ACS Applied Bio Materials
·
2025
·
IF 4.7
Xueyu Wang,Zhuojun Yan,Mengmeng Yao,Xiuqiang Li,Zhongming Zhao,Cheng Cao,Zhijie Zhao,Fanglian Yao,Yuping Wei,Hong Zhang,Junjie Li
Blood-contacting devices serve as a mainstay in clinical treatment, yet thrombosis remains a major cause of device failure and poses risks to patient health. In this study, we developed a diselenide cross-linker, N,N′-bis(methacryloyl)selenocystamine (BMASC), incorporated into poly(sulfobetaine methacrylate) (PSBMA) microgels (defined as BSM) to create an enzyme-mimetic zwitterionic microgel coating (BSMC). The superhydrophilicity of PSBMA provides outstanding antifouling performance, while the diselenide bonds mimic the catalytic action of glutathione peroxidase (GPx) in generating nitric oxide (NO). The microgels are covalently anchored to substrates pretreated with polydopamine (PDA) and polyethylenimine (PEI) through an epoxy-amine ring-opening reaction. During the drying process, the interpenetrating PSBMA chains of the microgels diffuse, forming a dense and smooth hydrogel coating. The BSMC exhibits exceptional resistance to nonspecific adhesion of proteins, cells, and bacteria, with the synergistic effects of antifouling properties and NO effectively inhibiting platelet adhesion. Furthermore, rabbit blood circulation experiments demonstrate the superior antithrombotic efficacy of the BSMC. This coating holds promise as an effective solution to address the thrombus formation challenges of blood-contacting devices.
研究领域:
生物材料
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医学工程
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药物化学
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产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2023
·
IF 8
Yuji Wang,Jingcheng Tang,Haimei Zhu,Xueyun Jiang,Jiawang Liu,Wenyun Xu,Haiping Ma,Qiqi Feng,Jianhui Wu,Ming Zhao,Shiqi Peng
The hot water extract of Rabdosia rubescens was traditionally used as an antithrombotic medicine. To explore its antithrombotic utility and mechanism, we carried out a series of in vitro and in vivo assays in this study. In vitro platelet aggregation assay showed that the half maximal inhibitory concentration values of aqueous extract of R. rubescens leaves (AERL) inhibiting platelet aggregation induced by thrombin, arachidonic acid, adenosine diphosphate, and platelet-activating factor ranged from 0.12 mg/mL to 1.43 mg/mL. The minimal effective oral dose of AERL inhibiting the rats from forming thrombus was 25 mg/kg. Both in vitro and in vivo actions were correlated with AERL concentration-dependently inhibiting sP-selectin release. In water, AERL formed nanoparticles, and their size depended on the concentration. Docking the five nucleotides, 21 phenolic acids, and four diterpenoids identified by high-performance liquid chromatography–photodiode array detector/(−)electrospray ionization-tandem mass spectrometry analysis into the active site of P-selectin, rosmarinic acid was predicted to be the antithrombotic ingredient of AERL. In flow cytometry analysis, 1 μM of rosmarinic acid effectively inhibited sP-selectin release in arachidonic acid-activated platelets. In a rat model, 5 mg/kg of oral rosmarinic acid effectively inhibited thrombosis.
研究领域:
药理学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
APPLIED SURFACE SCIENCE
·
2022
·
IF 7.392
Mingyu Li,Kunpeng Liu,Wenqi Liu,Nuoya Chen,Yanan Wang,Fanjun Zhang,Qingfeng Luo,Li Yang,Rifang Luo,Yunbing Wang
Blood-contacting devices, including vascular stents, catheters and extracorporeal membrane oxygenation (ECMO), often lead to complications such as thrombosis, inflammation and infections, resulting in implantation failure and adverse events in clinical applications. In this study, a facile and universal antifouling coating with superhydrophobic properties was proposed to improve the contacting interface for combating thrombosis and bacterial infections. The fabrication of the coating was based on Fenton reaction and silane coupling. Oxidative groups were introduced after Fenton activation and topological structure was constructed on the surface by silane coupling agents, and fluoride was used for modification. The obtained superhydrophobic coatings appeared as compact and uniform nanofibers that possessed good resistance to protein adsorption and platelet adhesion, while the thrombus formation was inhibited. In addition, the adhesion of Staphylococcus aureus and Escherichia coli was effectively prevented, which potentially delayed the formation of biofilm and reduced the risk of infections. The coating was applicable to a variety of substrates (polymer, non-metallic inorganic and metallic) and the superhydrophobic properties were preserved after immersion in PBS for 28 days, indicating that it was a promising antithrombotic and antibacterial candidate for modification of medical devices.
