Antithrombotic Surface Research Articles

Antithrombotic coating with sheltered positive charges prevents contact activation by controlling factor XII-biointerface binding.

Antithrombotic surfaces that prevent coagulation activation without interfering with haemostasis are required for blood-contacting devices. Such materials would restrain device-induced thrombogenesis and decrease the need for anticoagulant use, thereby reducing unwanted bleeding. Here, by optimizing the interactions with coagulation factor XII rather than preventing its surface adsorption, we develop a substrate-independent antithrombotic polymeric coating with sheltered positive charges. The antithrombic properties of the coating were demonstrated in vitro with human blood and in vivo using a carotid artery-jugular vein shunt model in rabbits. The coating exhibits a strong interaction with factor XII, but results in a low reciprocal activation of the contact pathway that triggers clot formation. These findings contradict the prevailing strategy of designing antithrombotic materials through protein-repelling surfaces. Overall, the polymeric coating we describe can benefit most blood-contacting devices and is a useful engineering guideline for designing surfaces with improved antithrombotic properties.

Lower-Ischemic-Risk Profile of Coated Flow Redirection Endoluminal Device X Compared With Uncoated Flow Redirection Endoluminal Device Flow Diverter in the Treatment of Unruptured Intracranial Aneurysms.

Flow Redirection Endoluminal Device (FRED) X is a new generation flow diverter with an antithrombotic surface coating. This study compares the procedural safety and short-term efficacy of FRED X with its uncoated predecessor, the FRED. Patients treated with FRED and FRED X devices for unruptured aneurysms between 2013 and 2023 at 3 neurovascular centers were retrospectively reviewed. The procedural ischemic event rate was the safety end point, and the complete aneurysm occlusion rate at 1 year was the efficacy end point. Multivariable regression adjustment and 1:1 propensity score matching were performed to control for potential confounding. The FRED X group (137 patients) had a higher prevalence of recurrent and bifurcation aneurysms and fewer aneurysms with branch involvement than the FRED X group (156 patients). The ischemic event rate was lower in FRED X (1/156 [0.6%]) than in FRED (7/137 [5.1%]), which was significant after multivariable adjustment (odds ratio: 8.8, 95% CI: 1.1-72.7, P = .04), and tended to be significant in the propensity score analysis (P = .07). Morbidity was comparable between FRED (2.2%) and FRED X (0%, P = .10). The complete occlusion rates of FRED vs FRED X were 73/117 (62.4%) vs 39/54 (72.2%) aneurysms at 6 months (P = .21) and 52/74 (70.3%) vs 27/37 (73.0%) at 12 months (P = .77). Hemorrhagic complications, in-stent stenosis, and clinical events during follow-up and retreatments were not significantly different between groups. This study indicates an improved ischemic risk profile of FRED X while maintaining a favorable efficacy profile, warranting further study and translation into clinical use.

Engineered endothelium-mimicking antithrombotic surfaces via combination of nitric oxide-generation with fibrinolysis strategies

Thrombosis associated with implants can severely impact therapeutic outcomes and lead to increased morbidity and mortality. Thus, developing blood-contacting materials with superior anticoagulant properties is essential to prevent and mitigate device-related thrombosis. Herein, we propose a novel single-molecule multi-functional strategy for creating blood-compatible surfaces. The synthesized azide-modified Cu-DOTA-(Lys)3 molecule, which possesses both NO release and fibrinolysis functions, was immobilized on material surfaces via click chemistry. Due to the specificity, rapidity, and completeness of click chemistry, the firmly grafted Cu-DOTA-(Lys)3 endows the modified material with excellent antithrombotic properties of vascular endothelium and thrombolytic properties of fibrinolytic system. This surface effectively prevented thrombus formation in both in vitro and in vivo experiments, owing to the synergistic effect of anticoagulation and thrombolysis. Moreover, the modified material maintained its functional efficacy after one month of PBS immersion, demonstrating excellent stability. Overall, this single-molecule multifunctional strategy may become a promising surface engineering technique for blood-contacting materials.

