombosis. Therefore, there is an urgent need for blood contact catheters with antimicrobial and anticoagulant properties. In this study, we employed tannic acid (TA) and 3-aminopropyltriethoxysilane (APTES) to create a stable hydrophilic coating under mild conditions. Heparin (Hep) and poly(lysine) (PL) were then modified on the TA-APTES coating surface using the layer-by-layer (LBL) technique to create a superhydrophilic TA/APTES/(LBL)4 coating on silicone rubber (SR) catheters. Leveraging the superhydrophilic nature of this coating, it can be effectively applied to blood-contacting catheters to impart antibacterial, antiprotein adsorption, and anticoagulant properties. Due to Hep’s anticoagulant attributes, the activated partial thromboplastin time and thrombin time tests conducted on SR/TA-APTES/(LBL)4 catheters revealed remarkable extensions of 276 and 103%, respectively, when compared to uncoated commercial SR catheters. Furthermore, the synergistic interaction between PL and TA serves to enhance the resistance of SR/TA-APTES/(LBL)4 catheters against bacterial adherence, reducing it by up to 99.9% compared to uncoated commercial SR catheters. Remarkably, the SR/TA-APTES/(LBL)4 catheter exhibits good biocompatibility with human umbilical vein endothelial cells in culture, positioning it as a promising solution to address the current challenges associated with blood-contact catheters.

研究领域: 生物材料学 · 医学工程 · 表面化学
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Materials Science & Engineering C-Materials for Biological Applications · 2017 · IF 4.164

The effect of hirudin modification of silk fibroin on cell growth and antithrombogenicity

Qiongyu Wang,Fangfang Tu,Yunfei Liu,Yujin Zhang,Helei Li,Zhao Kang,Yin Yin,Jiannan Wang

Thrombus formation remains a particular challenge for small-diameter vascular grafts. In this study, the direct thrombin inhibitor hirudin (Hir) was used to modify silk fibroin films in an attempt to enhance its antithrombogenic properties. Hir was successfully attached to silk fibroin and uniformly distributed in the regenerative material. Hir-modified films showed good cytocompatibility, and supported adhesion and proliferation of fibroblasts (L929), human umbilical vascular endothelial cells (HUVECs) and human aortic smooth muscle cells (HASMCs). Proliferation of HAVSMCs was inhibited by increasing Hir concentration. Activated partial thrombin time (APTT), prothrombin time (PT) and thrombin time (TT) of Hir-modified silk fibroin tubular scaffolds (SFTSs) were all increased markedly compared with fresh rabbit blood, ethanol-treated SFTS and unmodified SFTS, demonstrating the improved antithrombogenicity of SFTSs following modification with Hir.

CAS / MDL: 3326-32-7
研究领域: 生物医学工程 · 材料科学 · 血液学
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MACROMOLECULAR BIOSCIENCE · 2016 ·Vol. 17 ·期 2 ·1600281 · IF 3.68

Super-Anticoagulant Heparin-Mimicking Hydrogel Thin Film Attached Substrate Surfaces to Improve Hemocompatibility

Min He,Xiaofei Cui,Huiyi Jiang,Xuelian Huang,Weifeng Zhao,Changsheng Zhao

In this study, heparin-mimicking hydrogel thin films are covalently attached onto poly(ether sulfone) membrane surfaces to improve anticoagulant property. The hydrogel films display honeycomb-like porous structure with well controlled thickness and show long-term stability. After immobilizing the hydrogel films, the membranes show excellent anticoagulant property confirmed by the activated partial thromboplastin time values exceeding 600 s. Meanwhile, the thrombin time values increase from 20 to 61 s as the sodium allysulfonate proportions increase from 0 to 80 mol%. In vitro investigations of protein adsorption and blood-related complement activation also confirm that the membranes exhibit super-anticoagulant property. Furthermore, gentamycin sulfate is loaded into the hydrogel films, and the released drug shows significant inhibition toward E. coli bacteria. It is believed that the surface attached heparin-mimicking hydrogel thin films may show high potential for the applications in various biological fields, such as blood contacting materials and drug loading materials.