研究领域:
生物医学工程
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材料科学
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医学
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产品关联
DOI
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2025
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IF 5.4
Yu-Min Zhang,Qi Luo,Meng Lu,Xue Gong,Ya-Wei Guo,Xiang-Bin Zeng,Ying Zhu,Dan Shu,Yue-Ling Lin,Xu-Ran Guo,Zhang-Yin Ming
Ethnopharmacological relevance Ilex pubescens Hook. & Arn. is a traditional Chinese medicine for promoting blood circulation. Ilexsaponin A1 (IsA), a monomer of the compound, exhibits pro-angiogenic, anti-apoptotic and anti-inflammatory activities. Nevertheless, the pharmacological effects and specific mechanisms by which IsA affects platelets remain unknown. Aim of the study This study aims to investigate the antiplatelet effects of IsA and the underlying molecular mechanisms. Materials and methods Platelet aggregation and ATP release were assessed using platelet aggregometry. Flow cytometry was employed to evaluate the exposure of P-selectin, integrin α Ⅱb β 3 activation and calcium mobilization. Fluorescence microscopy was applied to observe platelet spreading. Clot retraction was imaged by digital camera. Protein phosphorylation regulation of major signaling pathways in platelets was determined by immunoblotting analysis. Doppler flowmetry was used to investigate the in vivo effect of IsA on FeCl 3 -induced carotid artery injury model. Tail vein transection was used to measure bleeding time. Results IsA dose-dependently inhibited platelet aggregation and ATP release induced by collagen, U46619, thrombin and ADP. It also suppressed thrombin-induced P-selectin exposure and PAC-1 binding. Furthermore, IsA inhibited intracellular Ca 2+ mobilization and the inward flow of extracellular Ca 2+ . It also influenced integrin α Ⅱb β 3 outside-in signaling pathways, including the inhibition of platelet spreading, clot retraction and phosphorylation of outside-in signaling molecules. In addition, IsA suppressed the phosphorylation of Syk-PLCγ2, PI3K-Akt-GSK3β and MAPKs proteins, which are downstream effectors of the collagen and thrombin receptors. Conclusion IsA inhibited platelet function and thrombus formation. This has potential to be developed into a novel therapeutic agent for the treatment of thrombotic diseases.
研究领域:
药理学
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分子生物学
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中药学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF SEPARATION SCIENCE
·
2025
·Vol. 48
·期 2
·e70090
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IF 2.8
Han Li,Xiaoming Wu,Yan Miao,Fengyu Dong,Xinjing Gui,Panpan Wang,Xuelin Li,Ruixin Liu
This study investigates the consistency of quality between the traditional decoction (TD) of Pheretima aspergillum and its dispensing granule decoction (DGD) by examining their chemical composition and antithrombotic efficacy. We first determined the nucleoside components, protein content, and volatile compounds in 10 batches of TD and 9 batches of DGD sourced from three manufacturers using high-performance liquid chromatography (HPLC), UV–vis spectrophotometry, and gas chromatography ion mobility spectrometry (GC-IMS). Next, we assessed antithrombotic efficacy by measuring the relative length of tail thrombosis and calculating the thrombus inhibition rates at 24 and 48 h. Our comprehensive analysis revealed that the concentrations of hypoxanthine, uridine, inosine, adenosine, and proteins in TD were significantly higher than those in DGD. Moreover, the types and concentrations of volatile compounds in TD and DGD exhibited substantial differences, with 19 volatile compounds identified as differentially present between the two decoctions. Despite these compositional differences, both decoction types demonstrated equivalent antithrombotic efficacy. Overall, the quality of DGD from manufacturers A and B aligned closely with that of TD. However, TD exhibited a higher overall quality compared to DGD, while both decoctions maintained consistent antithrombotic efficacy.
