Blood-contacting Devices Research Articles

Zwitterionic Polymers for Biomedical Applications: Antimicrobial and Antifouling Strategies toward Implantable Medical Devices and Drug Delivery.

Poly(ethylene glycol) (PEG) is extensively utilized in biomedical applications due to its biocompatibility; however, its thermal instability and susceptibility to oxidative degradation significantly constrain its long-term effectiveness. Zwitterionic polymers, characterized by their distinctive structure, enhanced stability, and superior biocompatibility, offer a more advantageous alternative. These polymers exhibit super hydrophilicity, resist nonspecific protein adsorption, and maintain stability in biological environments due to their charge-neutral ionic nature. Zwitterionic polymers enhance anticancer drug delivery by precisely targeting tumor cells and facilitating an efficient drug release. Their inherent antifouling properties and prolonged circulation within the bloodstream render them highly suitable for redox-sensitive drug carriers, thereby augmenting the antitumor efficacy. Moreover, zwitterionic polymers markedly mitigate biofouling in implants, biosensors, and wound dressings, thereby improving both their functionality and their therapeutic outcomes. These advantages arise from the formation of robust hydration layers, which significantly enhance the hemocompatibility and inhibit the adhesion of proteins, platelets, and bacteria. Zwitterionic polymers, including sulfobetaine (SB), phosphorylcholine (PC), and carboxybetaine (CB), are increasingly employed in blood-contacting devices and as effective coating materials for implantable devices. This mini-review paper aims to explore the recent diverse biomedical applications of zwitterionic polymers and highlight their advantageous properties compared with unmodified polymers. We will cover their use in drug delivery systems, tumor targeting nanocarriers, antibiofouling and antibacterial activities in implantable devices, tissue engineering, and diagnostic devices, demonstrating how their unique properties can translate into different applications. Through this exploration, this Perspective will display the potential of zwitterionic polymers as innovative polymer materials in the field of biomedical engineering and beyond.

Hemoincompatibility in Hemodialysis-Related Therapies and Their Health Economic Perspectives

Hemobiologic reactions associated with the hemoincompatibility of extracorporeal circuit material are an undesirable and inevitable consequence of all blood-contacting medical devices, typically considered only from a clinical perspective. In hemodialysis (HD), the blood of patients undergoes repetitive (at least thrice weekly for 4 h and lifelong) exposure to different polymeric materials that activate plasmatic pathways and blood cells. There is a general agreement that hemoincompatibility reactions, although unavoidable during extracorporeal therapies, are unphysiological contributors to non-hemodynamic dialysis-induced systemic stress and need to be curtailed. Strategies to lessen the periodic and direct effects of blood interacting with artificial surfaces to stimulate numerous biological pathways have focused mainly on the development of ‘more passive’ materials to decrease intradialytic morbidity. The indirect implications of this phenomenon, such as its impact on the overall delivery of care, have not been considered in detail. In this article, we explore, for the first time, the potential clinical and economic consequences of hemoincompatibility from a value-based healthcare (VBHC) perspective. As the fundamental tenet of VBHC is achieving the best clinical outcomes at the lowest cost, we examine the equation from the individual perspectives of the three key stakeholders of the dialysis care delivery processes: the patient, the provider, and the payer. For the patient, sub-optimal therapy caused by hemoincompatibility results in poor quality of life and various dialysis-associated conditions involving cost-impacting adjustments to lifestyles. For the provider, the decrease in income is attributed to factors such as an increase in workload and use of resources, dissatisfaction of the patient from the services provided, loss of reimbursement and direct revenue, or an increase in doctor–nurse turnover due to the complexity of managing care (nephrology encounters a chronic workforce shortage). The payer and healthcare system incur additional costs, e.g., increased hospitalization rates, including intensive care unit admissions, and increased medications and diagnostics to counteract adverse events and complications. Thus, hemoincompatibility reactions may be relevant from a socioeconomic perspective and may need to be addressed beyond just its clinical relevance to streamline the delivery of HD in terms of payability, future sustainability, and societal repercussions. Strategies to mitigate the economic impact and address the cost-effectiveness of the hemoincompatibility of extracorporeal kidney replacement therapy are proposed to conclude this comprehensive approach.

