Marine Drugs
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2022
·Vol. 20
·期 10
·654
·
IF 6.085
Pathum Chandika,Pipuni Tennakoon,Tae-Hee Kim,Se-Chang Kim,Jae-Young Je,Jae-Il Kim,Bonggi Lee,BoMi Ryu,Hyun Wook Kang,Hyun-Woo Kim,Young-Mog Kim,Chang Su Kim,Il-Whan Choi,Won Sun Park,Myunggi Yi,Won-Kyo Jung
Coagulation is a potential defense mechanism that involves activating a series of zymogens to convert soluble fibrinogen to insoluble fibrin clots to prevent bleeding and hemorrhagic complications. To prevent the extra formation and diffusion of clots, the counterbalance inhibitory mechanism is activated at levels of the coagulation pathway. Contrariwise, this system can evade normal control due to either inherited or acquired defects or aging which leads to unusual clots formation. The abnormal formations and deposition of excess fibrin trigger serious arterial and cardiovascular diseases. Although heparin and heparin-based anticoagulants are a widely prescribed class of anticoagulants, the clinical use of heparin has limitations due to the unpredictable anticoagulation, risk of bleeding, and other complications. Hence, significant interest has been established over the years to investigate alternative therapeutic anticoagulants from natural sources, especially from marine sources with good safety and potency due to their unique chemical structure and biological activity. This review summarizes the coagulation cascade and potential macromolecular anticoagulants derived from marine flora and fauna.Keywords:blood coagulation;anticoagulant;marine sources;marine anticoagulant macromolecules;chemically modified macromolecules
研究领域:
生物学
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医学
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DOI
PubMed
高影响因子
JOURNAL OF MEMBRANE SCIENCE
·
2014
·
IF 4.908
Hui Qin,Chuangchao Sun,Chao He,Dongsheng Wang,Chong Cheng,Shengqiang Nie,Shudong Sun,Changsheng Zhao
In this paper, we provide a highly efficient, convenient and universal protocol for blood-compatible modification of polyethersulfone (PES) membranes via in situ cross-linked copolymerization of 2-hydroxyethl methacrylate (HEMA) and acrylic acid (AA) in PES solutions. Static water contact angle, protein adsorption, platelet adhesion, and clotting time of the modified PES membranes are systematically studied, and the results indicate that the modified membranes show improved hydrophilicity, good blood anticoagulant and antifouling properties after introducing HEMA and AA. Meanwhile, the modified membranes perform low contact activation and complement activation when they come in contact with blood. The effect of the HEMA/AA ratios on the blood compatibility is also investigated to identify the different roles played by HEMA and AA in the modification; the HEMA could more effectively enhance the membrane antifouling property, while the AA could more effectively improve the anticoagulant property. The results indicated that the blood-compatible PES membranes prepared via the in situ cross-linked copolymerization had potential to be used in the field of blood purification.
研究领域:
材料科学
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生物医学工程
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产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2018
·
IF 3.909
Zhonghua Wang,Tongqiang Cai,Xipu He
Millettia dielsiana is a traditional herb medicine to treat rheumatic arthritis and gynecological diseases. In this study, a novel polysaccharide (MDP1) with a molecular weight of 139.54 kDa was isolated from Millettia dielsiana by DEAE-52 cellulose chromatography. Its sulfated derivative (S-MDP1) was prepared by the chlorosulfonic acid-pyridine method. Structural analysis indicated that MDP1 was a pectic polysaccharide and did not exhibit a triple helical conformation. In vitro , MDP1 and S-MDP1 had protective effect on H 2 O 2 -induced PC12 cells death. Immunological assay showed that MDP1 and S-MDP1 significantly stimulated NO production and phagocytic activity in RAW264.7 cells, and promoted lymphocyte proliferation . Anticoagulant assay indicated that S-MDP1 effectively prolonged activated partial thromboplastin time (APTT) and thrombin time (TT), but not prothrombin time (PT), and MDP1 prolonged APTT and TT weakly. These results implied that MDP1 and S-MDP1 had the potential to be used as antioxidant, immunomodulatory and anticoagulant agents.