研究领域:
中药学
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药理学
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分析化学
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产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2019
·
IF 6.044
Lufeng Yan,Danli Wang,Mengshan Zhu,Yanlei Yu,Fuming Zhang,Xingqian Ye,Robert J. Linhardt,Shiguo Chen
Fucosylated chondroitin sulfate (FCS) oligosaccharides of specific molecular weight have shown potent anticoagulant activities with selectivity towards intrinsic factor Xase complex. However, the preparation of FCS oligosaccharides by traditional methods requires multiple purification steps consuming large amounts of time and significant resources. The current study focuses on developing a method for the rapid preparation of FCS oligomers from sea cucumber Pearsonothuria graeffei having 6–18 saccharide residues. The key steps controlling molecular weight ( M w) and purity of these FCS oligomers were evaluated. Structural analysis showed the resulting FCS oligomers were primarily l -Fuc3,4diS-α1,3- d -GlcA-β1,3-( d -GalNAc4,6diS-β1,4-[ l -Fuc3,4diS-α1,3-] d -GlcA-β1,3-) n d -anTal-ol4,6diS (n = 1˜5) accompanied by partial de-fucosylation and/or de-sulfation. In vitro and in vivo experiments demonstrate that these FCS oligomers selectively inhibit intrinsic factor Xase complex and exhibit remarkable antithrombotic activity without hemorrhagic and hypotension side effects. This method is suitable for large-scale preparation of FCS oligosaccharides as clinical anticoagulants.
研究领域:
生物化学
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药理学
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海洋生物学
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产品关联
DOI
PubMed
高影响因子
Nanomedicine-Nanotechnology Biology and Medicine
·
2022
·
IF 6.458
Yuanyuan Li,Yangye Jin,Xiaofeng He,Yonghui Tang,Min Zhou,Wenjing Guo,Wenjun Miao
The development of integrated nanomedicine for prevention and early diagnosis of thrombosis is highly significant. Platelet plays a vital role in thrombotic disorders, offering an ideal target for thromboprophylaxis and imaging of thrombi . We herein fabricated cyclo(RGD) peptide-decorated AgNPs (designated cRGD-AgNPs) for active targeting platelet-rich thrombi. In vitro cytotoxicity and hemolysis assays demonstrated that cRGD-AgNPs have acceptable biocompatibility pattern. Both PEG-AgNPs (non-targeted version) and cRGD-AgNPs can inhibit agonist-mediated platelet aggregation , whereas the latter exhibited significant attenuation on platelet activation and adhesion onto collagen and fibrinogen matrix. Furthermore, the superior binding ability of cRGD-AgNPs with platelet-rich thrombus was demonstrated in static/dynamic condition in vitro . In vivo studies revealed that cRGD-AgNPs could actively target thrombi in a mouse model of carotid artery thrombi with favorable safety. Our results here suggest that cRGD-AgNPs with intrinsic anti-platelet potential might be promising nano theranostics for thromboprophylaxis and active thrombus targeting.