A superior material with antithrombotic properties serves as a secure adsorbent for the elimination of bilirubin in vitro and in pig models

Hyperbilirubinemia is primarily treated through hemoperfusion, a process that utilizes biomaterials as adsorbents to eliminate excessive bilirubin from the bloodstream. However, extracorporeal circuits are prone to thrombus formation due to the frequent use of blood-contacting devices, potentially leading to treatment failure and adverse clinical outcomes. In this study, using a resin substance treated with sulfated polysaccharides (GLU-ERM-0100), we present a reliable and safe approach for removing excessive bilirubin from blood. The resin’s pore size facilitates bilirubin adsorption, while sulfonic and hydroxyl groups incorporated within the material enable like-heparinization. GLU-ERM-0100 serves as a temporary blood-thinning agent, binding coagulation factors in the extracorporeal circuit, thereby eliminating the need for conventional anticoagulant medications. Both in vitro and animal studies demonstrate the material’s exceptional bilirubin adsorption capacity and effective anticoagulation properties.

Steps Toward Recapitulating Endothelium: A Perspective on the Next Generation of Hemocompatible Coatings.

Endothelium, the lining in this blood vessel, orchestrates three main critical functions such as protecting blood components, modulating of hemostasis by secreting various inhibitors, and directing clot digestion (fibrinolysis) by activating tissue plasminogen activator. No other surface can perform these tasks; thus, the contact of blood and blood-contacting medical devices inevitably leads to the activation of coagulation, often causing device failure, and thromboembolic complications. This perspective, first, discusses the biological mechanisms of activation of coagulation and highlights the efforts of advanced coatings to recapitulate one characteristic of endothelium, hereafter single functions of endothelium and noting necessity of the synergistic integration of its three main functions. Subsequently, it is emphasized that to overcome the challenges of blood compatibility an endothelium-mimicking system is needed, proposing a synergy of bottom-up synthetic biology, particularly synthetic cells, with passive- and bioactive surface coatings. Such integration holds promise for developing advanced biomaterials capable of recapitulating endothelial functions, thereby enhancing the hemocompatibility and performance of blood-contacting medical devices.

The influence of non-Newtonian behaviors of blood on the hemodynamics past a bileaflet mechanical heart valve

This study employs extensive three-dimensional direct numerical simulations to investigate the hemodynamics around a bileaflet mechanical heart valve. In particular, this study focuses on assessing whether non-Newtonian rheological behaviors of blood, such as shear-thinning and yield stress behaviors, exert an influence on hemodynamics compared to the simplistic Newtonian behavior under both steady inflow and physiologically realistic pulsatile flow conditions. Under steady inflow conditions, the study reveals that blood rheology impacts velocity and pressure field variations, as well as the values of clinically important surface and time-averaged parameters like wall shear stress (WSS) and pressure recovery. Notably, this influence is most pronounced at low Reynolds numbers, gradually diminishing as the Reynolds number increases. For instance, surface-averaged WSS values obtained with the non-Newtonian shear-thinning power-law model exceed those obtained with the Newtonian model. At Re=750, this difference reaches around 67%, reducing to less than 1% at Re=5000. Correspondingly, pressure recovery downstream of the valve leaflets is lower for the shear-thinning blood than the constant viscosity one, with the difference decreasing as the Reynolds number increases. On the other hand, in pulsatile flow conditions, jets formed between the leaflets and the valve housing wall are shorter than steady inflow conditions. Additionally, surface-averaged wall shear stress and blood damage (BD) parameter values are higher (with differences more than 13% and 47%, respectively) during the peak stage of the cardiac cycle, especially for blood exhibiting non-Newtonian yield stress characteristics compared to the shear-thinning or constant viscosity characteristics. Therefore, blood non-Newtonian behaviors, including shear-thinning and yield stress behaviors, exert a considerable influence on the hemodynamics around a mechanical heart valve. All in all, the findings of this study demonstrate the importance of considering non-Newtonian blood behaviors when designing blood-contacting medical devices, such as mechanical heart valves, to enhance functionality and performance.

