Blood-contacting Devices Research Articles

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.

Tellurium-containing polymer coating with glutathione peroxidase mimics capability for surface modification of intravascular implants

Interventional therapy as an effective method has saved millions of lives of human, in which the interventional devices (e.g. central venous catheters, vascular stent, etc.) play a crucial role. However, undesirable implantation responses including thrombus formation, inflammation, and hyperplasia is still the life-threatening to the patients. In this study, a novel tellurium-functionalized polycarbonate-polyurethane (PCU-TeTe) was designed and synthesized by introducing ditelluride bonds (Te-Te) into the molecular structure of polymer. The developed PCU-TeTe showed an excellent catalytic activity in the nitric oxide (NO) release with a rate of 2.8 × 10-10 mol·cm−2·min−1, hence has multiple advanced functions in the blood environment. Both in vitro and ex vivo results of hemocompatibility showed that PCU-TeTe could substantially reduce the probability of thrombogenesis. Besides, PCU-TeTe could significantly promote endothelial cell (EC) proliferation while suppress the growth of smooth muscle cell (SMC) and macrophage (MA). Moreover, the in vivo results including qualitative and quantitative date (e.g. abdominal aorta hyperplasia) demonstrated that PCU-TeTe could not only promote healthy endothelialization, but also inhibit thrombus, inflammation and hyperplasia. Such tellurium-functionalized system could be a promising strategy for the design and fabrication of vascular materials or implants, especially for blood-contacting devices in the future.

A strategy of functional crosslinking acellular matrix in blood-contacting implantable devices with recombinant humanized collagen type III (rhCOLIII)

A large number of blood contacting implantable devices are used worldwide annually. Acellular matrix (AM), as one of the blood-contacting materials, has achieved a great success, since it remains the structures, components and certain functions of extracellular matrix. However, AM often fails during the period of service owing to non-ideal anticoagulation , severe inflammatory responses and poor mechanical properties. Herein, we specially prepared a newly designed tailored recombinant humanized collagen type III (rhCOLIII) that effectively removed the binding site to platelets while retaining cytocompatibility. In this study, a radical-polymerization-crosslinked decellularized porcine pericardium (DPP) with rhCOLIII and glycidyl methacrylate (GMA) through one-pot method was designed as artificial heart valves. Due to the introduction of rhCOLIII, the anticoagulation properties were dramatically improved with fewer platelets adhesion and less thrombogenesis. The mechanical properties of the novel heart valve (rhCOLIII/GMA-DPP) were significantly enhanced through radical polymerization crosslinking. Furthermore, experiments in vivo and vitro showed the inflammatory responses were moderately reduced. In conclusion, this study provides a simple strategy for functional crosslinking AM in blood-contacting implantable devices and shows possibilities for real application. • rhCOLIII possess both affinity for endothelial cells and anticoagulation property. • A simply radical polymerization crosslinking method for acellular matrix. • Functional crosslinked acellular matrix with rhCOLIII performs well as heart valves.

Recent Developments in Blood-Compatible Superhydrophobic Surfaces.

Superhydrophobic surfaces, as indicated in the name, are highly hydrophobic and readily repel water. With contact angles greater than 150° and sliding angles less than 10°, water droplets flow easily and hardly wet these surfaces. Superhydrophobic materials and coatings have been drawing increasing attention in medical fields, especially on account of their promising applications in blood-contacting devices. Superhydrophobicity controls the interactions of cells with the surfaces and facilitates the flowing of blood or plasma without damaging blood cells. The antibiofouling effect of superhydrophobic surfaces resists adhesion of organic substances, including blood components and microorganisms. These attributes are critical to medical applications such as filter membranes, prosthetic heart valves, extracorporeal circuit tubing, and indwelling catheters. Researchers have developed various methods to fabricate blood-compatible or biocompatible superhydrophobic surfaces using different materials. In addition to being hydrophobic, these surfaces can also be antihemolytic, antithrombotic, antibacterial, and antibiofouling, making them ideal for clinical applications. In this review, the authors summarize recent developments of blood-compatible superhydrophobic surfaces, with a focus on methods and materials. The expectation of this review is that it will support the biomedical research field by providing current trends as well as future directions.

Using Graphene-Based Materials for Stiff and Strong Poly(ethylene glycol) Hydrogels.

