In vivo measurement of blood flow in a micro‐scale stenosis model generated by laser photothermal blood coagulation

Blood flow in a stenosed vessel is one of the most important issues, because it is closely related to the outbreak of circulatory diseases. To overcome the technological limitations encountered in the haemodynamic studies using in vitro stenosis models, the authors induced a stenosed flow model in the extraembryonic vessels of a chicken embryo. Blood was coagulated by laser irradiation to artificially form a stenosis on the designated spot in a straight blood vessel. Owing to photothermal coagulation of red blood cells (RBCs), the blood is denatured and a stable blood coagulum is induced in the vessel. The blood coagulum adheres firmly and stably on the vessel wall without any size variation. It disturbs the on‐coming blood flow significantly. To investigate the haemodynamic characteristics of the blood flow in the stenosed vessel, a micro particle image velocimetry technique was employed using RBCs as tracers to measure the spatial distributions of velocity vectors, streamlines and shear rate. The present simple modelling of in vivo stenosis would be useful for investigating the basic haemodynamic mechanisms underlying circulatory vascular diseases.Inspec keywords: adhesion, biological effects of laser radiation, biomedical optical imaging, blood, blood flow measurement, blood vessels, cellular biophysics, coagulation, diseases, flow visualisation, laser applications in medicine, photothermal effects, shear flowOther keywords: in vivo measurement, blood flow, microscale stenosis model, laser photothermal blood coagulation, stenosed vessel, circulatory diseases, haemodynamics, extraembryonic vessels, chicken embryo, laser irradiation, blood vessel, red blood cells, blood coagulum, adherence, vessel wall, microparticle image velocimetry, shear rate, circulatory vascular diseasesInspec keywords: adhesion, biological effects of laser radiation, biomedical optical imaging, blood, blood flow measurement, blood vessels, cellular biophysics, coagulation, diseases, flow visualisation, laser applications in medicine, photothermal effects, shear flowOther keywords: in vivo measurement, blood flow, microscale stenosis model, laser photothermal blood coagulation, stenosed vessel, circulatory diseases, haemodynamics, extraembryonic vessels, chicken embryo, laser irradiation, blood vessel, red blood cells, blood coagulum, adherence, vessel wall, microparticle image velocimetry, shear rate, circulatory vascular diseases     

The role of metal corrosion in inflammatory processes: induction of adhesion molecules by heavy metal ions

Prosthetic devices undergo corrosion processes after implantation including the release of certain amounts of metal ions into the adjacent tissues. On reaching the bloodstream, a systemic influence of those ions may be envisaged. Cell adhesion molecules (CAMs) are recognized as an essential component of the mechanisms of endothelial damage. To study the influence of selected heavy metals on human umbilical vein endothelial cells (HUVEC) EIA methods were used to evaluate cellular expression of E-selectin, ICAM-1, VCAM-1 and GMP-140 under the influence of high (cytotoxic) very low (non-cytotoxic) concentrations of Zn, Ni, Co and Cr. The de novo synthesis of CAMs was studied with the help of mRNA analysis. Intermediate voltage immuno electron-microscopical imaging was performed to detect the localization on the cell surface of the adhesion molecules E-selectin and ICAM-1 under the influence of cytokines, which represent important factors in inflammatory processes. Very low concentrations of metal ions, which gave no significant influence on cell morphology, elicited a significant expression of CAMs on endothelial cells in vitro. Thus, for example, zinc, nickel and cobalt ions in concentrations of 1×10^-9 M increased the expression of endothelial E-selectin, compared to the control after a 5 h incubation. Similar findings were established for zinc, nickel and cobalt ions also with regard to ICAM-1, VCAM-1 and GMP-140. Northern blot analysis gave an increased ELAM-1 and ICAM-1 mRNA expression after incubation with high concentrations of zinc and nickel ions. The results should draw attention to possible effects of very low concentrations, which are released during processes of metal corrosion on prosthetic devices.     

