Blood purification therapy is widely used in patients with renal insufficiency and severe infections, where membrane-associated thrombosis is a side effect. How to improve the hemocompatibility of ...dialysis membranes and reduce thrombosis is a focus of current research, in which platelets play a key role. However, few dialysis membranes that directly inhibit platelets have been developed to date. In this study, a polyethersulfone (PES) membrane was modified with ticagrelor, a platelet P2Y12 receptor inhibitor, and detailed characterization was performed. The ticagrelor modified PES membrane (TMPES) showed good hydrophilicity and anti-protein adsorption and significantly inhibited platelet adhesion, aggregation, and activation, which demonstrated good antithrombotic properties. In addition, the membrane had excellent red blood cell (RBC) compatibility, anticoagulant, and antiinflammatory effects, which demonstrated superior biosafety in cell and animal experiments. Therefore, the TMPES dialysis membrane could have potential in clinical applications.
•Blood purification therapy is widely used in renal insufficiency patients, and membrane associated thrombosis is a side effect.•The inhibition of platelet P2Y12 receptor as a targeted treatment can reduce thrombosis of dialysis membrane.
Display omitted
•The method of synthesis and post-processing of fluorescent probe (BICL) is simple.•BICL becomes the first fluorescent probe to detect citric acid.•BICL can be used to detect the H+ ...change by colorimetric and ratiometric methods.•BICL has good blood compatibility and fluorescence imaging effect.•BICL can be used in zebra fish to detect acid pH and citric acid with good time stability.
Rapid, accurate and efficient detection of acidic pH and citric acid (CA) changes is of great significance for predicting environmental and food safety problems by fluorescence analysis technique. Herein, a small molecule ratiometric fluorescent probe (BICL) based on benzoindole derivatives is successfully synthesized and characterized and used for quantitatively and qualitatively “turn-on” detection acid pH and CA changes in solution and environment by ultraviolet spectrum and fluorescence emission spectrum. On the one hand, the probe has a good linear relation to acidic pH in the pH range 3.1–4.5 (I604/I550 = 13.088–2.3878pH, R2 = 0.9986). On the other hand, the probe has a good linear relationship in the range of CA concentration of 14.0–23.0 μM (I604/I550 = 0.5324 CA-5.2628, R2 = 0.9993) and a low detection limit of 2.967 μM. BICL has a good recovery rate in the range of 114.6 ~ 101.0% and a low relative standard deviation (RSD) (0.0011 ~ 0.0092) in the determination of CA in real samples (water, drinks and fruits), which holds great potential for application in determination of CA in real samples. Importantly, the probe has good blood compatibility, and it has been successfully applied to detect exogenously induced changes in acidic pH and CA in zebrafish with great time-stability by using fluorescence imaging technology, respectively.
•Asymmetric PEGylated PES membrane, with a thin dense layer atop and a microporous support layer beneath, successfully synthesized via simple thermal cross-linking and NIPs.•Excellent ...hemocompatibility displayed by PEGylated PES membrane in terms of protein adsorption, hemolysis, platelet adhesion and blood clotting.•Long-lasting surface stability, structure stability against wetting as well as cytocompatibility exhibited by PEGylated PES membrane.
Excellent hemocompatibility and long-term stability against blood wetting are important properties required for artificial lung membrane, the core component in extracorporeal membrane oxygenator which is life-saving for patients with severe lung dysfunctions. Herein, novel hydrophilic modified polyethersulfone (PES) asymmetric membranes were synthesized via thermal cross-linking, and characterization via SEM, FTIR, 1H NMR and surface water contact angle measurements demonstrated that the modified asymmetric membranes composing a dense layer with hydrophilic surface on top of a microporous support layer were successfully fabricated without any observed defects. Among all the modified membranes, PEGylated PES membrane exhibited the smoothest membrane surface, improved mechanical property, good gas permeability and the best performance in hemocompatibility in terms of blood coagulation, protein adsorption and platelet adhesion. Moreover, the PEGylated PES membrane showed excellent long-term stability in membrane surface wettability as well as long-term stable performance against blood fouling and wetting. This research work provides valuable insights and new idea into synthesizing membranes, with simple synthesis process, long lasting high hemocompatibility and stability against wetting, for application as artificial lung membranes.