Blood-contacting devices are increasingly important for the management of cardiovascular diseases. Poly(ethylene glycol) (PEG) hydrogels represent one of the most explored hydrogels to date. However, they are mechanically weak, which prevents their use in load-bearing biomedical applications (e.g., vascular grafts, cardiac valves). Graphene and its derivatives, which have outstanding mechanical properties, a very high specific surface area, and good compatibility with many polymer matrices, are promising candidates to solve this challenge. In this work, we propose the use of graphene-based materials as nanofillers for mechanical reinforcement of PEG hydrogels, and we obtain composites that are stiffer and stronger than, and as anti-adhesive as, neat PEG hydrogels. Results show that single-layer and few-layer graphene oxide can strengthen PEG hydrogels, increasing their stiffness up to 6-fold and their strength 14-fold upon incorporation of 4% w/v (40 mg/mL) graphene oxide. The composites are cytocompatible and remain anti-adhesive towards endothelial cells, human platelets and Staphylococcus aureus, similar to neat hydrogels. To the best of our knowledge, this is the first work to report such an increase of the tensile properties of PEG hydrogels using graphene-based materials as fillers. This work paves the way for the exploitation of PEG hydrogels as a backbone material for load-bearing applications.

Strategies for Improving Endothelial Cell Adhesion to Blood-Contacting Medical Devices.

The endothelium is a critical mediator of homeostasis on blood-contacting surfaces in the body, serving as a selective barrier to regulate processes such as clotting, immune cell adhesion, and cellular response to fluid shear stress. Implantable cardiovascular devices, including stents, vascular grafts, heart valves, and left ventricular assist devices, are in direct contact with circulating blood and carry a high risk for platelet activation and thrombosis without a stable endothelial cell (EC) monolayer. Development of a healthy endothelium on the blood-contacting surface of these devices would help ameliorate risks associated with thrombus formation and eliminate the need for long-term antiplatelet or anticoagulation therapy. Although ECs have been seeded onto or recruited to these blood-contacting surfaces, most ECs are lost upon exposure to shear stress due to circulating blood. Many investigators have attempted to generate a stable EC monolayer by improving EC adhesion using surface modifications, material coatings, nanofiber topology, and modifications to the cells. Despite some success with enhanced EC retention in vitro and in animal models, no studies to date have proven efficacious for routinely creating a stable endothelium in the clinical setting. This review summarizes past and present techniques directed at improving the adhesion of ECs to blood-contacting devices. Impact statement Clinical success of blood-contacting devices such as vascular grafts, stents, and heart valves has remained limited by postimplantation problems, including thrombosis and loss of patency. Without a stable endothelial cell (EC) monolayer, blood-contacting devices are at risk for platelet activation and thrombosis. Methods to improve EC adhesion on these devices have not translated to long-term in vivo success, as many ECs are lost after exposure to circulating blood. In this study, we summarize methods to improve EC adhesion and retention. Successful endothelialization of blood-contacting devices may improve patient outcomes after device implantation and limit the need for long-term antiplatelet or anticoagulation therapy.

Preparation of superhydrophobic titanium surface via the combined modification of hierarchical micro/nanopatterning and fluorination

Adhesion of bacteria and platelets on blood-contact implants and surgical devices is one of the causes of infections and thrombus. A superhydrophobic surface serving as a protective layer can minimize adhesion and contamination due to the low surface energy. The objective of this paper is to construct a superhydrophobic surface on a titanium implant by a combination of a topological structure and chemical coating. First, a micro/nano hierarchical morphology is obtained by sandblasting, acid-etching, and anodic oxidation. Then, a low surface energy coating material (fluoroalkylsilane, as the example case in this study) is used to modify the surface further. The effects of the morphology of micro and/or nanoscales and corresponding fluorination on the wettability are investigated. The results show that a hierarchical surface with microroughness and nanotubes is successfully constructed, and the contact angle (CA) is 44.9°, indicating good hydrophilicity. Interestingly, after being modified by fluoroalkylsilane, the surface converted from hydrophilic to superhydrophobic with a CA of 151.4°. In contrast, the fluorination modification of single micro or nanofeatures cannot achieve superhydrophobicity, indicating that the micro/nanostructures may show a synergistic effect for an efficient fluorination coating later on. Overall, our results demonstrate the feasibility of achieving a superhydrophobic surface via the micro/nano topological patterning and fluorination modification. The proposed method is expected to enrich the preparation technologies of superhydrophobic titanium surfaces.Graphic abstract