研究领域:
药理学
·
生物化学
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DOI
PubMed
高影响因子
Bioactive Materials
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2025
·
IF 20.3
Zeyu Du,Yuting Huang,Qing Ma,Wentai Zhang,Yan Fu,Nan Huang,Xin Li,Zhilu Yang,Wenjie Tian
Surfaces with enduring and superior antithrombotic properties are essential for long-term blood-contacting devices. While current surface engineering strategies integrating anticoagulants and antiplatelet agents show promise in mimicking the non-thrombogenic properties of the endothelium, their long-term effectiveness remains limited. Here, we report an easy-to-perform, dual-biomimetic surface engineering strategy for tailoring long-acting endothelium-mimicking anti-thrombotic surfaces. We first designed a Mytilus edulis foot protein-5 (Mefp-5) mimic rich in amine and clickable alkynyl groups to polymerize-deposit a chemical robust coating onto the surface through a mussel-inspired adhesion mechanism. Then, a clickable nitric oxide (NO, an antiplatelet agent)-generating enzyme and the anticoagulant heparin were sequentially co-grafted onto the chemical robust coatings via click chemistry and carbodiimide chemistry. Our results demonstrate that this engineered surface achieved an impressive NO catalytic release efficiency of up to 88 %, while heparin retained 86 % of its bioactivity even after one month of exposure to PBS containing NO donor. Both in vitro and in vivo experiments confirmed that this robust endothelium-mimicking coating substantially reduces thrombosis formation. Overall, our long-acting endothelium-mimicking anti-thrombotic coatings present a promising and feasible strategy to address thrombosis-related challenges associated with blood-contacting devices.
研究领域:
生物材料学
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医学工程
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生物化学
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2024
·Vol. 12
·期 17
·4184-4196
·
IF 6.1
Linsen Li,Yue Yu,Xiaoqing Sun,Xingyou Wang,Xiayan Yang,Qifeng Yu,Ke Kang,Yao Wu,Qiangying Yi
Stent implantation is one of the most effective methods for the treatment of atherosclerosis. Nitinol stent is a type of stent with good biocompatibility and relatively mature development; however, it cannot effectively achieve long-term anticoagulation and early endothelialization. In this study, nitinol surfaces with the programmed assembly of heparin, exosomes from endothelial cells, and endothelial affinity peptide (REDV) were fabricated through layer-by-layer assembly technology and click-chemistry, and then exosomes/REDV-modified nitinol interface (ACC-Exo-REDV) was prepared. ACC-Exo-REDV could promote the rapid proliferation and adhesion of endothelial cells and achieve anticoagulant function in the blood. Besides, ACC-Exo-REDV had excellent anti-inflammatory properties and played a positive role in the transformation of macrophage from the pro-inflammatory to anti-inflammatory phenotype. Ex vivo and in vivo experiments demonstrated the effectiveness of ACC-Exo-REDV in preventing thrombosis and hyperplasia formation. Hence, the programmed assembly of exosome interface could contribute to endothelialization and have potential application on the cardiovascular surface modification to prevent stent thrombosis and restenosis.