Aggregation-Disruption-Induced Multi-Scale Mediating Strategy for Anticoagulation in Blood-Contacting Devices.

Minimally invasive blood-contacting interventional devices are increasingly used to treat cardiovascular diseases. However, the risk of device-related thrombosis remains a significant concern, particularly the formation of cycling thrombi, which pose life-threatening risks. To better understand the interactions between these devices and blood, the initial stages of coagulation contact activation on extrinsic surfaces areinvestigated. Direct force measurements reveals that activated contact factors stimulate the intrinsic coagulation pathway and promote surface crosslinking of fibrin. Furthermore, fibrin aggregation is disrupted by surface-grafted inhibitors, as confirmed by ex vivo coagulation tests. An engineered serum protein with zwitterion grafts to resist the deposition of biological species such as fibrin, platelets, and red blood cells is also developed. Simultaneously, a protease inhibitor-based coacervate is incorporated into the coating to inhibit the intrinsic pathway effectively. The loaded coacervate can be released and reloaded through modulation of catechol-amine interactions, facilitating material regeneration. The strategy offers a novel multi-scale mediation strategy that simultaneously inhibits nanoscale coagulation factors and resists microscale thrombus aggregation, providing a long-term solution for anticoagulation in blood-contacting devices.

Differences in human and commercial hybrid pig platelet activation induced by borosilicate glass beads in a modified chandler loop-system.

The pig (Sus scrofa) is the most widely used large animal model in Europe, with cardiovascular research being one of the main areas of application. Adequate refinement of interventional studies in this field, meeting the requirements of Russell and Burch's 3 R concept, can only be performed if blood-contacting medical devices are hemocompatible. Because most medical devices for cardiovascular interventional procedures are developed for humans, they are tested only for compatibility with human blood. The aim of this study was therefore to determine whether there are differences in behavior of human and porcine platelets from commercial hybrid pigs when they come into contact with borosilicate glass, which was used as an exemplary thrombogenic material. For this purpose, changes in platelet count, platelet volume and platelet expression of the activation markers CD61, CD62P and CD63 were measured using a modified chandler loop-system simulating the fluidic effects of the bloodflow. Commercial hybrid pig and human platelets showed significant adhesions to borosilicate glass but the commercial hybrid pigs platelets showed a significantly higher tendency to adhere to borosilicate glass. In contrast to human platelets the platelets of commercial hybrid pigs showed significant activation after 4 to 8 minutes exposure to borosilicate glass and there were differences among the ratios of surface and activation markers in between the platelets of both species.

Computational fluid dynamics simulating of the FDA benchmark blood pump with different coefficient sets and scaler shear stress models used in the power-law hemolysis model.

Hemolysis is the most important issue to consider in the design and optimization of blood-contacting devices. Although the use of Computational Fluid Dynamics (CFD) in hemolysis prediction studies provides convenience and has promising potential, it is an extremely challenging process. Hemolysis predictions with CFD depend on the mesh, implementation method, coefficient set, and scalar-shear-stress model. To this end, an attempt was made to find the combination that would provide the most accurate result in hemolysis prediction with the commonly cited power-law based hemolysis model. In the hemolysis predictions conducted using CFD on the Food and Drug Administration (FDA) benchmark blood pump, 3 different scalar-shear-stress models, and 5 different coefficient sets with the power-law based hemolysis model were used. Also, a mesh independence test based on hemolysis and pressure head was performed. The pressure head results of CFD simulations were compared with published pressure head of the FDA benchmark blood pump and a good agreement was observed. In addition, results of CFD-hemolysis predictions which are conducted with scalar-shear-stress model and coefficient set combinations were compared with experimental hemolysis data at three operating conditions such as 6-7L/min flow rates at 3500rpm rotational speeds and 6L/min at 2500rpm. One of the combinations of the scalar-shear-stress model and the coefficient set was found to be within the error limits of the experimental measurements, while all other combinations overestimated hemolysis.