研究领域: 生物材料学 · 血液相容性研究
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2017 · IF 3.671

Heparin-mimetic polyurethane hydrogels with anticoagulant, tunable mechanical property and controllable drug releasing behavior

Yuan Chen,Rui Wang,Yonghui Wang,Weifeng Zhao,Shudong Sun,Changsheng Zhao

In the present study, novel heparin-mimetic polyurethane hydrogels were prepared by introducing chemical crosslinked sulfated konjac glucomannan (SKGM). Scanning electron microscopy (SEM) results indicated that the introduction of SKGM and the increase of the molecular weight of diol segments could enlarge the pore sizes of the hydrogels. The swelling behavior corresponded with the SEM results, and the hydrogels could absorb more water after the modification. The modification also led to an improvement in the mechanical property. Meanwhile, the SKGM and the modified polyurethane hydrogels showed excellent hemocompatibility. The thromboplastin time of SKGM could reach up to 182.9   s. Gentamycin sulfate (GS) was used as a model drug to be loaded into the hydrogels, and the loading amount was increased ca. 50% after the introduction of SKGM, thus resulting in high bactericidal efficiency. The results indicated that the introduction of SKGM and the alternation in the diol’s molecular weight bestowed polyurethane hydrogels with promising properties of integrated blood-compatibility, mechanical properties and drug loading-releasing behavior. Therefore, the heparin-mimetic multifunctional polyurethane hydrogels have great potential to be used in biomedical applications.

研究领域: 生物材料学 · 医学工程 · 药剂学
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RSC Advances · 2015 ·Vol. 5 ·期 116 ·95710-95716 · IF 3.84

Preparation and characterization of a thrombin inhibitor grafted polyethersulfone blending membrane with improved antithrombotic property

Shuang-Shuang Fu,Jian-Ping Ning,Xiao-Hua Liao,Xiao Fu,Zheng-Bo Yang

Systemic anticoagulation is indispensable for hemodialysis patients to prevent clotting, but patients at high risk of bleeding cannot be given systemic anticoagulation. Hemodialyzer membrane modification maybe an effective program to solve this problem. In this study, we chose argatroban, a direct thrombin inhibitor, to modify a polyethersulfone (PES) membrane. Firstly, we prepared an argatroban (AG) grafted polyethersulfone (PES-AG) matrix by acetylating, oxidating and amidation reactions. Then, PES-AG was blended with PES at ratios of 2 : 1 and 1 : 1 respectively to prepare a PES/PES-AG membrane by using a phase inversion technique. FTIR and 1H NMR spectroscopy were used to confirm that argatroban was grafted to PES successfully. Scanning electron microscopy (SEM) was used to observe the characteristic morphology of the membranes. Activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT) and platelet function were detected to evaluate the antithrombotic property of the modified membrane. The results indicate that the antithrombotic property of the PES/PES-AG (1 : 1) membrane was superior to other three groups.

研究领域: 生物医学工程 · 材料科学 · 血液学
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COLLOIDS AND SURFACES B-BIOINTERFACES · 2025 · IF 5.6

Sulfonated covalent organic frameworks (COF)/polyethersulfone (PES) membrane with enhanced hemocompatibility for blood oxygenation

Yue Huang,Lunhao Zhi,Chong Cheng,Qiang Wei,Shudong Sun,Changsheng Zhao

In extracorporeal membrane oxygenation (ECMO) treatment, designing membrane with self-anticoagulant properties can solve problems resulting from the adverse effect of anticoagulants. In this study, 2,4,6-Triformylphloroglucinol (Tp) and 2,5-Diaminobenzenesulfonic acid (Pa-SO 3 H) were applied to grow a sulfonated COF film in situ on the polyethersulfone (PES) membrane. The introduction of sulfonic groups increased the hydrophilicity and electronegativity of the TpPa COF film, improved its anti-protein adhesion properties, maintained the normal morphology of blood cells, and endowed the COF film with antithrombotic properties. In the porcine blood circulation test, the duration to increase So 2 (O 2 saturation) from ∼75–95 % in TpPa-SO 3 H COF/PES membrane (M-TpPa-SO 3 H) was 70 min shorter than that in TpPa COF/PES membrane (M-TpPa). This preparation method is applicable to the preparation of not only flat membranes, but also hollow fiber membranes. These findings emphasize the potential of M-TpPa-SO 3 H in ECMO applications, providing superior antithrombotic property and CO 2 efflux potential.

CAS / MDL: 151-21-3 9048-46-8
研究领域: 生物医学工程 · 材料科学 · 血液学
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2018 · IF 3.909

Preparation and anticoagulant properties of heparin-like electrospun membranes from carboxymethyl chitosan and bacterial cellulose sulfate

Weikang Song,Qinhuan Zeng,Xueqiong Yin,Li Zhu,Tao Gong,Changjiang Pan

Heparin-like membranes (CPBS) with nanofibers (approximate diameters of 100–500 nm) were prepared through electrospinning of a blended solution of carboxymethyl chitosan nanoparticle (CMCN, diameters 483 nm) and poly (vinyl alcohol) (CMCN/PVA) onto the surface of modified bacterial cellulose sulfate (BCS) membranes. SEM images confirmed that the CMCN were stretched to nanofibers during electrospinning. The presence of BCS on the collector of electrospinning machine increased the spinnability of CMCN/PVA solution. FTIR and XPS measurement revealed that there were SO 3 − , COO − , and OH groups on the surface of CPBS membrane, expressing structural similarity to heparin. CPBS membranes maintained hydrophilicity and the glutaraldehyde crosslinked CPBS membrane was stable in water. The clotting time and platelet adhesion experiments expressed the anticoagulant properties of CPBS. The APTT , TT and PT of CPBS increased up to 116.0%, 189.8%, and 50% than those of the plasma, (67.4 s, 16.2 s, and 48.4 s, respectively). No platelets adhered onto the surface of CPBS. An inflammatory response was determined according to activation of the macrophages seeded onto the membranes.