•A thin dense layer of PTFPMS successfully coated on PEI microporous substrate with no observed defects, showing thermal stability, hydrophobicity and electronegativity.•Improved CO2/O2 gas ...permeation exhibited by PTFPMS/PEI composite membrane with good CO2/O2 selectivity at atmospheric pressure and room temperature.•Impressive hemocompatibility displayed by PTFPMS/PEI composite membrane in terms of hemolysis, protein adsorption, platelet adhesion and blood recalcification time.•Excellent long-term anti-fouling performance exhibited by PTFPMS/PEI composite membrane.
The tradeoff between efficient gas exchange and blood leakage as well as thrombosis caused by contact between blood and membrane are existing challenges in extracorporeal membrane oxygenation (ECMO). Herein, poly (3,3,3-trifluoropropyl) methylsiloxane/polyetherimide (PTFPMS/PEI) composite membranes, with a thin PTFPMS dense layer for functional CO2 and O2 exchange coated on microporous PEI substrate membrane for mechanical support, were synthesized, characterized and evaluated for potential application as oxygenation membrane. Characterization data from scanning electron microscopy with energy dispersive spectroscopy, thermogravimetric analysis, contact angle and zeta potential measurements confirmed that PTFPMS/PEI composite membrane with different coating concentrations were successfully prepared, and the composite membranes obtained exhibited thermal stability, surface hydrophobicity as well as surface electronegativity. Analysis on gas permeance and hemocompatibility performance demonstrated that the composite membranes displayed effective gas transfer and good blood compatibility in terms of hemolysis rate, protein adsorption, platelet adhesion as well as plasma recalcification time. More notably, the membrane also displayed excellent long term anti-fouling performance. In summary, the PTFPMS/PEI composite membrane showed impressive application potential for use as oxygenation membrane in ECMO.
Blood contact with biomaterials triggers activation of multiple reactive mechanisms that can impair the performance of implantable medical devices and potentially cause serious adverse clinical ...events. This includes thrombosis and thromboembolic complications due to activation of platelets and the coagulation cascade, activation of the complement system, and inflammation. Numerous surface coatings have been developed to improve blood compatibility of biomaterials. For more than thirty years, the anticoagulant drug heparin has been employed as a covalently immobilized surface coating on a variety of medical devices. This review describes the fundamental principles of non-eluting heparin coatings, mechanisms of action, and clinical applications with focus on those technologies which have been commercialized. Because of its extensive publication history, there is emphasis on the CARMEDA® BioActive Surface (CBAS® Heparin Surface), a widely used commercialized technology for the covalent bonding of heparin.
Display omitted
It is of great significance to develop micro/nanomotors with good biosafety and high efficiency for biomedical detection. In order to enhance the contact chances between the biosensors and the ...analytes in the complex blood sample, we report a near-infrared light (NIR)-driven fluorescent nanomotor, which can safely and efficiently capture and detect circulating tumor cells (CTCs) in the whole blood environment without pretreating procedures. Firstly, the structure of the fluorescent nanomotor was characterized and its motion behavior in different environments was analyzed. Subsequently, CTCs detection conditions were optimized to explore the effect of nanoscale autonomous mixing provided by nanomotor’s motion behavior on the efficiency of CTCs capture. The results showed that the NIR-driven fluorescent nanomotor can keep moving in the complex biological medium so as to increase their contact chances with CTCs and improve the binding efficiency with the target analyte (the capture efficiency increased from 67.5% – 85% (no NIR irradiation) to 93.75–98.75% (under NIR irradiation)). Finally, due to the excellent fluorescence properties of the nanomotors, they can be applied to the visual detection of the whole blood samples obtained from clinical cancer patients. The NIR-driven nanomotor designed in this paper can detect CTCs in whole blood environment, which is a beneficial extension of the existing cell detection system of most micro/nanomotors in water phase environment.
Display omitted
•A novel near-infrared driven nanomotor for detecting circulating tumor cells (CTCs) was proposed in this work.•The capture efficiency of CTCs by nanomotors was improved significantly owing to their motion ability.•Nanomotors with good biocompatibility were used to capture and detect CTCs in clinical blood samples.