Preparation of Time-Sequential Functionalized ZnS-ZnO Film for Modulation of Interfacial Behavior of Metals in Biological Service Environments.

Blood-contact devices are prone to inflammation, endothelial dysfunction, coagulation, and the uncontrolled release of metal ions during implantation and service. Therefore, it is essential to make these multifunctional. Herein, a superhydrophobic DE@ZnS-ZnO@SA film (composed of dabigatran ester, zinc sulfite, zinc oxide, and stearic acid, respectively) is produced. The prepared film has non-adhesion and antibacterial properties, superior mechanical stability, durability, corrosion resistance, and is self-cleaning and blood-repellent. The results of the hemolysis, cytotoxicity, and other anticoagulant experiments revealed that the film had good blood compatibility, no cytotoxicity, and excellent anticoagulant properties. The film displays anticoagulant properties even after being immersed in Phosphate-Buffered Saline (PBS) for 7 days. Furthermore, the film can spontaneously release H2S gas for 90 h after soaking in an acidic environment (pH = 6) for 90 h. This property improves the acidic microenvironment of the lesion and promotes the proliferation of endothelial cells by using H2S gas. In addition, the film can inhibit the uncontrollable release of Zn2+ ions, avoiding its toxicity even when immersed in an acid environment for 35 days. This time-sequential functionalized surface has the potential to typify the future of blood-contacting scaffolds for long-lasting use.

Characterizing thrombus adhesion strength on common cardiovascular device materials.

Thrombus formation in blood-contacting medical devices is a major concern in the medical device industry, limiting the clinical efficacy of these devices. Further, a locally formed clot within the device has the potential to detach from the surface, posing a risk of embolization. Clot embolization from blood-contacting cardiovascular devices can result in serious complications like acute ischemic stroke and myocardial infarction. Therefore, clot embolization associated with device-induced thrombosis can be life-threatening and requires an enhanced fundamental understanding of embolization characteristics to come up with advanced intervention strategies. Therefore, this work aims to investigate the adhesive characteristics of blood clots on common biocompatible materials used in various cardiovascular devices. This study focuses on characterizing the adhesion strength of blood clots on materials such as polytetrafluoroethylene (PTFE), polyurethane (PU), polyether ether ketone (PEEK), nitinol, and titanium, frequently used in medical devices. In addition, the effect of incubation time on clot adhesion is explored. Results from this work demonstrated strongest clot adhesion to titanium with 3h of incubation resulting in 1.06 ± 0.20kPa detachment stresses. The clot adhesion strength on titanium was 51.5% higher than PEEK, 35.9% higher than PTFE, 63.1% higher than PU, and 35.4% higher than nitinol. Further, adhesion strength increases with incubation time for all materials. The percentage increase in detachment stress over incubation time (ranging from 30min to 3h) for polymers ranged from at least 108.75% (PEEK), 140.74% (PU), to 151.61% (PTFE). Whereas, for metallic surfaces, the percentage rise ranged from 70.21% (nitinol) to 89.28% (titanium). Confocal fluorescence imaging of clot remnants on the material surfaces revealed a well-bounded platelet-fibrin network at the residual region, representing a comparatively higher adhesive region than the non-residual zone of the surface.