研究领域:
纳米医学
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血液学
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生物材料
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产品关联
DOI
PubMed
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
·
2021
·
IF 7.328
Yuzhen Liao,Zhi Zhou,Sheng Dai,Lang Jiang,Ping Yang,Ansha Zhao,Lei Lu,Jiang Chen,Nan Huang
Titanium dioxide (TiO 2 ) is a widely used biomaterial. It is a great challenge to confer antibacterial and antithrombotic properties to TiO 2 while maintaining its cell affinity. Here, we developed a new strategy to achieve the above goal by comprehensively controlling the chemical cues and geometrical cues of the surface of TiO 2 . Using colloidal etching technology and UV irradiation treatment, we obtained the photofunctionalized nano-micro-honeycomb structured TiO 2 . The honeycomb structured increased the photocatalytic activity of TiO 2 , which endowed TiO 2 with photo-induced superhydrophilicity to inhibit bacterial adhesion. The high photocatalytic activity also induced the strong photocatalytic oxidation of TiO 2 surface organic adsorbates to suppress fibrinogen and platelet attachment. In addition, owing to the micropore trapping-isolation effect on the bacteria and the nano-frames' contact guidance effect on the growth and spreading of platelet pseudopods, the honeycomb structure also shows a considerable inhibiting effect on bacterial and platelet adhesion. Therefore, due to the controlled chemical and geometrical cues' synergistic effect, the photo-functionalized TiO 2 honeycomb structure shows excellent bacterial-adhesion resistance and antithrombotic properties. More importantly, the photo-functionalized TiO 2 honeycomb did not inhibit the adhesion and growth of endothelial cells (ECs) after culturing for 3 d, indicating a good cell affinity that the traditional antifouling surfaces do not possess.
研究领域:
生物材料学
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纳米技术
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表面科学
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DOI
PubMed
高影响因子
Pharmacognosy Magazine
·
2023
·
IF 0.7
Li Li,Wenfang Jin,Yue Wang,Li Yang,Zhi-Feng Zhang
BackgroundErigeron multiradiatus (Lindl.) Benth. has been used for years to treat various diseases in Traditional Tibetan Medicine (TTM). Our previous studies have shown that E. multiradiatus extract has important pharmacological effects, such as anti-myocardial ischemia–reperfusion (I/R) injury, anti-inflammatory, and anti-diabetic effects. To date, there have been no reports on using this extract to treat thrombosis.ObjectivesThe aim of this study was to enrich the active components of E. multiradiatus and to further investigate its anti-thrombotic activity.Materials and MethodsWe used D101 macroporous adsorption resin to enrich the main active substances of E. multiradiatus and performed quantitative determination using ultra-high-performance liquid chromatography with a photodiode array detector (UHPLC-PDA). Furthermore, we investigated the anti-thrombotic effects of E. multiradiatus using three models: an arachidonic acid-induced platelet aggregation thrombotic zebrafish model, a phenylhydrazine-induced red blood cell (RBC)-injuring thrombotic zebrafish model, and a ponatinib-induced vascular endothelial cell (VEC)-injuring thrombotic zebrafish model.ResultsThe yield of active component enrichment of E. multiradiatus was 4.95% using the D101 resin. We accurately determined eight compounds in the extract. Our results showed that these extracts had significant anti-thrombotic effects in the three different zebrafish models.ConclusionThe enriched extract of E. multiradiatus could be used as a natural anti-thrombotic agent. Our results will provide a reference for reasonable clinical applications of E. multiradiatus.
研究领域:
药理学
·
天然产物化学
✓ 已验证
产品关联
DOI
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
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IF 19
Jiayi Zhang,Yang Li,Zhen Xiang,Daihua Fu,Yunbing Wang
Cardiovascular stents persistently struggle to reconcile rapid endothelialization with long-term prevention of thrombosis and restenosis. This study develops a spatiotemporally orchestrated dual-gas-releasing hydrogel coating that synchronizes H 2 S and NO delivery with the dynamic phases of vascular healing. The coating is fabricated by covalently grafting an alginate coating onto poly(L-lactic acid) stents via a benzophenone-mediated two-step surface photopolymerization. A thiol‑activated H 2 S donor is anchored within the coating, while alginate‑chelated Cu 2 ⁺ catalyzes NO generation from endogenous S‑nitrosothiols. An early H 2 S burst synergizes with NO to suppress thromboinflammation and prime a regenerative niche, while sustained NO release maintains vascular homeostasis and directs long-term remodeling. The coating reduces platelet adhesion by over 90%, virtually eliminates thrombosis in an arteriovenous shunt model, triples endothelial coverage, and suppresses smooth muscle cell proliferation by ≈73%. It also reprograms macrophage polarization, increasing the M2/M1 ratio tenfold, and reduces intracellular ROS levels by >90%. In a rabbit abdominal aorta model, the coating promotes flow-aligned endothelialization, achieving CD31⁺/eNOS⁺ coverage comparable to native tissue within 3 months, while decreasing neointimal thickness by 66% versus controls. This spatiotemporally tailored gasotransmitter delivery resolves the healing dichotomy of stents, providing a clinically translatable platform for next-generation vascular implants.