Continuum modeling of thrombus formation and growth under different shear rates

Obstruction of blood flow due to thrombosis is a major cause of ischemic stroke, myocardial infarction, and in severe cases, mortality. In particular, in blood wetting medical devices, thrombosis is a common reason for failure. The prediction of thrombosis by understanding signaling pathways using computational models, lead to identify the risk of thrombus formation in blood-contacting devices and design improvements. In this study, a mathematical model of thrombus formation and growth is presented. A biochemical model of platelet activation and aggregation is developed to predict thrombus size and shape at the site of vascular injury. Computational fluid dynamics using the finite volume method is employed to compute the velocity and pressure fields which are influenced by the growing thrombi. The passive transport of platelets, agonists, the platelet activation kinetics, their adhesion to the growing thrombi and embolization of platelets are solved by a fully coupled set of convection–diffusion–reaction equations. The thrombogenic surface representing blood-contacting material or injured blood vessel was incorporated into the model as a surface flux boundary condition to initiate thrombus formation. The blood is considered as a Newtonian fluid, while the thrombus is treated as a porous medium. The results are compared with in vitro experiments of a microfluidic chamber at an initial inlet venous shear rate of 200s−1 using a pressure–inlet boundary condition. The thrombus development due to agonist concentrations and change in the shear rate as well as thromboembolism for this benchmark problem is successfully computed. Furthermore, to extend the current model to a physiologically relevant configuration, thrombus formation in a blood tube is simulated. Two different heterogeneous reaction rates for platelet aggregation are used to simulate thrombus growth under a constant inlet flow rate. The findings show that the thrombus shape can be substantially altered by the hemodynamic conditions, increase in the shear rate and due to the combined effects of shear induced platelet activation and the heterogeneous reaction rates. It is also concluded that the model is able to predict thrombus formation in different physiological and pathological hemodynamics.

Selenium-functionalized polycarbonate-polyurethane for sustained in situ generation of therapeutic gas for blood-contacting materials

Polyurethanes (PU) have been widely used in blood-contacting devices including indwelling implants and extracorporeal devices due to its good biocompatibility. However, the conventional PU also faces problems like thrombus formation and cell compatibility that could cause the treatment failure. In this study, a novel selenium-functionalized polycarbonate-polyurethane (PCU–SeSe) is developed based on the dynamic diselenide bond. Having diselenide bond-containing glycol as functional component, PCU-SeSe is endowed with glutathione peroxidase (GPx)-like catalytic activity, which could catalyze the release of nitric oxide (NO) continuously and controllably in the donor environment. This feature provides the materials with multiple functions from markedly suppressing platelet adhesion and activation, reducing the thrombogenesis, and enhancing the hemocompatibility. Meanwhile, PCU-SeSe could promote the growth of endothelial cell (EC) as well as significantly inhibit the growth of smooth muscle cell (SMC) and macrophage (MA) in vitro. The animal experiments including aortic implantation of sprague-dawley (SD) rats and stent implantation also demonstrate the abilities of endothelialization, thromboresistance, anti-inflammation, and anti-hyperplasia of PCU-SeSe in vivo. Overall, this study provides a new strategy for the designing of blood-contacting devices, which could be promising in the fabrication of cardiovascular biomaterials.

Cationic Fluoropolyphosphazenes: Synthesis and Assembly with Heparin as a Pathway to Hemocompatible Nanocoatings

The development of state-of-the-art blood-contacting devices can be advanced through integrating hemocompatibility, durability, and anticoagulant functionalities within engineered nanoscale coatings. To enable all-aqueous assembly of nanocoatings combining omniphobic fluorinated features with the potent anticoagulant activity of hydrophilic heparin, two fluoropolymers containing cationic functionalities were synthesized─poly[(trifluoroethoxy)(dimethylaminopropyloxy)phosphazene], PFAP-O, and poly[(trifluoroethoxy)(dimethylaminopropylamino)phosphazene], PFAP-A. Despite a relatively high content of fluorinated pendant groups─approximately 50% (mol) in each─both polymers displayed solubility in aqueous solutions and were able to spontaneously form stable supramolecular complexes with heparin, as determined by dynamic light scattering and asymmetric flow field-flow fractionation methods. Heparin-containing coatings were then assembled by layer-by-layer deposition in aqueous solutions. Nanoassembled coatings were evaluated for potential thrombogenicity in three important categories of in vitro tests─coagulation by thrombin generation, platelet retention, and hemolysis. In all assays, heparin-containing fluoro-coatings consistently displayed superior performance compared to untreated titanium surfaces or fluoro-coatings assembled using poly(acrylic acid) in the absence of heparin. Short-term stability studies revealed the noneluting nature of these noncovalently assembled coatings.