The role of newly formed vessels and cell adhesion molecules in the tissue response to wear products from orthopaedic implants

Neovascularization and activation of endothelial cells play an important role in recruitment of blood leucocytes at sites of inflammation. This study aimed to assess the pattern of vascular growth and the expression of cell adhesion molecules on vascular endothelium and inflammatory macrophages and T cells in the bone-implant interface from patients with aseptically loosened orthopaedic prostheses. ELAM-1, VCAM-1, ICAM-1 and the receptors LFA-1 and CR3 were immunolocalized on cryostat sections of the interface obtained during revision arthroplasty. The results showed that ELAM-1 was restricted to endothelium and was upregulated on different vessels in 21 cases. Its expression correlated strongly with the presence of metal wear debris. VCAM-1 was less frequently expressed (n=6 cases), and was co-expressed with ELAM-1 in three cases with metal debris. ICAM-1 was detected on a large number of vessels on the bone side in 13 cases, but was more strongly expressed on macrophage subsets and foreign body giant cells (FBGCs) on the lining layer at the implant side. This study indicates the contribution of three different pathways in the migration of inflammatory cells to the bone-implant interface in response to phagocytosis of implant degradation products. Upregulated ELAM-1 expression may suggest a role in hypersensitivity reactions. Finally the persistent expression of VCAM-1 and ICAM-1 on macrophages and FBGCs in the lining layer indicates possible cellular interactions with the extracellular matrix proteins.     

Arterial pulse wave propagation across stenoses and aneurysms: assessment of one-dimensional simulations against three-dimensional simulations and in vitro measurements

One-dimensional (1-D) arterial blood flow modelling was tested in a series of idealized vascular geometries representing the abdominal aorta, common carotid and iliac arteries with different sizes of stenoses and/or aneurysms. Three-dimensional (3-D) modelling and in vitro measurements were used as ground truth to assess the accuracy of 1-D model pressure and flow waves. The 1-D and 3-D formulations shared identical boundary conditions and had equivalent vascular geometries and material properties. The parameters of an experimental set-up of the abdominal aorta for different aneurysm sizes were matched in corresponding 1-D models. Results show the ability of 1-D modelling to capture the main features of pressure and flow waves, pressure drop across the stenoses and energy dissipation across aneurysms observed in the 3-D and experimental models. Under physiological Reynolds numbers (Re), root mean square errors were smaller than 5.4% for pressure and 7.3% for the flow, for stenosis and aneurysm sizes of up to 85% and 400%, respectively. Relative errors increased with the increasing stenosis and aneurysm size, aneurysm length and Re, and decreasing stenosis length. All data generated in this study are freely available and provide a valuable resource for future research.     

Peptide-Functionalized Prussian Blue Nanomaterial for Antioxidant Stress and NIR Photothermal Therapy against Alzheimer's Disease

Excessive accumulations of reactive oxygen species (ROS) and amyloid-β (Aβ) protein are closely associated with the complex pathogenesis of Alzheimer's disease (AD). Therefore, approaches that synergistically exert elimination of ROS and dissociation of Aβ fibrils are effective therapeutic strategies for correcting the AD microenvironment. Herein, a novel near infrared (NIR) responsive Prussian blue-based nanomaterial (PBK NPs) is established with excellent antioxidant activity and photothermal effect. PBK NPs possess similar activities to multiple antioxidant enzymes, including superoxide dismutase, peroxidase, and catalase, which can eliminate massive ROS and relieve oxidative stress. Under the NIR irradiation, PBK NPs can generate local heat to disaggregate Aβ fibrils efficiently. By modifying CKLVFFAED peptide, PBK NPs display obvious targeting ability for blood–brain barrier penetration and Aβ binding. Furthermore, in vivo studies demonstrate that PBK NPs have outstanding ability to decompose Aβ plaques and alleviate neuroinflammation in AD mouse model. Overall, PBK NPs provide evident neuroprotection by reducing ROS levels and regulating Aβ deposition, and may accelerate the development of multifunctional nanomaterials for delaying the progression of AD.     

Three-dimensional periodic structures of gold nanoclusters in the interstices of sub-100 nm polymer particles toward surface-enhanced Raman scattering

Regularly ordered polymer nanoparticle (PNP) assemblies incorporating gold nanoparticle (Au NP) clusters into the PNP interstices were fabricated by a simultaneous deposition of PNPs and Au NPs on a glass substrate. Monodisperse PNPs with an average size of 66 nm were employed as a template in the co-assembly to create the sub-100 nm periodic Au nanostructures on the substrate. First, mono-layering of PNP array with incorporation of 14 nm Au NPs was performed by a drop-casting to examine the number ratio of Au NPs to PNPs for multi-layering. Absorption spectra of the mono-layered co-assemblies of PNPs and Au NPs were employed to characterize the clustered state of Au NPs in the interstices of mono-layered PNPs. The number ratio suitable for homogeneous incorporation of Au NPs clustered in the interstice was found to be ranged from 6 to 8 in the characterization. Then, multi-layered co-assemblies of PNPs and clustered Au NPs were fabricated by a vertical deposition method with the Au NP number ratio of 8 to PNPs. Lifting rate of the substrate on which the PNPs were deposited was varied in the vertical deposition method to tune the film thickness of NP co-assembly. A decrease in the lifting rate to 1 μm/s could thicken the film to 0.71 μm corresponding to 13 layers of PNPs, resulting in the fabrication of periodic structures of Au NP clusters with a high packing density. Signal-to-noise ratio in the Raman measurement using p-mercaptobenzoic acid as a target molecule was successfully enhanced by multi-layering of the co-assembly, indicating that Au NP clusters were homogeneously incorporated into the interstices of PNPs in the co-assemblies.     