研究领域:
生物医学工程
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心血管疾病
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材料科学
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产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2017
·Vol. 22
·期 12
·2047
·
IF 2.861
Xuan Luo,Chuanrong Du,Hui Cheng,Jian-hua Chen,Cuiwu Lin
In this study, three type II phenolic acids (caffeic acid,p-hydroxycinnamic acid, and ferulic acid) were used to synthesize a total of 18 phenolic acid derivatives. With molecular docking for molecule design and target protein (factors) screening, in combination with the confirmation of target proteins (factors) by surface plasmon resonance, and the evaluation of haemostatic and anticoagulant activities with five blood assays (plasma recalcification time, prothrombin time, activated partial thromboplastin time, fibrinogen, and thrombin time), the data indicated that caffeic acid derivatives showed certain anticoagulant or procoagulant activities and that two other series contained compounds with the best anticoagulant activities. Using Materials Studio analysis, particular functional groups that affect anticoagulant or procoagulant activities were revealed, and these conclusions can guide the discovery of compounds with better activities.Keywords:anticoagulant;procoagulant;haemostatic;phenolic acid;surface plasmon resonance
研究领域:
生物学
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医学
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药理学
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DOI
PubMed
高影响因子
Science of Advanced Materials
·
2020
·Vol. 12
·期 12
·1896-1906
·
IF 1.117
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
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医学工程
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生物医学
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DOI
高影响因子
Advanced Science
·
2024
·
IF 14.3
Wentai Zhang,Jiangling Zhang,Fangkun Hu,Wenxuan Wang,Zeyu Du,You Ke,Qing Ma,Xiaohui Mou,Jing Lu,Zhilu Yang
Universal protein coatings have recently gained wide interest in medical applications due to their biocompatibility and ease of fabrication. However, the challenge persists in protein activity preservation, significantly complicating the functional design of these coatings. Herein, an active dual-protein surface engineering strategy assisted by a facile stepwise protein–protein interactions assembly (SPPIA) method for catheters to reduce clot formation and infection is proposed. This strategy is realized first by the partial oxidation of bovine serum albumin (BSA) and lysozyme (LZM) for creating stable nucleation platforms via hydrophobic interaction, followed by the assembly of nonoxidized BSA (pI, the isoelectric point, ≈4.7) and LZM (pI ≈11) through electrostatic interaction owing to their opposite charge under neutral conditions. The SPPIA method effectively preserves the conformation and functionality of both BSA and LZM, thus endowing the resultant coating with potent antithrombotic and bactericidal properties. Furthermore, the stable nucleation platform ensures the adhesion and durability of the coating, resisting thrombosis and bacterial proliferation even after 15 days of PBS immersion. Overall, the SPPIA approach not only provides a new strategy for the fabrication of active protein coatings but also shows promise for the surface engineering technology of catheters.
研究领域:
生物医学工程
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材料科学
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表面工程
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产品关联
DOI
PubMed
高影响因子
BIOMACROMOLECULES
·
2024
·
IF 5.5
Biwei Qiu,Qianqian Cheng,Rukun Chen,Chunling Liu,Jinchao Qin,Qixia Jiang
Biodegradable stents are the most promising alternatives for the treatment of cardiovascular disease nowadays, and the strategy of preparing functional coatings on the surface is highly anticipated for addressing adverse effects such as in-stent restenosis and stent thrombosis. Yet, inadequate mechanical stability and biomultifunctionality limit their clinical application. In this study, we developed a multicross-linking hydrogel on the polylactic acid substrates by dip coating that boasts impressive antithrombotic ability, antibacterial capability, mechanical stability, and self-healing ability. Gelatin methacryloyl, carboxymethyl chitosan, and oxidized sodium alginate construct a double-cross-linking hydrogel through the dynamic Schiff base chemical and in situ blue initiation reaction. Inspired by the adhesion mechanism employed by mussels, a triple-cross-linked hydrogel is formed with the addition of tannic acid to increase the adhesion and antibiofouling properties. The strength and hydrophilicity of hydrogel coating are regulated by changing the composition ratio and cross-linking degree. It has been demonstrated in tests in vitro that the hydrogel coating significantly reduces the adhesion of proteins, MC3T3-E1 cells, platelets, and bacteria by 85% and minimizes the formation of blood clots. The hydrogel coating also exhibits excellent antimicrobial in vitro and antiinflammatory properties in vivo, indicating its potential value in vascular intervention and other biomedical fields.