Blood-incompatibility in haemodialysis: alleviating inflammation and effects of coagulation.

ABSTRACTBlood-incompatibility is an inevitability of all blood-contacting device applications and therapies, including haemodialysis (HD). Blood leaving the environment of blood vessels and the protection of the endothelium is confronted with several stimuli of the extracorporeal circuit (ECC), triggering the activation of blood cells and various biochemical pathways of plasma. Prevention of blood coagulation, a major obstacle that needed to be overcome to make HD possible, remains an issue to contend with. While anticoagulation (mainly with heparin) successfully prevents clotting within the ECC to allow removal of uraemic toxins across the dialysis membrane wall, it is far from ideal, triggering heparin-induced thrombocytopenia in some instances. Soluble fibrin can form even in the presence of heparin and depending on the constitution of the patient and activation of platelets, could result in physical clots within the ECC (e.g. bubble trap chamber) and, together with other plasma and coagulation proteins, result in increased adsorption of proteins on the membrane surface. The buildup of this secondary membrane layer impairs the transport properties of the membrane to reduce the clearance of uraemic toxins. Activation of complement system-dependent immune response pathways leads to leukopenia, formation of platelet–neutrophil complexes and expression of tissue factor contributing to thrombotic processes and a procoagulant state, respectively. Complement activation also promotes recruitment and activation of leukocytes resulting in oxidative burst and release of pro-inflammatory cytokines and chemokines, thereby worsening the elevated underlying inflammation and oxidative stress condition of chronic kidney disease patients. Restricting all forms of blood-incompatibility, including potential contamination of dialysis fluid with endotoxins leading to inflammation, during HD therapies is thus still a major target towards more blood-compatible and safer dialysis to improve patient outcomes. We describe the mechanisms of various activation pathways during the interaction between blood and components of the ECC and describe approaches to mitigate the effects of these adverse interactions. The opportunities to develop improved dialysis membranes as well as implementation strategies with less potential for undesired biological reactions are discussed.

The porcine abattoir blood model-Evaluation of platelet function for in-vitro hemocompatibility investigations.

The major obstacle of blood-contacting medical devices is insufficient hemocompatibility, particularly thrombogenicity and platelet activation. Pre-clinical in-vitro testing allows for the evaluation of adverse thrombogenicity-related events, but is limited, among others, by the availability and quantity of human blood donations. The use of animal blood is an accepted alternative for several tests; however, animal and particularly abattoir blood might present species-specific differences to human blood as well as elevated blood values, and pre-activated platelets due to stressed animals and non-standardized blood collection. To this end, we investigated porcine abattoir blood in comparison to human donor blood with the focus on platelet pre-activation and remaining activation potential. By means of light transmission aggregometry, aggregation kinetics of platelet rich plasma after stimulation with three different concentrations of each adenosine diphosphate (ADP) (5µM, 10µM, 20µM) and collagen (2.5µg/ml, 5µg/ml, 10µg/ml) were monitored. The activation with collagen revealed no significant differences in platelet behavior of the two species. In contrast, stimulation with ADP resulted in a lower maximum aggregation and a high disaggregation for porcine abattoir blood. The latter is a species-specific phenomenon of porcine platelets. Variations within each study cohort were comparable for human and abattoir pig. The similarities in platelet activation following collagen stimulation and the preservation of the porcine-specific reaction to ADP prove a general functionality of the abattoir blood. This finding provides a first step towards the complete validation of the porcine abattoir blood model.

Discrete responses of erythrocytes, platelets, and von Willebrand factor to shear