Blood flow dynamics reflect degree of outflow tract banding in Hamburger–Hamilton stage 18 chicken embryos

Altered blood flow during embryonic development has been shown to cause cardiac defects; however, the mechanisms by which the resulting haemodynamic forces trigger heart malformation are unclear. This study used heart outflow tract banding to alter normal haemodynamics in a chick embryo model at HH18 and characterized the immediate blood flow response versus the degree of band tightness. Optical coherence tomography was used to acquire two-dimensional longitudinal structure and Doppler velocity images from control (n = 16) and banded (n = 25, 6–64% measured band tightness) embryos, from which structural and velocity data were extracted to estimate haemodynamic measures. Peak blood flow velocity and wall shear rate (WSR) initially increased linearly with band tightness (p < 0.01), but then velocity plateaued between 40% and 50% band tightness and started to decrease with constriction greater than 50%, whereas WSR continued to increase up to 60% constriction before it began decreasing with increased band tightness. Time of flow decreased with constriction greater than 20% (p < 0.01), while stroke volume in banded embryos remained comparable to control levels over the entire range of constriction (p > 0.1). The haemodynamic dependence on the degree of banding reveals immediate adaptations of the early embryonic cardiovascular system and could help elucidate a range of cardiac adaptations to gradually increased load.     

Association between erythrocyte dynamics and vessel remodelling in developmental vascular networks

Sprouting angiogenesis is an essential vascularization mechanism consisting of sprouting and remodelling. The remodelling phase is driven by rearrangements of endothelial cells (ECs) within the post-sprouting vascular plexus. Prior work has uncovered how ECs polarize and migrate in response to flow-induced wall shear stress (WSS). However, the question of how the presence of erythrocytes (widely known as red blood cells (RBCs)) and their impact on haemodynamics affect vascular remodelling remains unanswered. Here, we devise a computational framework to model cellular blood flow in developmental mouse retina. We demonstrate a previously unreported highly heterogeneous distribution of RBCs in primitive vasculature. Furthermore, we report a strong association between vessel regression and RBC hypoperfusion, and identify plasma skimming as the driving mechanism. Live imaging in a developmental zebrafish model confirms this association. Taken together, our results indicate that RBC dynamics are fundamental to establishing the regional WSS differences driving vascular remodelling via their ability to modulate effective viscosity.     

Growth of ZnO nanorods on TiO2 nanoparticles films and their application to the electrode of dye-sensitized solar cells

A ZnO nanorods (NRs)/TiO₂ nanoparticles (NPs) film has been prepared by electrochemical deposition of ZnO NRs growth on P25 TiO₂ NPs film surfaces. It was found that ZnO NRs/TiO₂ NPs could significantly improve the efficiency of dye-sensitized solar cells owing to its relatively enhanced light-scattering capability and efficient charge transport efficiency. The overall energy-conversion efficiency (η) of 3.48 % was achieved by the formation of ZnO NRs/TiO₂ NPs film, which is 33 % higher than that formed by TiO₂ NPs alone (η = 2.62 %). The charge recombination behavior of cells was investigated by electrochemical impedance spectra, and the results showed that ZnO NRs/TiO₂ NPs film has the longer electron lifetime than TiO₂ NPs alone, which could facilitate the reduction of recombination processes and thus would promote the photocatalysis and solar cell performance.     

Hydrodynamic description of CVD processes

A CVD process with a two-component gas mixture A-B where only the component B is deposited is solved numerically for an axisymmetric stagnation flow geometry assuming the mass function of B on the deposition surface to have a fixed value Y_Bd. A comparison of the calculated flow lines with visualization experiments shows satisfactory agreement. The agreement between calculations and SiO₂ and Si₃N₄ deposition experiments (SiH₄ + O₂ → SiO₂, SiH₄ + NH₃ → Si₃N₄) was good for some deposition ranges. In these ranges the deposition profiles could be calculated with only one fitting parameter (Y_Bd).     