Evaluation of an Antithrombotic Surface-Coated Flow Diverter in a Rabbit Model without Dual Antiplatelet Drugs

OBJECTIVEFlow diverters (FDs) carry the risk of thromboembolic complications associated with the device and bleeding complications associated with dual antiplatelet therapy. We hypothesize that an antithrombotic surface coated flow diverter(BSCFD) would have less acute thrombus formation and better endothelialization on the device surface compared to uncoated flow diverter. METHODSAn antithrombotic surface coated FD(BSCFD) was developed. Acute clot formation and chronic endothelialization over the device were assessed in 8 rabbit models comparing to its prototype FD(PFD) at 2 hours and 1 month by Scanning Electron Microscopy(SEM) and Histologic images. Nonparametric score data, including thrombus, injury, endothelialization, adventitial inflammation, intramural bleeding and intimal hyperplasia were compared between BSCFD and PFD using Kendall coefficient of rank correlation. RESULTSParent artery and branch artery were patent on DSA in 8 BSCFDs and 6 PFDs. There was 1 intra-stent thrombosis in PFDs at 2 hours and 1 intra-stent stenosis in PFD at 1 month. SEM at 2 hours showed that large amount of blood cells adhered to the surface of all 4 PFDs, and no blood cells were found on the surface of all 4 BSCFDs. At SEM and histological analysis of 1 month, there were less inflammation(Kendall’s Tau-B=-0.818, p＝0.022), less vessel wall injury（Kendall’s Tau-B=-0.764, p＝0.032）and better endothelialization(Kendall’s Tau-B=0.818, p＝0.022) in BSCFDs. CONCLUSIONIn the rabbit model, the BSCFD is associated with less thrombus formation at acute stage, less inflammation, less vessel injury and better endothelialization on the device surface compared to the PFD.

FRED X flow diverter for the treatment of intracranial aneurysms: Two-center experience and mini-review of the literature.

The flow re-direction endoluminal device (FRED) is a safe and effective treatment option for intracranial aneurysms. The novel FRED X features an antithrombotic surface coating ("X Technology") on an otherwise unmodified stent design. This two-center study evaluates the clinical safety and efficacy of FRED X and compares it to the literature. Consecutive patients treated between 2020 and 2023 were retrospectively reviewed for aneurysm characteristics, procedural details and complications, and angiographic outcomes. A mini-review of the literature for FRED X clinical trials was performed and results were pooled using a random effects model. Thirty-four patients (mean age 56 years) were treated for 34 aneurysms. The mean aneurysm size was 7.7 ± 5.0 mm, 7 (21%) were ruptured, 6 (18%) were recurrent after previous treatment, 11 (32.3%) were located in the posterior circulation, and 4 (12.5%) had non-saccular morphology. All procedures were technically successful and no balloon angioplasty was required. There was 1 (2.9%) symptomatic complication (a transient ischemic attack) and no procedural morbidity or mortality. Technical asymptomatic events included 1 procedural stent occlusion that was reopened with thrombectomy and 3 cases of vasospasm. Complete and adequate occlusion rates were 68% (19/28) and 89% (25/28) at a mean follow-up time of 6 months, respectively. The results of this study are comparable to previous FRED X studies. The results demonstrate a high feasibility and procedural safety of the FRED X with adequate mid-term occlusion rates. Long-term and comparative studies are needed to evaluate the full potential of the FRED X.

Polyurethane with long hard segment for self-healing in blood environment around body temperature

Intravascular medical devices, like catheter, not only need to fulfill the challenge of biocompatibility but also be resistant to cracking or even breakage due to blood flushing and corrosion. Here, we synthesized polyurethanes with long hard segment for higher mechanical strength and effective self-healing in blood. In detail, Bis(trifluoromethyl)benzidine (TFMB) and dynamically linked 4-Aminophenyl disulfide (APS), and mixed diisocyanates of diisothiocyanate (PDITC) and hexamethylene diisocyanate (HMDI) were chosen to construct the long hard segment, which possesses hydrophobicity, dynamical bonds and a super strong hydrogen bonding interaction. For a selected sample, PU-4, which benefited from multi-hydrogen bonding, the degree of hydrogen bonding association kept as high as ∼ 97 % from 30 to 70 °C, and rheological testing proved that the hard domain and physical network are still stable at ∼ 115 °C. On the other hand, the surface content of Si is as high as 40 wt%, which not only endows the polymer with hydrophobicity but also a bioinert and antithrombotic surface. Consequently, the PU-4 showed a hemolysis rate of 0.4 %, an activated partial thromboplastin time of 50 s and free of platelet adhesion. By successfully screening complicate protein and ionic interactions with polymer chains, the self-healing of PU-4 in blood at 35 °C was realized, with mechanical strength recoverability up to 82 %.