Despite decades of technological advancements in blood-contacting medical devices, complications related to shear flow-induced blood trauma are still frequently observed in clinic. Blood trauma includes haemolysis, platelet activation, and degradation of High Molecular Weight von Willebrand Factor (HMW vWF) multimers, all of which are dependent on the exposure time and magnitude of shear stress. Specifically, accumulating evidence supports that when blood is exposed to shear stresses above a certain threshold, blood trauma ensues; however, it remains unclear how various constituents of blood are affected by discrete shears experimentally. The aim of this study was to expose blood to discrete shear stresses and evaluate blood trauma indices that reflect red cell, platelet, and vWF structure. Citrated human whole blood (n = 6) was collected and its haematocrit was adjusted to 30 ± 2% by adding either phosphate buffered saline (PBS) or polyvinylpyrrolidone (PVP). Viscosity of whole blood was adjusted to 3.0, 12.5, 22.5 and 37.5 mPa·s to yield stresses of 3, 6, 9, 12, 50, 90 and 150 Pa in a custom-developed shearing system. Blood samples were exposed to shear for 0, 300, 600 and 900 s. Haemolysis was measured using spectrophotometry, platelet activation using flow cytometry, and HMW vWF multimer degradation was quantified with gel electrophoresis and immunoblotting. For tolerance to 300, 600 and 900 s of exposure time, the critical threshold of haemolysis was reached after blood was exposed to 90 Pa for 600 s (P < 0.05), platelet activation and HMW vWF multimer degradation were 50 Pa for 600 s and 12 Pa for 300 s respectively (P < 0.05). Our experimental results provide simultaneous comparison of blood trauma indices and thus also the relation between shear duration and magnitude required to induce damage to red cells, platelets, and vWF. Our results also demonstrate that near-physiological shear stress (<12 Pa) is needed in order to completely avoid any form of blood trauma. Therefore, there is an urgent need to design low shear-flow medical devices in order to avoid blood trauma in this blood-contacting medical device field.

Thrombogenicity of biomaterials depends on hemodynamic shear rate.

While it is well recognized that different biomaterials induce thrombosis at low shear rates, the effect of high shear rates may be quite different. We hypothesize that the amount of thrombus formation on a given material can be greatly influenced by the local shear rate. We tested this hypothesis with two different whole blood perfusion loop assays to quantify biomaterial thrombogenicity as a function of shear stress. One assay uses obstructive posts (pins) of material positioned centrally in a tube perfused at high shear rate of >5000/s for 24h. A second assay uses a parallel plate chamber to perfuse low (<150/s), medium (~500/s), and high shear rates over 96h. We evaluated the thrombogenicity of seven different biomaterials including stainless steel, acrylic, ceramic, Dacron, polytetrafluoroethylene (PTFE), silicone, and polyvinyl chloride (PVC). For the pin assay, thrombus mass was significantly greater for stainless steel than either zirconia ceramic or acrylic (p<0.001). Similarly, the parallel plate chamber at high shear showed that steel and PTFE (p<0.02) occluded the chamber faster than acrylic. In contrast, a low shear parallel plate chamber revealed that stainless steel and PTFE were least thrombogenic, while silicone, Dacron, and other plastics such as acrylic were most thrombogenic. Histology revealed that high shear thrombi had a large proportion of platelets not seen in the low shear fibrin-rich thrombi. This differential thrombogenicity based on shear rate conditions may be important in the selection of biomaterials for blood-contacting devices.

On the origin of better hemocompatibility of the BCxNyOz coatings

The development of hemocompatible coatings on metallic implants is one of the challenges for blood-contacting implantable devices. In this paper, we investigated the blood-material interaction of BCxNyOz coatings deposited on Ti-6Al-4V substrates, using reactive radiofrequency magnetron sputtering technique with variation in nitrogen (N2) flow rate. A series of experiments, including hemolysis tests, erythrocytes, and platelets adhesion and activation analysis, dynamic blood coagulation, and plasma recalcification time tests, were performed to understand the blood-material interactions, qualitatively and quantitatively. The results revealed that the degree of hemolysis on all the samples was below 2.5%, suggesting their favourable interaction with RBCs. The interactions between erythrocytes and platelets with all the BCxNyOz coatings were reduced significantly compared to Ti-6Al-4V. BCxNyOz coatings could substantially delay the time of blood coagulation to the period of 60 min. The plasma recalcification time of coatings was also increased significantly. An effort has been made to rationalize the difference in hardness or blood compatibility parameters in terms of [N]/[B] or [N]/[C] ratio. The present study conclusively establishes that BCxNyOz coatings can significantly enhance hemocompatibility, thereby opening up a myriad of biomedical applications.

Oriented homo-epitaxial crystallization of polylactic acid displaying a biomimetic structure and improved blood compatibility.