Stent strut streamlining and thickness reduction promote endothelialization

Stent thrombosis (ST) carries a high risk of myocardial infarction and death. Lack of endothelial coverage is an important prognostic indicator of ST after stenting. While stent strut thickness is a critical factor in ST, a mechanistic understanding of its effect is limited and the role of haemodynamics is unclear. Endothelialization was tested using a wound-healing assay and five different stent strut models ranging in height between 50 and 150 µm for circular arc (CA) and rectangular (RT) geometries and a control without struts. Under static conditions, all stent strut surfaces were completely endothelialized. Reversing pulsatile disturbed flow caused full endothelialization, except for the stent strut surfaces of the 100 and 150 µm RT geometries, while fully antegrade pulsatile undisturbed flow with a higher mean wall shear stress caused only the control and the 50 µm CA geometries to be fully endothelialized. Modest streamlining and decrease in height of the stent struts improved endothelial coverage of the peri-strut and stent strut surfaces in a haemodynamics dependent manner. This study highlights the impact of the stent strut height (thickness) and geometry (shape) on the local haemodynamics, modulating reendothelialization after stenting, an important factor in reducing the risk of stent thrombosis.     

Computer simulations reveal complex distribution of haemodynamic forces in a mouse retina model of angiogenesis

There is currently limited understanding of the role played by haemodynamic forces on the processes governing vascular development. One of many obstacles to be overcome is being able to measure those forces, at the required resolution level, on vessels only a few micrometres thick. In this paper, we present an in silico method for the computation of the haemodynamic forces experienced by murine retinal vasculature (a widely used vascular development animal model) beyond what is measurable experimentally. Our results show that it is possible to reconstruct high-resolution three-dimensional geometrical models directly from samples of retinal vasculature and that the lattice-Boltzmann algorithm can be used to obtain accurate estimates of the haemodynamics in these domains. We generate flow models from samples obtained at postnatal days (P) 5 and 6. Our simulations show important differences between the flow patterns recovered in both cases, including observations of regression occurring in areas where wall shear stress (WSS) gradients exist. We propose two possible mechanisms to account for the observed increase in velocity and WSS between P5 and P6: (i) the measured reduction in typical vessel diameter between both time points and (ii) the reduction in network density triggered by the pruning process. The methodology developed herein is applicable to other biomedical domains where microvasculature can be imaged but experimental flow measurements are unavailable or difficult to obtain.     

A substance flow analysis in the southern hemisphere: cadmium in the Australian economy

This article analyses the flow of cadmium through the Australian economy during the one-year period, 1998–1999 using material flow analysis (MFA) or substance flow analysis (SFA) as a framework. MFA/SFA can provide a holistic picture of resource use and loss through a geographic region in a specific year, allowing all material/substance inflows, outflows, and stocks through each sub-compartment in the economy to be examined. The results of the study were visualized and presented in diagrams, including an aggregate diagram of the economic system. Existing data from a large variety of sources was utilised to complete all cadmium flows within the Australian economy. Some assumptions and judgments were made in order to determine the cadmium flows in each operation and application stage. Australian cadmium sources are linked to the resources of zinc, lead, copper, iron, limestone and gypsum. A large accumulation of cadmium can result from on-site waste treatment arising from industrial facilities and household-waste landfills. Atmospheric deposition, phosphate fertilisers and animal manure have been identified as other significant inputs to agricultural soils, especially at some polluted areas near industrial facilities. The measurement, analysis and control of the cadmium flows in Australia are therefore considered on the basis of these abundant resources, certain commodities and agricultural inputs. The SFA analysis presented is a useful tool in the development of a cadmium management policy suited to the Australian economy and the receiving environment.     

Motion and deposition of non-brownian particles in upflow collectors

The motion and deposition of suspended particles in upflow unit cells of sinusoidal shape are studied using a three-dimensional trajectory analysis. Particle stagnation and exclusion regions can develop at the entrance mouth of upflow cells, the extent and distribution of which depend on several parameters including particle size, flow rate, cell geometry, and cell inclination. It is found that the particle exclusion phenomenon can become very significant over a wide range of the preceding parameters and can have significant implications in network-based simulations of upflow or horizontal flow depth filtration. A new definition of the impacted fraction is introduced that is based on the particle entrance velocity and the actual entrance region. Calculations of the deposition rate in sinusoidal collectors indicate that switching from a downflow to an upflow mode results in increased or decreased capture efficiency depending, chiefly, on the inclination of the unit collector.     