研究领域: 生物材料学 · 医学工程 · 药剂学
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COLLOIDS AND SURFACES B-BIOINTERFACES · 2021 · IF 5.268

Enhanced hydrophilicity and anticoagulation of polysulfone materials modified via dihydroxypropyl, sulfonic groups and chitosan

Can Wang,Bingxian Lin,Yunren Qiu

A novel modified polysulfone (PSF) is successfully prepared for hemodialysis by grafting with a well-defined heparin-like polymer, sulfonated dihydroxypropyl chitosan (SDHPCS), which is obtained in proper sequence via alkalization of chitosan, etherification and sulfonation . PSF is modified via chloroacetyl chloride , and then, the chloroacylated polysulfone (CAPSF) with pristine PSF is transformed into CAPSF/PSF blend membrane via the phase inversion, followed introducing amino group into CAPSF on the surface and taking glutaraldehyde as bridge between modified PSF membrane and SDHPCS. The result of 1 H NMR spectrum of prepared CAPSF indicates that the degree of the substitution of chloroacetyl group . The SEM, EDS mapping, FTIR and XPS show that SDHPCS-g-PSF membranes are successfully prepared. The hydrophilicity of the membrane modified by SDHPCS is improved obviously, and the contact angle remarkably reduced from 87 ° to below 45°, exhibiting much better hydrophilicity. The hemocompatibility characterizations including BSA adsorption, Plasma recalcification time (PRT), hemolysis ratio (HR), activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT) also certificates that SDHPCS-g-PSF possesses lower BSA adsorption and enhanced blood compatibility.

研究领域: 生物医学工程 · 材料科学 · 血液学
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Journal of Materials Chemistry B · 2022 ·Vol. 10 ·期 40 ·8218-8234 · IF 7.571

Sulfonated, oxidized pectin-based double crosslinked bioprosthetic valve leaflets for synergistically enhancing hemocompatibility and cytocompatibility and reducing calcification

Mengyue Hu,Xu Peng,Shubin Shi,Chang Wan,Can Cheng,Ningning Lei,Xixun Yu

Clinically frequently-used glutaraldehyde (GA)-crosslinked bioprosthetic valve leaflets (BVLs) are still curbed by acute thrombosis, malignant immunoreaction, calcification, and poor durability. In this study, an anticoagulant heparin-like biomacromolecule, sulfonated, oxidized pectin (SAP) with a dialdehyde structure was first obtained by modifying citrus pectin with sulfonation of 3-amino-1-propane sulfonic acid and then oxidating with periodate. Notably, a novel crosslinking approach was established by doubly crosslinking BVLs with SAP and the nature-derived crosslinking agent quercetin (Que), which play a synergistic role in both crosslinking and bioactivity. The double crosslinked BVLs also presented enhanced mechanical properties and enzymatic degradation resistance owing to the double crosslinking networks formed via CN bonds and hydrogen bonds, respectively, and good HUVEC-cytocompatibility. The in vitro and ex vivo assay manifested that the double-crosslinked BVLs had excellent anticoagulant and antithrombotic properties, owing to the introduction of SAP. The subcutaneous implantation also demonstrated that the obtained BVLs showed a reduced inflammatory response and great resistance to calcification, which is attributed to quercetin with multiple physiological activities and depletion of aldehyde groups by hydroxyl aldehyde reaction. With excellent stability, hemocompatibility, anti-inflammatory, anti-calcification, and pro-endothelialization properties, the obtained double-crosslinked BVLs, SAP + Que-PP, would have great potential to substitute the current clinical GA-crosslinked BVLs.