Step-wise CAG@PLys@PDA-Cu2+ modification on micropatterned nanofibers for programmed endothelial healing.

Native-like endothelium regeneration is a prerequisite for material-guided small-diameter vascular regeneration. In this study, a novel strategy is proposed to achieve phase-adjusted endothelial healing by step-wise modification of parallel-microgroove-patterned (i.e., micropatterned) nanofibers with polydopamine-copper ion (PDA-Cu2+) complexes, polylysine (PLys) molecules, and Cys-Ala-Gly (CAG) peptides (CAG@PLys@PDA-Cu2+). Using electrospun poly(l-lactide-co-caprolactone) random nanofibers as the demonstrating biomaterial, step-wise modification of CAG@PLys@PDA-Cu2+ significantly enhanced substrate wettability and protein adsorption, exhibited an excellent antithrombotic surface and outstanding phase-adjusted capacity of endothelium regeneration involving cell adhesion, endothelial monolayer formation, and the regenerated endothelium maturation. Upon in vivo implantation for segmental replacement of rabbit carotid arteries, CAG@PLys@PDA-Cu2+ modified grafts (2mm inner diameter) with micropatterns on inner surface effectively accelerated native-like endothelium regeneration within 1 week, with less platelet aggregates and inflammatory response compared to those on non-modified grafts. Prolonged observations at 6- and 12-weeks post-implantation demonstrated a positive vascular remodeling with almost fully covered endothelium and mature smooth muscle layer in the modified vascular grafts, accompanied with well-organized extracellular matrix. By contrast, non-modified vascular grafts induced a disorganized tissue formation with a high risk of thrombogenesis. In summary, step-wise modification of CAG@PLys@PDA-Cu2+ on micropatterned nanofibers can significantly promote endothelial healing without inflicting thrombosis, thus confirming a novel strategy for developing functional vascular grafts or other blood-contacting materials/devices.

Risk factors for elective and emergency oxygenator exchanges during veno-venous extracorporeal membrane oxygenation.

Despite systemic anticoagulation and antithrombotic surface coating, oxygenator dysfunction remains one of most common technical complications of Extracorporeal membrane oxygenation (ECMO). Several parameters have been associated with an oxygenator exchange, but no guidelines for when to perform an exchange are published. An exchange, especially an emergency exchange, has a risk of complications. Therefore, a delicate balance between oxygenator dysfunction and the exchange of the oxygenator exists. This study aimed to identify risk factors and predictors for elective and emergency oxygenator exchanges. This observational cohort study included all adult patients supported with veno-venous extracorporeal membrane oxygenation (V-V ECMO). We compared patients' characteristics and laboratory values of patients with and without an oxygenator exchange and between an elective and emergency exchange, defined as an exchange outside office hours. Risk factors for an oxygenator exchange were identified with cox regression analyses, and risk factors for an emergency exchange were identified with logistic regression analyses. We included forty-five patients in the analyses. There were twenty-nine oxygenator exchanges in nineteen patients (42%). More than a third of the exchanges were emergency exchanges. Higher partial pressure of carbon dioxide (PaCO2), transmembrane pressure difference (ΔP), and hemoglobin (Hb) were associated with an oxygenator exchange. Lower lactate dehydrogenase (LDH) was the only risk factor for an emergency exchange. Oxygenator exchange is frequent during V-V ECMO support. PaCO2, ΔP and Hb were associated with an oxygenator exchange and lower LDH with the risk of an emergency exchange.

Development and In Vitro Whole Blood Hemocompatibility Screening of Endothelium-Mimetic Multifunctional Coatings.

