GPVI-mediated thrombus stabilization of shear-induced platelet aggregates in a microfluidic stenosis.

Supraphysiological shear rates (>2000 s) amplify von Willebrand factor unfurling and increase platelet activation and adhesion. These elevated shear rates and shear rate gradients also play a role in shear-induced platelet aggregation (SIPA). The primary objective of this study is to investigate the contributions of major binding receptors to platelet deposition and SIPA in a stenotic model.

The effects of submicron-textured surface topography on antibiotic efficacy against biofilms.

Submicron-textured surfaces have been a promising approach to mitigate biofilm development and control microbial infection. However, the use of the single surface texturing approach is still far from ideal for achieving complete control of microbial infections on implanted biomedical devices. The use of a surface topographic modification that might improve the utility of standard antibiotic therapy could alleviate the complications of biofilms on devices.

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.

In Vitro and In Vivo Assessment of the Infection Resistance and Biocompatibility of Small-Molecule-Modified Polyurethane Biomaterials.

Bacterial intracellular nucleotide second messenger signaling is involved in biofilm formation and regulates biofilm development. Interference with the bacterial nucleotide second messenger signaling provides a novel approach to control biofilm formation and limit microbial infection in medical devices. In this study, we tethered small-molecule derivatives of 4-arylazo-3,5-diamino-1-pyrazole on polyurethane biomaterial surfaces and measured the biofilm resistance and initial biocompatibility of modified biomaterials in and settings.

FXII contact activation products have an inhibitory effect on αFXIIa.

It is accepted that the contact activation complex of the intrinsic pathway of blood coagulation cascade produces active enzymes that lead to plasma coagulation following biomaterial contact. In this study, FXII was activated through contact with hydrophilic glass beads and hydrophobic octadecyltrichlorosilane-modified glass beads from neat buffer solutions. These FXII contact activation products generated from material interaction were found to suppress the procoagulant activity of exogenous αFXIIa, and this inhibition was dependent on surface wettability and the concentration of exogenous αFXIIa.

In vitro evaluation of blood plasma coagulation responses to four medical-grade polyurethane polymers.

Segmented polyurethane (PU) block copolymers are widely used in implantable cardiovascular medical devices due to their good biocompatibility and excellent mechanical properties. More specifically, PU Biospan MS/0.4 was used in ventricular assist devices over the past decades.

Surfaces modified with small molecules that interfere with nucleotide signaling reduce Staphylococcus epidermidis biofilm and increase the efficacy of ciprofloxacin.

Staphylococcus epidermidis are common bacteria associated with biofilm related infections on implanted medical devices. Antibiotics are often used in combating such infections, but they may lose their efficacy in the presence of biofilms. Bacterial intracellular nucleotide second messenger signaling plays an important role in biofilm formation, and interference with the nucleotide signaling pathways provides a possible way to control biofilm formation and to increase biofilm susceptibility to antibiotic therapy.

Nucleotide Messenger Signaling of Staphylococci in Responding to Nitric Oxide - Releasing Biomaterials.

Nitric oxide (NO) releasing biomaterials are a promising approach against medical device associated microbial infection. In contrast to the bacteria-killing effects of NO at high concentrations, NO at low concentrations serves as an important signaling molecule to inhibit biofilm formation or disperse mature biofilms by regulating the intracellular nucleotide second messenger signaling network such as cyclic dimeric guanosine monophosphate (c-di-GMP) for many Gram-negative bacterial strains. However, Gram-positive staphylococcal bacteria are the most commonly diagnosed microbial infections on indwelling devices, but much less is known about the nucleotide messengers and their response to NO as well as the mechanism by which NO inhibits biofilm formation.

Crosslinkable fluorophenoxy-substituted poly[bis(octafluoropentoxy) phosphazene] biomaterials with improved antimicrobial effect and hemocompatibility.

Biomaterial-associated microbial infection is one of the most frequent and severe complications associated with the use of biomaterials in medical devices. In previous studies, we developed new fluorinated polyphosphazenes, poly[bis(octafluoropentoxy) phosphazene] (OFP) and crosslinkable OFP (X-OFP), and demonstrated the inhibition of bacterial adhesion and biofilm formation, thereby controlling microbial infection. In this study, two additional fluorinated polyphosphazenes (PPs, defined as LS02 and LS03) with fluorophenoxy-substituted side groups, 4-fluorophenoxy and 4-(trifluoromethyl)phenoxy, respectively, based on X-OFP general structure, were synthesized and applied as coatings on stainless steel.

Kinetic and Dynamic Effects on Degradation of von Willebrand Factor.