Conjugation of membrane-destabilizing peptide onto gelatin–siloxane nanoparticles for efficient gene expression

One of the crucial steps in gene delivery with non-viral vectors is the escape of DNA complexes from the endosome. In order to improve gene transfection efficiency, we designed a novel gene delivery vector gelatin–siloxane nanoparticles (GS NPs) conjugated with two different membrane-destabilizing peptides, octaarginine (R8) and a subunit of influenza virus haemagglutinin HA2. Both R8-GS NPs and HA2-GS NPs had high positive surface charges. They could condense and protect DNA against serum/DNase degradation. Results from flow cytometry and confocal laser scanning microscope respectively indicated that R8-GS NPs had higher uptake efficiency than HA2-GS NPs, whereas HA2-GS had higher endosome escaping efficiency. Furthermore, in vitro transfection displayed a higher gene expression level with HA2-modified GS NPs, which suggested that endosome escaping is the crucial step for nanoparticle mediated gene therapy.     

Effect of rapid thermal annealing time on Au/SiOx film prepared by hot wire assisted plasma enhanced chemical vapour deposition technique

In this study, nanocomposite material consisting of silicon suboxide (SiO_x) film embedded with gold nanoparticles (Au NPs) was synthesized using hybrid technique combining hot wire evaporation and plasma enhanced chemical vapour deposition (PECVD) method. As prepared Au/SiO_x films were rapid thermal annealed at constant temperature of 800 °C for different annealing times from 30 to 120 s. The use of tungsten filament for Au evaporation allowed the effective reduction of the silicon content. Depth profiling analysis confirmed the embedded in structure of Au/SiO_x film. FESEM, UV/VIS/NIR and PL spectroscopy were utilized to study the structural and optical properties of annealed Au/SiO_x film for different times. Embedded Au NPs diffused towards the surface of SiO_x film agglomerate and increased in size with an increase in annealing time. Localized surface plasmon resonance (LSPR) peak induced by Au NPs in SiO_x, which is dependent on annealing time, was clearly observed in optical spectra. Intensity and position of the PL peak located at 580 nm experienced a decrease and red-shift, as annealing time increased.     

Detection of β‐Amyloid by Sialic Acid Coated Bovine Serum Albumin Magnetic Nanoparticles in a Mouse Model of Alzheimer's Disease

The accumulation and formation of β‐amyloid (Aβ) plaques in the brain are distinctive pathological hallmarks of Alzheimer's disease (AD). Designing nanoparticle (NP) contrast agents capable of binding with Aβ highly selectively can potentially facilitate early detection of AD. However, a significant obstacle is the blood brain barrier (BBB), which can preclude the entrance of NPs into the brain for Aβ binding. In this work, bovine serum albumin (BSA) coated NPs are decorated with sialic acid (NP‐BSA_x‐Sia) to overcome the challenges in Aβ imaging in vivo. The NP‐BSA_x‐Sia is biocompatible with high magnetic relaxivities, suggesting that they are suitable contrast agents for magnetic resonance imaging (MRI). The NP‐BSA_x‐Sia binds with Aβ in a sialic acid dependent manner with high selectivities toward Aβ deposited on brains and cross the BBB in an in vitro model. The abilities of these NPs to detect Aβ in vivo in human AD transgenic mice by MRI are evaluated without the need to coinject mannitol to increase BBB permeability. T₂*‐weighted MRI shows that Aβ plaques in mouse brains can be detected as aided by NP‐BSA_x‐Sia, which is confirmed by histological analysis. Thus, NP‐BSA_x‐Sia is a promising new tool for noninvasive in vivo detection of Aβ plaques.     

ZnO nanorods arrays with Ag nanoparticles on the (002) plane derived by liquid epitaxy growth and electrodeposition process

Well-aligned ZnO nanorods (NRs) arrays with Ag nanoparticles (NPs) on the (002) plane are obtained by combining a liquid epitaxy technique with an electrodeposition process. Cyclic voltammetry study is employed to understand the electrochemical behaviors of the electrodeposition system, and potentiostatic method is employed to deposit silver NPs on the ZnO NRs in the electrolyte with an Ag⁺ concentration of 1 mM. X-ray diffraction analysis is used to study the crystalline properties of the as-prepared samples, and energy dispersive X-ray is adopted to confirm the composition at the surface of the deposited samples. Results indicate only a small quantity of silver can be deposited on the surface of the samples. Effect of the deposition potential and time on the morphological properties of the resultant Ag NPs/ZnO NRs are investigated in detail. Scanning electron microscopy images and transmission electron microscopy images indicate that the Ag NPs deposited on the (002) plane of the ZnO NRs with a large dispersion in diameter can be obtained by a single potentiostatic deposition process, while dense Ag NPs with a much smaller diameter dispersion on the top of the ZnO NRs, most of which locate on the conical tip of the ZnO NRs, can be obtained by a two-potentiostatic deposition process, The mechanism of this deposition process is also suggested.