Simulation of the effect of hemolysis on thrombosis in blood-contacting medical devices

Heart failure, broadly characterized by the gradual decline of the ability of the heart to maintain adequate blood flow throughout the body's vascular network of veins and arteries, is one of the leading causes of death worldwide. Mechanical Circulatory Support is one of the few available alternative interventions for late-stage heart failure with reduced ejection fraction. A ventricular assist device is surgically implanted and connected to the left and or right heart ventricles to provide additional bloodflow, off-loading the work required by the heart to maintain circulation. Modern mechanical circulatory support devices generate non-physiological flow conditions that can lead to the damage and rupture of blood cells (hemolysis), and the formation of blood clots (thrombosis), which pose severe health risks to the patient. It is essential to improve prediction tools for blood damage to reduce the risk of hemolysis and thrombosis. A simulation-based approach examines the interaction between hemolysis and thrombosis. Incompressible finite-volume computational fluid dynamics simulations are executed on an open-hub axial flow ventricular assist device. A continuum model of thrombosis and the intrinsic coagulation process is extended to include the effect of hemolysis. The model accounts for the effect of activation of platelets by shear stress, paracrine signaling, adhesion, and hemoglobin and ADP released during hemolysis. The effect of hemolysis with thrombosis is modelled by accounting for the hyper-adhesivity of von-Willebrand Factor on extracellular hemoglobin, and the increased rate of platelet activation induced by ADP release. Thrombosis is assessed at varying inflow rates and rotor speeds, and cases are executed where thrombosis is affected by ADP release and Hb-induced hyper-adhesivity. It is found that there is a non-negligible effect from hemolysis on thrombosis across a range of rotor speeds, and that hyperadhesivity plays a dominant role in thrombus formation in the presence of hemolysis.

Platelet Adhesion and Activation in an ECMO Thrombosis-on-a-Chip Model.

Use of extracorporeal membrane oxygenation (ECMO) for cardiorespiratory failure remains complicated by blood clot formation (thrombosis), triggered by biomaterial surfaces and flow conditions. Thrombosis may result in ECMO circuit changes, cause red blood cell hemolysis, and thromboembolic events. Medical device thrombosis is potentiated by the interplay between biomaterial properties, hemodynamic flow conditions and patient pathology, however, the contribution and importance of these factors are poorly understood because many in vitro models lack the capability to customize material and flow conditions to investigate thrombosis under clinically relevant medical device conditions. Therefore, an ECMO thrombosis-on-a-chip model is developed that enables highly customizable biomaterial and flow combinations to evaluate ECMO thrombosis in real-time with low blood volume. It is observed that low flow rates, decelerating conditions, and flow stasis significantly increased platelet adhesion, correlating with clinical thrombus formation. For the first time, it is found that tubing material, polyvinyl chloride, caused increased platelet P-selectin activation compared to connector material, polycarbonate. This ECMO thrombosis-on-a-chip model can be used to guide ECMO operation, inform medical device design, investigate embolism, occlusion and platelet activation mechanisms, and develop anti-thrombotic biomaterials to ultimately reduce medical device thrombosis, anti-thrombotic drug use and therefore bleeding complications, leading to safer blood-contacting medical devices.

Fabrication of metal-organic frameworks containing Cu2+ coated medical PVC catheters with durable antiplatelet and antibacterial activities

Polyvinyl chloride (PVC) catheters are widely used in medical environments especially in blood-contacting devices. In this study, a copper containing MOF material was coated on a PVC catheter to endow it with antiplatelet adhesion and antibacterial activity for potential clinical applications. The immobilization of the coordination polymer containing Cu2+ (Cu-MOF) on the inner surface of PVC catheters was carried out using a bioinspired coating combined with a layer-by-layer self-assembly strategy. Characterization of the Cu-MOF modified surfaces was confirmed using micro-infrared spectroscopy (MIR), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), and water contact angle measurements (WCA). The resultant modified surfaces significantly reduced non-specific adsorption to model proteins with excellent anti-biofouling activity, as well as significantly inhibited the platelet adhesion and activation with superior antiplatelet activity. In vitro whole blood circulation test using a peristaltic pump also showed good antithrombotic properties. Besides, the Cu-MOF modified surfaces exhibited good hemocompatibility (hemolysis ratio < 5 %) and excellent antibacterial activity (approximately 97 % against S. auerus and E. coli). This study develops a simple and effective method for the surface modification of medical PVC catheter as potential blood-contacting biomaterials.