Epitaxial crystallization and solid hot-drawing technology were employed to fabricate oriented homo-epitaxial crystallization of polylactic acid (PLA) with nano-topography to enhance its blood compatibility and mechanical characteristics as blood-contacting medical devices. The process involved solid hot stretching the PLA plates. A PLA nutrient solution was then used to immerse the oriented plates to dissolve some of the PLA solutes, ensuring plate integrity. Consequently, the drawing process exponentially enhanced the modulus and tensile strength of the PLA. Orientation and epitaxial crystallization could substantially enhance blood compatibility of PLA by prolonging clotting time and decreasing hemolysis rate, protein adsorption, and platelet activation. The oriented homo-epitaxial crystallization of PLA exhibited a nano-topography and fibrous structure similar to the intimal layer of a blood vessel, and this biomimetic structure was advantageous in decreasing the activation and/or adhesion of platelets.

Differences in human and minipig platelet number, volume and activation induced by borosilicate glass beads in a modified chandler loop-system.

The pig 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 Russel and Burchs' 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 mostly for compatibility with human blood. The aim of this study was therefore to determine whether there are differences in behavior of porcine and human platelets when they come into contact with glass, which was used as an exemplary thrombogenic material. For this purpose changes of 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 blood flow. Minipig and human platelets showed significant differences in number and volume, but not in activation after 4-8 min exposure to glass.

In vitro biocompatibility testing of polymeric nanofiber scaffolds: fine-tuning for a better prediction of the in vivo behaviour

Abstract Biomaterial research efforts focus on the development of biomaterials that mimic the natural extracellular environment. In addition, different strategies are applied to render materials for blood-contacting devices nonthrombogenic through surface modifications that would suppress activation of platelets, coagulation and the complement system. A confluent thin layer of endothelial cells lines all blood vessels and produces factors responsible for inhibition of coagulation, thrombosis and neointimal hyperplasia. Thus, the ability to rapidly form a healthy endothelium upon implantation represents a desired property of biomaterials used for cardiovascular devices. In this study we used advanced in vitro methods to investigate the biocompatibility of a biodegradable and a permanent electrospun nanofiber fabric, poly-L-lactic acid and polycarbonate-based silicone elastomer respectively, with the focus on endothelialization and hemocompatibility.

A modular in vitro flow model to analyse blood-surface interactions under physiological conditions

Abstract Newly developed materials for blood-contacting devices need to undergo hemocompatibility testing to prove compliance with clinical requirements. However, many current in vitro models disregard the influence of flow conditions and blood exchange as it occurs in vivo. Here, we present a flow model which allows testing of blood-surface interactions under more physiological conditions. This modular platform consists of a triple-pump-chip and a microchannel-chip with a customizable surface. Flow conditions can be adjusted individually within the physiological range. A performance test with whole blood confirmed the hemocompatibility of our modular platform. Hemolysis was negligible, inflammation and hemostasis parameters were comparable to those detected in a previously established quasi-static whole blood screening chamber. The steady supply of fresh blood avoids secondary effects by nonphysiological accumulation of activation products. Experiments with three subsequently tested biomaterials showed results similar to literature and our own experience. The reported results suggest that our developed flow model allows the evaluation of blood-contacting materials under physiological flow conditions. By adjusting the occurring wall shear stress, the model can be adapted for selected test conditions.

Laser Assisted Size Reduction of Gold (Au) Particles onto a Titanium (Ti) Substrate Surface

This paper aims to perform laser assisted size reduction to nanoparticles of gold (Au) sputtered layer on titanium (Ti) base material using an innovative method that could potentially be applied in novel blood contact and thromboresistive devices in the living body, such as ventricular assist devices (VADs). The enrichment of the surface layer of titanium with gold nanoparticles, due to its bioproperties, may contribute to the reduction of inflammatory reactions and infections occurring mainly in the first postoperative period causing implant failure. The possibility of obtaining superficial size reduction and/or bonding of nano gold particles with Ti micromachining by picosecond laser treatment was evaluated. The quantitative assessment of the particles has been made using SEM and are depicted on the histograms, whereby the appropriate number of particles determine the antibacterial properties and health safety. The initial analysis of micromachining process of the prepared material was focused on power-depth dependence by confocal microscopy. The evaluation of gold particles was conducted using scanning electron microscopy (SEM) using SE and QBSD detectors with energy dispersive spectroscopy (EDS) analysis. Attempts to reduce the deposited gold coating to the size of Au nanoparticles and to melt them into titanium matrix using a laser beam have been successfully completed. There seems to be no strict relationship between particle size distribution of gold onto Ti, probably due to too low energy to excite titanium enough, resulting from difference in Ti and Au melting point temperatures. However, the obtained results allow continuation of pilot studies for augmented research and material properties analysis in the future.