Multifunctional antithrombotic surface modifications for blood-contacting medical devices have emerged as a solution for foreign surface-mediated coagulation disturbance. Herein, we have developed and evaluated an endothelium-inspired strategy to reduce the thrombogenicity of medical plastics by imparting nitric oxide (NO) elution and heparin immobilization on the material surface. This dual-action approach (NO+Hep) was applied to polyethylene terephthalate (PET) blood incubation vials and compared to isolated modifications. Vials were characterized to evaluate NO surface flux as well as heparin density and activity. Hemocompatibility was assessed in vitro using whole blood from human donors. Compared to unmodified surfaces, blood incubated in the NO+Hep vials exhibited reduced platelet aggregation (15% decrease AUC, p = 0.040) and prolonged plasma clotting times (aPTT = 147% increase, p < 0.0001, prothrombin time = 5% increase, p = 0.0002). Prolongation of thromboelastography reaction time and elevated antifactor Xa levels in blood from NO+Hep versus PET vials suggests some heparin leaching from the vial surface, confirmed by post-blood incubation heparin density assessment. Results suggest NO+Hep surface modification is a promising approach for blood-contacting plastics; however, careful tuning of NO flux and heparin stabilization are essential and require assessment using human blood as performed here.

Development of Novel Amphotericin B-Immobilized Nitric Oxide-Releasing Platform for the Prevention of Broad-Spectrum Infections and Thrombosis.

Indwelling medical devices currently used to diagnose, monitor, and treat patients invariably suffer from two common clinical complications: broad-spectrum infections and device-induced thrombosis. Currently, infections are managed through antibiotic or antifungal treatment, but the emergence of antibiotic resistance, the formation of recalcitrant biofilms, and difficulty identifying culprit pathogens have made treatment increasingly challenging. Additionally, systemic anticoagulation has been used to manage device-induced thrombosis, but subsequent life-threatening bleeding events associated with all available therapies necessitates alternative solutions. In this study, a broad-spectrum antimicrobial, antithrombotic surface combining the incorporation of the nitric oxide (NO) donor S-nitroso-N-acetylpenicillamine (SNAP) with the immobilization of the antifungal Amphotericin B (AmB) on polydimethylsiloxane (PDMS) was developed in a two-step process. This novel strategy combines the key advantages of NO, a bactericidal agent and platelet inhibitor, with AmB, a potent antifungal agent. We demonstrated that SNAP-AmB surfaces significantly reduced the viability of adhered Staphylococcus aureus (99.0 ± 0.2%), Escherichia coli (89.7 ± 1.0%), and Candida albicans (93.5 ± 4.2%) compared to controls after 24 h of in vitro exposure. Moreover, SNAP-AmB surfaces reduced the number of platelets adhered by 74.6 ± 3.9% compared to controls after 2 h of in vitro porcine plasma exposure. Finally, a cytotoxicity assay validated that the materials did not present any cytotoxic side effects toward human fibroblast cells. This novel approach is the first to combine antifungal surface functionalization with NO-releasing technology, providing a promising step toward reducing the rate of broad-spectrum infection and thrombosis associated with indwelling medical devices.

Combination strategies for antithrombotic biomaterials: an emerging trend towards hemocompatibility.

Surface-induced thrombosis is a frequent, critical issue for blood-contacting medical devices that poses a serious threat to patient safety and device functionality. Antithrombotic material design strategies including the immobilization of anticoagulants, alterations in surface chemistries and morphology, and the release of antithrombotic compounds have made great strides in the field with the ultimate goal of circumventing the need for systemic anticoagulation, but have yet to achieve the same hemocompatibility as the native endothelium. Given that the endothelium achieves this state through the use of many mechanisms of action, there is a rising trend in combining these established design strategies for improved antithrombotic actions. Here, we describe this emerging paradigm, highlighting the apparent advantages of multiple antithrombotic mechanisms of action and discussing the demonstrated potential of this new direction.

Preparation of phospholipid-based polycarbonate urethanes for potential applications of blood-contacting implants.

Polyurethanes are widely used in interventional devices due to the excellent physicochemical property. However, non-specific adhesion and severe inflammatory response of ordinary polyurethanes may lead to severe complications of intravenous devices. Herein, a novel phospholipid-based polycarbonate urethanes (PCUs) were developed via two-step solution polymerization by direct synthesis based on functional raw materials. Furthermore, PCUs were coated on biomedical metal sheets to construct biomimetic anti-fouling surface. The results of stress–strain curves exhibited excellent tensile properties of PCUs films. Differential scanning calorimetry results indicated that the microphase separation of such PCUs polymers could be well regulated by adjusting the formulation of chain extender, leading to different biological response. In vitro blood compatibility tests including bovine serum albumin adsorption, fibrinogen adsorption and denaturation, platelet adhesion and whole-blood experiment showed superior performance in inhibition non-specific adhesion of PCUs samples. Endothelial cells and smooth muscle cells culture tests further revealed a good anti-cell adhesion ability. Finally, animal experiments including ex vivo blood circulation and subcutaneous inflammation animal experiments indicated a strong ability in anti-thrombosis and histocompatibility. These results high light the strong anti-adhesion property of phospholipid-based PCUs films, which may be applied to the blood-contacting implants such as intravenous catheter or antithrombotic surface in the future.