CAS / MDL: 3687-18-1
研究领域: 生物医学工程 · 心血管材料科学
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JOURNAL OF COLLOID AND INTERFACE SCIENCE · 2014 · IF 3.552

Blood compatibility comparison for polysulfone membranes modified by grafting block and random zwitterionic copolymers via surface-initiated ATRP

Tao Xiang,Li-Sha Zhang,Rui Wang,Yi Xia,Bai-Hai Su,Chang-Sheng Zhao

For blood-contacting materials, good blood compatibility, especially good anticoagulant property is of great importance. Zwitterionic polymers have been proved to be resistant to nonspecific protein adsorption and platelet adhesion; however, their anticoagulant property is always inadequate. In this study, two kinds of zwitterionic copolymers (sulfobetaine methacrylate and sodium p-styrene sulfonate random copolymer and block copolymer) with sulfonic groups were covalently grafted from polysulfone (PSf) membranes via surface-initiated atom transfer radical polymerization (SI-ATRP) to improve blood compatibility. Field emission scanning electron microscopy (FE-SEM), attenuated total reflectance–Fourier transform infrared spectra (ATR–FTIR), X-ray photoelectron spectroscopy (XPS), and static water contact angle (WCA) were applied to characterize the morphologies, chemical compositions and hydrophilicity of the modified membranes. All the zwitterionic copolymer modified membranes showed improved blood compatibility, especially the anticoagulant property was obviously enhanced compared to the pristine PSf and simple zwitterionic polymer modified membranes. We also found that the random copolymer modified membranes showed better resistance to platelet adhesion than the block copolymer modified membranes. The zwitterionic copolymer modified membranes with integrated antifouling property and blood compatibility provided wide choice for specific applications such as hemodialysis, hemofiltration, and plasma separation.

研究领域: 生物材料 · 医学工程 · 高分子化学
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ACS Applied Materials & Interfaces · 2019 · IF 8.456

Programmed Release of Multimodal, Cross-Linked Vascular Endothelial Growth Factor and Heparin Layers on Electrospun Polycaprolactone Vascular Grafts

Dongfang Wang,Xiaofeng Wang,Zhi Zhang,Lixia Wang,Xiaomeng Li,Yiyang Xu,Cuihong Ren,Qian Li,Lih-Sheng Turng

Viable tissue-engineering small-diameter vascular grafts should support rapid growth of an endothelial cell layer and exhibit long-term antithrombogenic property. In this study, multiple layers of various bioactive molecules, such as vascular endothelial growth factor (VEGF) and heparin, on an electrospun polycaprolactone scaffold have been developed through repeated electrostatic adsorption self-assembly (up to 20 layers), followed by genipin cross-linking. Programmed and sustained release of biomolecules embedded within the multilayered structure can be triggered by matrix metallopeptidase 2 enzyme in vitro. The result is an early and full release of VEGF to promote rapid endothelialization on the intended vascular grafts, followed by a gradual but sustained release of heparin for long-term anticoagulation and antithrombogenicity. This method of forming a biologically responsive, multimodal delivery of VEGF and heparin is highly suitable for all hydrophobic surfaces and provides a promising way to meet the critical requirements of engineered small-diameter vascular grafts.

研究领域: 组织工程 · 生物材料 · 药物递送系统 · 血管外科
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Materials Science & Engineering C-Materials for Biological Applications · 2017 · IF 4.164

A facile way to prepare anti-fouling and blood-compatible polyethersulfone membrane via blending with heparin-mimicking polyurethanes

Chen Wang,Rui Wang,Yuan Xu,Man Zhang,Fan Yang,Shudong Sun,Changsheng Zhao

In this study, new kinds of heparin-mimicking polyurethanes (PUs) were fabricated conveniently in the mixed solution of dimethyl sulfoxide (DMSO) and water, reducing the usage of organic solvent. Functional groups of SO 3 H and/or COOH were introduced into PUs with various ratios of SO 3 H to COOH. The PUs were then blended with polyethersulfone (PES) to fabricate heparin-mimicking modified PES membranes by a phase inversion technique. Then, the microstructures, zeta potentials, water contact angles (WCA) and protein adsorptions of the membranes were characterized. Comparing with pristine PES membrane, the modified membranes showed changed cross-sectional morphology, lowered zeta potentials and decreased water contact angles, revealing that the hydrophilicity and anti-fouling properties were improved. The modified membranes also showed prolonged clotting tines (APTTs) and suppressed platelet adhesion, revealing that the anticoagulant properties increased. The results of complement activation, contact activation and platelet activation further implied that the modified membranes had good blood compatibility. In addition, the cells on the membranes showed good morphology with the introduction of the PUs. With the increase of the ratio of SO 3 H to COOH, the hydrophilicity, the blood compatibility as well as the cytocompatibility increased, implying that the SO 3 H groups could improve the hemocompatibility of the membranes more effectively than COOH groups. While the membranes containing more COOH groups had better antifouling properties of BSA and BFG. Therefore, the hemocompatibility for the heparin-mimicking membranes could be tuned by controlling the ratios of SO 3 H to COOH. The PES/PU composite membranes might have great potential to be used in the field of blood purification.

研究领域: 材料科学 · 生物医学工程 · 化学
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