Zwitterionic modification: A strategy to enhance the mechanical properties, lubricity and hemo- and biocompatibility of silicone poly(carbonate urethane urea)

Incorporating zwitterions into the blood-contacting materials has been demon-strated an effective and convenient strategy to minimize protein adsorption and platelet deposition, but is frequently detrimental to the mechanical properties. Herein a feeding 29.0 mol% sulfobetaine (SB) siloxane poly(carbonate urethane urea) (SSiPCUU) was synthesized and evaluated. Although the equilibrium water uptake ratio was increased to 1.20% markedly depressing the hydrolytic degradation resistance and mechanical properties after the zwitterionic modification, its maximum tensile stress and tear strength in the wet state still kept the highest among all the tested samples because the urea groups created therefrom gave rise to the formation of bifurcating hydrogen bonds making a significant contribution to the mechanical properties alongside the unique ion clusters formed from pendant SB species. As a consequence of zwitterionic incorporation, it exhibited an extremely low friction coefficient indicating an excellent lubricity in a wet environment without any post-treatment. Accordingly, both the nonspecific protein adsorption and platelet adhesion were evidently decreased. Moreover, it also depicted a good transparency. The high lubrication performance is desirable for lessening the damage to human blood vessels and a good transparency is favorable to the visualization of the flow of liquid in the catheter. These results illustrated the great potential of the zwitterionic SSiPCUU used in the preparation of balloon catheters, artificial blood vessels, stent coverings and other blood-contacting medical implants and devices.

Empirical and Computational Evaluation of Hemolysis in a Microfluidic Extracorporeal Membrane Oxygenator Prototype.

Microfluidic devices promise to overcome the limitations of conventional hemodialysis and oxygenation technologies by incorporating novel membranes with ultra-high permeability into portable devices with low blood volume. However, the characteristically small dimensions of these devices contribute to both non-physiologic shear that could damage blood components and laminar flow that inhibits transport. While many studies have been performed to empirically and computationally study hemolysis in medical devices, such as valves and blood pumps, little is known about blood damage in microfluidic devices. In this study, four variants of a representative microfluidic membrane-based oxygenator and two controls (positive and negative) are introduced, and computational models are used to predict hemolysis. The simulations were performed in ANSYS Fluent for nine shear stress-based parameter sets for the power law hemolysis model. We found that three of the nine tested parameters overpredict (5 to 10×) hemolysis compared to empirical experiments. However, three parameter sets demonstrated higher predictive accuracy for hemolysis values in devices characterized by low shear conditions, while another three parameter sets exhibited better performance for devices operating under higher shear conditions. Empirical testing of the devices in a recirculating loop revealed levels of hemolysis significantly lower (<2 ppm) than the hemolysis ranges observed in conventional oxygenators (>10 ppm). Evaluating the model's ability to predict hemolysis across diverse shearing conditions, both through empirical experiments and computational validation, will provide valuable insights for future micro ECMO device development by directly relating geometric and shear stress with hemolysis levels. We propose that, with an informed selection of hemolysis parameters based on the shear ranges of the test device, computational modeling can complement empirical testing in the development of novel high-flow blood-contacting microfluidic devices, allowing for a more efficient iterative design process. Furthermore, the low device-induced hemolysis measured in our study at physiologically relevant flow rates is promising for the future development of microfluidic oxygenators and dialyzers.

Insights into the writing process of the mask-free nanoprinting fluid force microscopy technology