Laser-induced wettability gradient surface on NiTi alloy for improved hemocompatibility and flow resistance.

Blood contacting materials with anti-thrombotic surfaces are highly demanded in clinics. Despite considerable research on surface modifications, limited progress has been made on effective prevention of thrombosis for artificial implants such as mechanical valve prosthesis. Herein, wettability gradient surface, which can ideally exhibit good hemocompatibility and low flow resistance, was developed for potential reduction of thrombosis. The wettability gradient surface on a model substrate of nickel-titanium (NiTi) alloy was prepared via a simple and economic method that combined laser microfabrication and surface stearic acid self-assembly approach. Scanning electron microscopy (SEM) observation confirmed that the wettability gradient surface was composed of a smooth NiTi region and three porous regions with different pore sizes and distances. Contact angle measurement revealed that, together with a low surface energy layer, the structural topography gradient could create a wettability gradient surface on NiTi alloy which could drive droplet motion. When compared with bare NiTi, such wettability gradient surface exhibited better anti-adhesion property, which was beneficial to the hemocompatibility and thus showing a lower hemolysis rate. Additionally, the wettability gradient surface also showed much lower flow resistance than bare NiTi. These results demonstrate that the developed wettability gradient surface may be used to reduce thrombosis.

Regenerating Antithrombotic Surfaces through Nucleic Acid Displacement

Blood-contacting devices are commonly coated with antithrombotic agents to prevent clot formation and to extend the lifespan of the device. However, in vivo degradation of these bioactive surface agents ultimately limits device efficacy and longevity. Here, a regenerative antithrombotic catheter surface treatment is developed using oligodeoxynucleotide (ODN) toehold exchange. ODN strands modified to carry antithrombotic payloads can inhibit the thrombin enzyme when bound to a surface and exchange with rapid kinetics over multiple cycles, even while carrying large payloads. The surface-bound ODNs inhibit thrombin activity to significantly reduce fibrinogen cleavage and fibrin formation, and this effect is sustained after ODN exchange of the surface-bound strands with a fresh antithrombotic payload. This study presents a unique strategy for achieving a continuous antithrombotic state for blood-contacting devices using an ODN-based regeneration method.

Active wrinkles to drive self-cleaning: A strategy for anti-thrombotic surfaces for vascular grafts

The inner surfaces of arteries and veins are naturally anti-thrombogenic, whereas synthetic materials placed in blood contact commonly experience thrombotic deposition that can lead to device failure or clinical complications. Presented here is a bioinspired strategy for self-cleaning anti-thrombotic surfaces using actuating surface topography. As a first test, wrinkled polydimethylsiloxane planar surfaces are constructed that can repeatedly transition between smooth and wrinkled states. When placed in contact with blood, these surfaces display markedly less platelet deposition than control samples. Second, for the specific application of prosthetic vascular grafts, the potential of using pulse pressure, i.e. the continual variation of blood pressure between systole and diastole, to drive topographic actuation was investigated. Soft cylindrical tubes with a luminal surface that transitioned between smooth and wrinkled states were constructed. Upon exposure to blood under continual pressure pulsation, these cylindrical tubes also showed reduced platelet deposition versus control samples under the same fluctuating pressure conditions. In both planar and cylindrical cases, significant reductions in thrombotic deposition were observed, even when the wrinkles had wavelengths of several tens of μm, far larger than individual platelets. We speculate that the observed thrombo-resistance behavior is attributable to a biofilm delamination process in which the bending energy within the biofilm overcomes interfacial adhesion. This novel strategy to reduce thrombotic deposition may be applicable to several types of medical devices placed into the circulatory system, particularly vascular grafts.

Microneedle Vascular Couplers with Heparin-Immobilized Surface Improve Suture-Free Anastomosis Performance.