Display omitted
The adsorption of proteins is the initiating event in the processes occurring when blood contacts a “foreign” surface in a medical device, leading inevitably to thrombus formation. ...Knowledge of protein adsorption in this context has accumulated over many years but remains fragmentary and incomplete. Moreover, the significance and relevance of the information for blood compatibility are not entirely agreed upon in the biomaterials research community. In this review, protein adsorption from blood is discussed under the headings “agreed upon” and “not agreed upon or not known” with respect to: protein layer composition, effects on coagulation and complement activation, effects on platelet adhesion and activation, protein conformational change and denaturation, prevention of nonspecific protein adsorption, and controlling/tailoring the protein layer composition.
This paper is part 2 of a series of 4 reviews discussing the problem of biomaterial associated thrombogenicity. The objective was to highlight features of broad agreement and provide commentary on those aspects of the problem that were subject to dispute. We hope that future investigators will update these reviews as new scholarship resolves the uncertainties of today.
The artificial lung (AL) technology is one of the membrane-based artificial organs that partly augments lung functions, i.e. blood oxygenation and CO2 removal. It is generally employed as an ...extracorporeal membrane oxygenation (ECMO) device to treat acute and chronic lung-failure patients, and the recent outbreak of the COVID-19 pandemic has re-emphasized the importance of this technology. The principal component in AL is the polymeric membrane oxygenator that facilitates the O2/CO2 exchange with the blood. Despite the considerable improvement in anti-thrombogenic biomaterials in other applications (e.g., stents), AL research has not advanced at the same rate. This is partly because AL research requires interdisciplinary knowledge in biomaterials and membrane technology. Some of the promising biomaterials with reasonable hemocompatibility — such as emerging fluoropolymers of extremely low surface energy - must first be fabricated into membranes to exhibit effective gas exchange performance. As AL membranes must also demonstrate high hemocompatibility in tandem, it is essential to test the membranes using in-vitro hemocompatibility experiments before in-vivo test. Hence, it is vital to have a reliable in-vitro experimental protocol that can be reasonably correlated with the in-vivo results. However, current in-vitro AL studies are unsystematic to allow a consistent comparison with in-vivo results. More specifically, current literature on AL biomaterial in-vitro hemocompatibility data are not quantitatively comparable due to the use of unstandardized and unreliable protocols. Such a wide gap has been the main bottleneck in the improvement of AL research, preventing promising biomaterials from reaching clinical trials. This review summarizes the current state-of-the-art and status of AL technology from membrane researcher perspectives. Particularly, most of the reported in-vitro experiments to assess AL membrane hemocompatibility are compiled and critically compared to suggest the most reliable method suitable for AL biomaterial research. Also, a brief review of current approaches to improve AL hemocompatibility is summarized.
The importance of Artificial Lung (AL) technology has been re-emphasized in the time of the COVID-19 pandemic. The utmost bottleneck in the current AL technology is the poor hemocompatibility of the polymer membrane used for O2/CO2 gas exchange, limiting its use in the long-term. Unfortunately, most of the in-vitro AL experiments are unsystematic, irreproducible, and unreliable. There are no standardized in-vitro hemocompatibility characterization protocols for quantitative comparison between AL biomaterials. In this review, we tackled this bottleneck by compiling the scattered in-vitro data and suggesting the most suitable experimental protocol to obtain reliable and comparable hemocompatibility results. To the best of our knowledge, this is the first review paper focusing on the hemocompatibility challenge of AL technology.
Display omitted
Restenosis, thrombosis formation and delayed endothelium regeneration continue to be problematic for coronary artery stent therapy. To improve the hemocompatibility of the cardiovascular implants and ...selectively direct vascular cell behavior, a novel kind of heparin/poly-l-lysine (Hep/PLL) nanoparticle was developed and immobilized on a dopamine-coated surface. The stability and structural characteristics of the nanoparticles changed with the Hep:PLL concentration ratio. A Hep density gradient was created on a surface by immobilizing nanoparticles with various Hep:PLL ratios on a dopamine-coated surface. Antithrombin III binding quantity was significantly enhanced, and in plasma the APTT and TT times as coagulation tests were prolonged, depending on the Hep density. A low Hep density is sufficient to prevent platelet adhesion and activation. The sensitivity of vascular cells to the Hep density is very different: high Hep density inhibits the growth of all vascular cells, while low Hep density could selectively inhibit smooth muscle cell hyperplasia but promote endothelial progenitor cells and endothelial cell proliferation. These observations provide important guidance for modification of surface heparinization. We suggest that this method will provide a potential means to construct a suitable platform on a stent surface for selective direction of vascular cell behavior with low side effects.
PDF