Platelets are activated immediately when contacting with non-physiological surfaces. Minimization of surface-induced platelet activation is important not only for platelet storage but also for other blood-contacting devices and implants. Chemical surface modification tunes the response of cells to contacting surfaces, but it requires a long process involving many regulatory challenges to transfer into a marketable product. Biophysical modification overcomes these limitations by modifying only the surface topography of already approved materials. The available large and random structures on platelet storage bags do not cause a significant impact on platelets because of their smallest size (only 1–3 μm) compared to other cells. We have recently demonstrated the feasibility of the mask-free nanoprint fluid force microscope (FluidFM) technology for writing dot-grid and hexanol structures. Here, we demonstrated that the technique allows the fabrication of nanostructures of varying features including grid, circle, triangle, and Pacman-like structures. Characteristics of nanostructures including height, width, and cross-line were analyzed and compared using atomic force microscopy imaging. Based on the results, we identified several technical issues, such as the printing direction and shape of structures that directly altered nanofeatures during printing. Importantly, both geometry and interspace governed the degree of platelet adhesion, especially, the structures with triangular shapes and small interspaces prevent platelet adhesion better than others. We confirmed that FluidFM is a powerful technique to precisely fabricate a variety of desired nanostructures for the development of platelet/blood-contacting devices if technical issues during printing are well controlled.

Transient Performance Analysis of Centrifugal Left Ventricular Assist Devices Coupled With Windkessel Model: Large Eddy Simulations Study on Continuous and Pulsatile Flow Operation.

Computational fluid dynamics (CFD) simulations are widely used to develop and analyze blood-contacting medical devices such as left ventricular assist devices (LVADs). This work presents an analysis of the transient behavior of two centrifugal LVADs with different designs: HeartWare VAD and HeartMate3. A scale-resolving methodology is followed through Large Eddy Simulations, which allows for the visualization of turbulent structures. The three-dimensional (3D) LVAD models are coupled to a zero-dimensional (0D) 2-element Windkessel model, which accounts for the vascular resistance and compliance of the arterial system downstream of the device. Furthermore, both continuous- and pulsatile-flow operation modes are analyzed. For the pulsatile conditions, the artificial pulse of HeartMate3 is imposed, leading to a larger variation of performance variables in HeartWare VAD than in HeartMate3. Moreover, CFD results of pulsatile-flow simulations are compared to those obtained by accessing the quasi-steady maps of the pumps. The quasi-steady approach is a predictive tool used to provide a preliminary approximation of the pulsatile evolution of flow rate, pressure head, and power, by only imposing a speed pulse and vascular parameters. This preliminary quasi-steady solution can be useful for deciding the characteristics of the pulsatile speed law before running a transient CFD simulation, as the former entails a significant reduction in computational cost in comparison to the latter.

Green waterborne synthesis of hemocompatible polycarbonate–polyether polyurethanes

Polyurethane (PU) is a family of biomedical elastomers with promising applications. In this study, we describe the synthesis of a novel waterborne PU with high solid content and low viscosity. The soft segment of the PU consists of polycarbonate diol (PCDL) and polytetramethylene ether glycol. Dimethylolbutanoic acid is used as a chain extender. To stabilize the emulsion in the synthetic process, nonionic groups (polyoxyethylene styrenated phenyl and polyoxyethylene tridecyl ethers) are used as surfactants. PUs with good hydrophilicity and proper hemocompatibility were successfully synthesized using this approach. The chemical composition of the PU was adjusted by changing the soft-to-hard segment ratio. The effects of this composition ratio on the crystallization properties of PU were characterized using differential scanning calorimetry, X-ray diffraction, scanning electron microscopy, transmission electron microscopy, attenuated total reflectance infrared spectroscopy, thermogravimetric analysis, alternating magnetic field, and contact angle measurements. Film casts from PUs prepared in this study showed good mechanical properties, including Young’s modulus (0.66–48 MPa), tensile strength (11.7–30.9 MPa), and strain at break (173%–579%). Moreover, introducing PCDL in the soft segment during preparation improved the microphase separation and reduced the water contact angle of the films, which enhanced the hydrophilicity of the PU. Our findings demonstrate the potential of the new waterborne PU formulation to significantly improve the performance and durability of biomaterials and blood-contacting devices. Furthermore, this formulation meets the required hemolytic standards, which supports its suitability for medical applications.