To make up for the shortcomings of the suture-based approach and current coupler devices including long suturing time, exhaustive training, additional mechanical setting, and narrow working windows for size and type of diverse vessel types, a new, suture-free microneedle coupler was developed in this study. The needle shape for improved anastomosis performance and the condition for antithrombotic surface immobilization were determined. In particular, the polymer materials help to maintain healthy phenotypes of main vascular cell types. The performance in rabbit and porcine models of end-to-end vascular anastomosis indicate that this device can serve as a potent alternative to the current approaches.

Creating Rechargeable Antithrombotic Surfaces for Implantation via Enzyme-Mediated Ligation: A Novel System for Keeping Medical Devices Functional

Creating Rechargeable Antithrombotic Surfaces for Implantation via Enzyme-Mediated Ligation: A Novel System for Keeping Medical Devices Functional

Maintenance of Endothelial Cell Function in Liquid Based Antithrombotic Surface Coating

Preventing occurrence of thrombosis and biofouling is essential for safety and efficacy of an intravascular device. The slippery liquid-infused porous surface (SLIPS) technology has promise to achieve this goal by forming a liquidrepellent layer on the surface of blood contacting materials. As adhesion of biomolecules is greatly inhibited, the SLIPS-treated surface reduces thrombosing and biofouling. This study demonstrates that in static conditions, cells can adhere to SLIPS-treated surfaces without significant decreases in attachment or migration, as compared to untreated polymer surfaces. Furthermore, next generation RNA sequencing reveals that the SLIPS treatment does not change gene expression in endothelial cells (ECs). Taken together, our findings suggest that SLIPS treatment to be a biocompatible strategy that could potentially protect a variety of medical devices without compromising the process of endothelialization.

Point-of-Care Rapid-Seeding Ventricular Assist Device with Blood-Derived Endothelial Cells to Create a Living Antithrombotic Coating

The most promising alternatives to heart transplantation are left ventricular assist devices and artificial hearts; however, their use has been limited by thrombotic complications. To reduce these, sintered titanium (Ti) surfaces were developed, but thrombosis still occurs in approximately 7.5% of patients. We have invented a rapid-seeding technology to minimize the risk of thrombosis by rapid endothelialization of sintered Ti with human cord blood-derived endothelial cells (hCB-ECs). Human cord blood-derived endothelial cells were seeded within minutes onto sintered Ti and exposed to thrombosis-prone low fluid flow shear stresses. The hCB-ECs adhered and formed a confluent endothelial monolayer on sintered Ti. The exposure of sintered Ti to 4.4 dynes/cm for 20 hr immediately after rapid seeding resulted in approximately 70% cell adherence. The cell adherence was not significantly increased by additional ex vivo static culture of rapid-seeded sintered Ti before flow exposure. In addition, adherent hCB-ECs remained functional on sintered Ti, as indicated by flow-induced increase in nitric oxide secretion and reduction in platelet adhesion. After 15 day ex vivo static culture, the adherent hCB-ECs remained metabolically active, expressed endothelial cell functional marker thrombomodulin, and reduced platelet adhesion. In conclusion, our results demonstrate the feasibility of rapid-seeding sintered Ti with blood-derived hCB-ECs to generate a living antithrombotic surface.

Molecular Hemocompatibility of Graphene Oxide and Its Implication for Antithrombotic Applications.

Surface-induced blood clotting is one of the major problems associated with the long-term use of blood-contacting biomedical devices. Central to this obstructive blood clotting is the adsorption of plasma proteins following the interactions between blood and material surface. Of all proteins circulating in the blood plasma, albumin and fibrinogen are the two important proteins regulating the blood-material interaction. As such, the adsorption of plasma proteins has been used as an indicator for the assessment of the blood compatibility of the biomedical devices. Numerous nanomaterials have been developed for antithrombotic surface coating applications, including the 2D graphene and its derivatives. Here, the antithrombotic property of albumin-functionalized graphene oxide (albumin-GO) and its potential for antithrombotic coating application under flow are investigated. The loading capacities, conformational changes, and adsorptions of albumin and fibrinogen on GO are probed. It is observed that GO possesses a high loading capacity for both proteins and simultaneously, it does not disrupt the overall secondary structure and conformational stability of albumin. Both albumin and fibrinogen adsorb well on the surface of GO. Subsequently, it is demonstrated that the albumin-functionalized GO possesses enhanced antithrombotic effect and may potentially be used as an antithrombotic coating material of blood-contacting devices under dynamic flow.