The loss of high molecular weight multimers (HMWM) of von Willebrand factor (vWF) in aortic stenosis (AS) and continuous-flow left ventricular assist devices (cf-LVADs) is believed to be associated with high turbulent blood shear. The objective of this study is to understand the degradation mechanism of HMWM in terms of exposure time (kinetic) and flow regime (dynamics) within clinically relevant pathophysiologic conditions. A custom high-shear rotary device capable of creating fully controlled exposure times and flows was used.

Submicron topography design for controlling staphylococcal bacterial adhesion and biofilm formation.

Surface topography modification with nano- or micro-textured structures has been an efficient approach to inhibit microbial adhesion and biofilm formation and thereby to prevent biomaterial-associated infection without modification of surface chemistry/bulk properties of materials and without causing antibiotic resistance. This manuscript focuses on submicron-textured patterns with ordered arrays of pillars on polyurethane (PU) biomaterial surfaces in an effort to understand the effects of surface pillar features and surface properties on adhesion and colonization responses of two staphylococcal strains. Five submicron patterns with a variety of pillar dimensions were designed and fabricated on PU film surfaces and bacterial adhesion and biofilm formation of Staphylococcal strains (Staphylococcus epidermidis RP62A and Staphylococcus aureus Newman D2C) were characterized.

Surface Texturing and Combinatorial Approaches to Improve Biocompatibility of Implanted Biomaterials.

Biomaterial associated microbial infection and blood thrombosis are two of the barriers that inhibit the successful use of implantable medical devices in modern healthcare. Modification of surface topography is a promising approach to combat microbial infection and thrombosis without altering bulk material properties necessary for device function and without contributing to bacterial antibiotic resistance. Similarly, the use of other antimicrobial techniques such as grafting poly(ethylene glycol) (PEG) and nitric oxide (NO) release also improve the biocompatibility of biomaterials.

Inhibition of bacterial adhesion and biofilm formation by a textured fluorinated alkoxyphosphazene surface.

The utilization of biomaterials in implanted blood-contacting medical devices often induces a persistent problem of microbial infection, which results from bacterial adhesion and biofilm formation on the surface of biomaterials. In this research, we developed new fluorinated alkoxyphosphazene materials, specifically poly[bis(octafluoropentoxy) phosphazene] (OFP) and crosslinkable OFP (X-OFP), with improved mechanical properties, and further modified the surface topography with ordered pillars to improve the antibacterial properties. Three X-OFP materials, X-OFP, X-OFP X-OFP, with different crosslinking densities were synthesized, and textured films with patterns of 500/500/600 nm (diameter/spacing/height) were fabricated via a two stage soft lithography molding process.

Influence of dielectric coatings on pin-to-rod nanosecond-pulsed discharges in phosphate-buffered saline.

Plasma medicine is a rapidly expanding field that utilizes non-equilibrium plasma discharges at atmospheric conditions or in liquids for clinical applications. There is significant interest in the production of plasma in the liquid phase for wastewater treatment, agricultural applications, and medical purposes. However, little investigation has been done about the effects of dielectric coatings on submerged electrodes, which is of significant interest to limit electrical current flow in the liquid.

New cross-linkable poly[bis(octafluoropentoxy) phosphazene] biomaterials: Synthesis, surface characterization, bacterial adhesion, and plasma coagulation responses.

Biomaterial-associated microbial infection and thrombosis represent major issues to the success of long-term use of implantable blood-contacting medical devices. The development of new poly[bis(octafluoropentoxy) phosphazene (OFP) biomaterials provides new routes for combatting microbial infection and thrombosis. However, the limited mechanical properties of OFP to date render them unsuitable for application in medical devices and inhibit any attempts at subsequent surface topography modification.

Antibacterial effects of low-temperature plasma generated by atmospheric-pressure plasma jet are mediated by reactive oxygen species.

Emergence and spread of antibiotic resistance calls for development of non-chemical treatment options for bacterial infections. Plasma medicine applies low-temperature plasma (LTP) physics to address biomedical problems such as wound healing and tumor suppression. LTP has also been used for surface disinfection.

The blood compatibility challenge. Part 3: Material associated activation of blood cascades and cells.

Following protein adsorption/activation which is the first step after the contact of material surfaces and whole blood (part 2), fibrinogen is converted to fibrin and platelets become activated and assembled in the form of a thrombus. This thrombus formation is the key feature that needs to be minimized in the creation of materials with low thrombogenicity. Further aspects of blood compatibility that are important on their own are complement and leukocyte activation which are also important drivers of thrombus formation.

Increased circulating microparticles in streptozotocin-induced diabetes propagate inflammation contributing to microvascular dysfunction.