研究领域:
生物医学工程
·
材料科学
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心血管医学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Xu Zhang,Mingzhe Wang,Lin Liu,Huan Yu,Yang Liu,Xiaozheng Duan,Lei Wang,Hengchong Shi,Shifang Luan
Interventional cardiovascular catheters (ICCs) are prone to complications such as venous thrombosis and occlusion during clinical applications, primarily due to the gradual adhesion and accumulation of cells, proteins, and microorganisms on their surfaces. Heparin sodium (HS) represents a typical clinically antithrombotic agent, whereas its hydrophilicity usually limits stable binding to hydrophobic catheter surfaces. Herein, we propose an easy-operating one-step strategy for fabricating hydrophobic-modified heparin based on electrostatic assembly between ethyl lauroyl arginate (ELA), a cationic antimicrobial compound, and anionic HS. The resulting ELA-HS complex shows water-insoluble and alcohol-soluble features, which can form a uniform and robust coating driven by electrostatic and hydrophobic interactions upon a series of catheters with diverse shapes and multi-cavity structures via solvent immersion. Molecular dynamics (MD) simulation elucidated the formation mechanism of hydrophobic-modified heparin, as well as the assembly mechanism between the coating and substrates. Importantly, this obtained ELA-HS coating with adaptive dissociation effectively resists the adsorption of fibrinogen and significantly reduces the adhesion of blood cells, including platelets, lymphocytes, and monocytes. Leveraging ELA’s inherent bactericidal properties, the coating also demonstrates substantial antibacterial efficacy, reducing bacterial colonization by over 99% whether gram-negative Escherichia coli ( E.coli. ) and gram-positive Staphylococcus aureus ( Sa. ). In vivo validation further confirms the coating’s dual functionality in preventing thrombosis and microbial infection, even in stringent acute models of canine jugular vein implantation. This ELA-HS modification strategy offers a practical solution to enhance the hemocompatibility and infection resistance of interventional catheters, addressing critical clinical challenges associated with thrombosis and bacterial adhesion.
研究领域:
生物医学工程
·
材料科学
·
心血管医学
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产品关联
DOI
高影响因子
International Journal of Polymer Science
·
2017
·
IF 1.077
Mei Han,Qiang Liu,Baihai Su,Shudong Sun,Changsheng Zhao
Polyurethanes (PUs) are currently considered to be biocompatible materials but limited by a low resistance to thrombus. We therefore design a heparin-like PU (HLPU) to modify polyethersulfone (PES) membranes approaching integrated antifouling and antithrombotic properties by bioinspiration of heparin structure. Poly(vinyl pyrrolidone)-HLPU (PVP-HLPU) was synthesized via reversible addition-fragmentation chain transfer polymerization of VP using PU as a macroinitiator and then sulfonated by concentrated H2SO4. FTIR and NMR results demonstrated the successful synthesis of PVP-HLPU. By incorporation of PVP-HLPU, the cross-sectional structure of PES composite membranes altered from finger-like structure to sponge-like structure resulting in tunable permeability. The increased hydrophilicity verified by water contact angles benefited both the permeability and antifouling property. As a consequence, the composite membranes showed good blood compatibility, including decreased protein adsorption, suppressed platelet adhesion, lowered thrombin-antithrombin III generation, reduced complement activation, and prolonged clotting times. Interestingly, the PVP-capped HLPU showed better blood compatibility compared to polyethyleneglycol-capped and citric acid-capped HLPUs. The results demonstrated the enhanced antifouling and antithrombotic properties of PES hemodialysis membranes by the introduction of functional HLPUs. Also, the proposed method may forward the fabrication of hemocompatible membranes via bioinspired surface design.
研究领域:
材料科学
·
生物医学工程
·
血液相容性研究
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DOI
高影响因子
ACS Biomaterials Science & Engineering
·
2024
·
IF 5.4
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
✓ 已验证
DOI
PubMed
高影响因子
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