研究领域:
生物材料学
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心血管医学
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再生医学
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纳米医学
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转化医学
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分子药理学
✓ 已验证
产品关联
DOI
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2017
·Vol. 27
·期 45
·1703934
·
IF 12.124
Cong Li,Hui Du,Aizhen Yang,Shuaibing Jiang,Zhenhua Li,Dan Li,John L. Brash,Hong Chen
Surface modification with bioactive agents capable of combating thrombosis is a widely used strategy for developing antithrombotic biomaterials. However, exposure of the blood to the antithrombotic agent on the material surface may cause hemostatic disorders under normal conditions. Ideally an implanted biomaterial should respond appropriately on demand to a specific change in the physiologic environment, as happens in the body itself. In the present study, a thrombosis-responsive surface coating with the ability to lyse fibrin as it forms is reported. The coating consists of nanocapsules (NCs) in which the fibrinolysis activator t-PA is encapsulated in a thrombin-degradable hydrogel shell. The t-PA NCs are attached to several materials covalently through a polydopamine adhesive layer. The resulting surfaces are treated with the antifouling agent glutathione (GSH) to prevent further interactions with blood/plasma components. The t-PA NCs/GSH-coated surface is stable and remain inert in normal plasma environment while releasing t-PA and promoting fibrinolysis when thrombin is present. The fibrinolytic activity increases with increasing thrombin concentration, and therefore presumably with the extent of thrombosis. This work constitutes the first report of an antithrombotic coating whose function is triggered and regulated, respectively, by the appearance of thrombin and the extent of coagulation.
研究领域:
生物材料
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医学工程
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血液学
✓ 已验证
产品关联
DOI
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2022
·
IF 5.999
Wenjing Guo,Yuanyuan Li,Daoguang An,Min Zhou,Jianming Xiong,Zhijun Jiang,Yimei Ding,Rongrong Huang,Wenjun Miao
Thrombosis is one of the feared complications contributing to death in patients with cardiovascular diseases. Ferulic acid (FA), a bioactive compound extracted from traditional Chinese medicines, has drawn tremendous attention in prevention and treatment of thrombosis because of its notable antithrombotic potency. However, the poor aqueous solubility and pharmacokinetic profile of FA limit its clinical use. In this study, sodium ferulate-functionalized silver nanopyramides (SF-pAgNPs) with narrow size distribution were synthesized to overcome these obstacles and enhance the suppression effect of platelet activation and thrombosis formation. The cytotoxicity and hemolysis assays demonstrated that the prepared nanopyramides have a favorable biocompatibility pattern. In vitro studies revealed that SF-pAgNPs could effectively suppress platelet activation, aggregation and adhesion through the synergetic antithrombotic potential of SF and nano silver. Furthermore, SF-pAgNPs exhibited potent antithrombotic activity and prolonged inhibitory effect, much better than PEG-Ag and free SF in mouse model. With enhanced antithrombotic effect and acceptable biocompatibility, we believe the sodium ferulate-functionalized silver nanopyramides might hold the potential to be a promising strategy for the prevention and treatment of thrombosis.
研究领域:
药理学
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纳米医学
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心血管疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）