Key Points: Circulating microparticles (MPs) are elevated in many cardiovascular diseases and have been considered as biomarkers of disease prognosis; however, current knowledge of MP functions has been mainly derived from in vitro studies and their precise impact on vascular inflammation and disease progression remains obscure. Using a diabetic rat model, we identified a >130-fold increase in MPs in plasma of diabetic rats compared to normal rats, the majority of which circulated as aggregates, expressing multiple cell markers and largely externalized phosphatidylserine; vascular images illustrate MP biogenesis and their manifestations in microvessels of diabetic rats. Using combined single microvessel perfusion and systemic cross-transfusion approaches, we delineated how diabetic MPs propagate inflammation in the vasculature and transform normal microvessels into an inflammatory phenotype observed in the microvessels of diabetic rats.

Blood coagulation response and bacterial adhesion to biomimetic polyurethane biomaterials prepared with surface texturing and nitric oxide release.

A dual functional polyurethane (PU) film that mimics aspects of blood vessel inner surfaces by combining surface texturing and nitric oxide (NO) release was fabricated through a soft lithography two-stage replication process. The fabrication of submicron textures on the polymer surface was followed by solvent impregnation with the NO donor, S-nitroso-N-acetylpenicillamine (SNAP). An in vitro plasma coagulation assay showed that the biomimetic surface significantly increased the plasma coagulation time and also exhibited reduced platelet adhesion and activation, thereby reducing the risk of blood coagulation and thrombosis.

Stress and Exposure Time on von Willebrand Factor Degradation.

Despite the prevailing use of the continuous flow left ventricular assist devices (cf-LVAD), acquired von Willebrand syndrome (AvWS) associated with cf-LVAD still remains a major complication. As AvWS is known to be dependent on shear stress (τ) and exposure time (t ), this study examined the degradation of high molecular weight multimers (HMWM) of von Willebrand factor (vWF) in terms of τ and t . Two custom apparatus, i.

Acquired Von Willebrand Syndrome and Blood Pump Design.

The existence of acquired von Willebrand syndrome (AVWS) in patients with continuous flow left ventricular assist devices (LVADs) is well documented and has been verified by numerous investigators. AVWS has not been observed to occur in pulsatile devices such as the SynCardia total artificial heart (TAH), the HeartMate XVE, and the Thoratec pulsatile ventricular assist device (PVAD) used as a single pump. AVWS can also occur in patients with aortic stenosis, ventricular septal defect, mitral stenosis, and patent ductus arteriosus.

Liquid Biopsy of Vitreous Reveals an Abundant Vesicle Population Consistent With the Size and Morphology of Exosomes.

Purpose: To investigate the molecular components of the vitreous in order to better understand retinal physiology and disease.

Methods: Vitreous was acquired from patients undergoing vitrectomy for macular hole and/or epiretinal membrane, postmortem donors, and C57BL/6J mice. Unbiased proteomic analysis was performed via electrospray ionization tandem mass spectrometry (MS/MS).

Reduction of Endothelial Nitric Oxide Increases the Adhesiveness of Constitutive Endothelial Membrane ICAM-1 through Src-Mediated Phosphorylation.

Nitric oxide (NO) is a known anti-adhesive molecule that prevents platelet aggregation and leukocyte adhesion to endothelial cells (ECs). The mechanism has been attributed to its role in the regulation of adhesion molecules on leukocytes and the adhesive properties of platelets. Our previous study conducted in rat venules found that reduction of EC basal NO synthesis caused EC ICAM-1-mediated firm adhesion of leukocytes within 10-30 min.

A new textured polyphosphazene biomaterial with improved blood coagulation and microbial infection responses.

Unlabelled: A new poly[bis(octafluoropentoxy) phosphazene] (OFP) was synthesized for the purpose of blood contacting medical devices. OFP was further either developed into crosslinkable polyphosphazene (X-OFP) or blended with polyurethane (PU) as the mixture (OFP/PU) for improvement of mechanical property of polyphosphazene polymers. All the materials were fabricated as smooth films or further textured with submicron pillars for the assay of antimicrobial and antithrombotic properties.

Interleukin-13 conjugated quantum dots for identification of glioma initiating cells and their extracellular vesicles.

Unlabelled: Cadmium selenide (CdSe) based quantum dots modified with polyethylene glycol and chemically linked to interleukin-13 (IL13) were prepared with the aim of identifying the high affinity receptor (IL13Rα2) which is expressed in glioma stem cells and exosomes secreted by these cancer stem cells. IL13 conjugated quantum dots (IL13QD) were thoroughly characterized for their physicochemical properties including particle size and surface morphology. Furthermore, the specific binding of the IL13QD to glioma cells and to glioma stem cells (GSC) was verified using a competitive binding study.