Surface nanostructuring of Ti40Cu40Zr11Fe3Sn3Ag3 amorphous alloy by alkaline chemical treatment for potential use as a biocompatible material

Amorphous alloys show potential as implant materials due to their superior mechanical properties and good corrosion resistance. However, the presence of toxic elements in the alloy composition can pose challenges, as they can react with the surrounding tissue, leading to inflammation and cell death. To address this, Ti40Cu40Zr11Fe3Sn3Ag3 at% amorphous alloy is developed. This composition comprises of biocompatible elements (Ti, Zr, and Sn) and antimicrobial elements (Ag, Fe, and Cu), for potential use as implant materials. Chemical pseudo-dealloying using a solution of ammonium hydroxide and hydrogen peroxide is employed to selectively remove copper from the sample surface, which may induce toxicity by prolonged contact, and promote the formation of a patterned passivating Ti/Zr oxide-rich surface to enable possible antimicrobial effects. The surface of the samples was analyzed using atomic force microscopy, scanning electron microscopy, and X-ray photoelectron spectroscopy. The modified surfaces show titanium oxide-rich nanostructured topography with depleted amounts of copper from the surface. The kinetics of the selective removal of copper, and the influence of parameters such as electrolyte concentration, immersion time, and stirring velocity on the evolution of morphology were investigated. Our findings elucidate the mechanism of pseudo-dealloying using an ammonia-based solution and demonstrate its efficacy in enhancing the biocompatibility of the alloy. In detail, the pseudo-dealloyed samples exhibited hydrophilic interactions and demonstrated hemocompatibility, making them promising candidates for blood-contacting medical devices. This study underscores the significance of our approach in tailoring the surface properties of amorphous alloys for biomedical applications, paving the way for their utilization in implant materials with improved biocompatibility.

In vivo assessment of dual-function submicron textured nitric oxide releasing catheters in a 7-day rabbit model

Catheter-induced thrombosis is a major contributor to infectious and mechanical complications of biomaterials that lead to device failure. Herein, a dualfunction submicron textured nitric oxide (NO)-releasing catheter was developed. The hemocompatibility and antithrombotic activity of vascular catheters were evaluated in both 20 h in vitro blood loop and 7 d in vivo rabbit model. Surface characterization assessments via atomic force microscopy show the durability of the submicron pattern after incorporation of NO donor S-nitroso-N-acetylpenicillamine (SNAP). The SNAP-doped catheters exhibited prolonged and controlled NO release mimicking the levels released by endothelium. Fabricated catheters showed cytocompatibility when evaluated against BJ human fibroblast cell lines. After 20h in vitro evaluation of catheters in a blood loop, textured-NO catheters exhibited a 13-times reduction in surface thrombus formation compared to the control catheters, which had 83% of the total area covered by clots. After the 7 d in vivo rabbit model, analysis on the catheter surface was examined via scanning electron microscopy, where significant reduction of platelet adhesion, fibrin mesh, and thrombi can be observed on the NO-releasing textured surfaces. Moreover, compared to relative controls, a 63% reduction in the degree of thrombus formation within the jugular vein was observed. Decreased levels of fibrotic tissue decomposition on the jugular vein and reduced platelet adhesion and thrombus formation on the texture of the NO-releasing catheter surface are indications of mitigated foreign body response. This study demonstrated a biocompatible and robust dual-functioning textured NO PU catheter in limiting fouling-induced complications for longer-term blood-contacting device applications. Statement of significanceCatheter-induced thrombosis is a major contributor to infectious and mechanical complications of biomaterials that lead to device failure. This study demonstrated a robust, biocompatible, dual-functioning textured nitric oxide (NO) polyurethane catheter in limiting fouling-induced complications for longer-term blood-contacting device applications.The fabricated catheters exhibited prolonged and controlled NO release that mimics endothelium levels. After the 7 d in vivo model, a significant reduction in platelet adhesion, fibrin mesh, and thrombi was observed on the NO-releasing textured catheters, along with decreased levels of fibrotic tissue decomposition on the jugular vein. Results illustrate that NO-textured catheter surface mitigates foreign body response.