Scanning Laser Doppler Research Articles

The selective PAC1 receptor agonist maxadilan inhibits neurogenic vasodilation and edema formation in the mouse skin

We have earlier shown that PACAP-38 decreases neurogenic inflammation. However, there were no data on its receptorial mechanism and the involvement of its PAC1 and VPAC1/2 receptors (PAC1R, VPAC1/2R) in this inhibitory effect.Neurogenic inflammation in the mouse ear was induced by topical application of the Transient Receptor Potential Ankyrin 1 (TRPA1) receptor activator mustard oil (MO). Consequent neurogenic edema, vasodilation and plasma leakage were assessed by measuring ear thickness with engineer's micrometer, detecting tissue perfusion by laser Doppler scanning and Evans blue or indocyanine green extravasation by intravital videomicroscopy or fluorescence imaging, respectively. Myeloperoxidase activity, an indicator of neutrophil infiltration, was measured from the ear homogenates with spectrophotometry. The selective PAC1R agonist maxadilan, the VPAC1/2R agonist vasoactive intestinal polypeptide (VIP) or the vehicle were administered i.p. 15 min before MO. Substance P (SP) concentration of the ear was assessed by radioimmunoassay.Maxadilan significantly diminished MO-induced neurogenic edema, increase of vascular permeability and vasodilation. These inhibitory effects of maxadilan may be partially due to the decreased substance P (SP) levels. In contrast, inhibitory effect of VIP on ear swelling was moderate, without any effect on MO-induced plasma leakage or SP release, however, activation of VPAC1/2R inhibited the increased microcirculation caused by the early arteriolar vasodilation. Neither the PAC1R, nor the VPAC1/2R agonist influenced the MO-evoked increase in tissue myeloperoxidase activity.These results clearly show that PAC1R activation inhibits acute neurogenic arterial vasodilation and plasma protein leakage from the venules, while VPAC1/2R stimulation is only involved in the attenuation of vasodilation.

Spectral domain optical coherence tomography used to view and quantify choroidal vascular congestion in new subretinal fluid following encircling scleral buckling

Known complications of scleral buckling surgery for primary rhegmatogenous retinal detachment include choroidal detachment, vortex vein compression and anterior segment ischemia. Post-operative persistent subretinal fluid following scleral buckling surgery is thought to occur in as many as 55% of cases. Likely mechanisms include impaired retinal pigment epithelium (RPE) function, altered subretinal fluid composition, choroidal ischemia, incomplete drainage of subretinal fluid and altered choroidal blood flow. Indocyanine green (ICG) angiography, laser Doppler velocimetry and scanning laser Doppler flowmetry have showed altered choroidal blood flow, pulsatile ocular blood flow and choroidal venous drainage after scleral buckling.

From nanospheres to microribbons: Self-assembled Eosin Y doped PMMA nanoparticles as photonic crystals

A modified emulsion synthesis of poly(methylmethacrylate) (PMMA) with the Eosin Y (EY), commercial chromophore, yields dye doped polymeric nanoparticles (PMMA@EY). A systematic investigation on the experimental parameters (monomer and initiator concentration, reaction time and MMA/EY molar ratio) has been explored to modulate physico-chemical properties of the dye doped polymeric colloids. Spherical shaped particles, doped with EY (0.5–3.0wt%; loading efficiency η=11–15%), with controlled diameters in the range 240–510nm, low dispersity and ζ-potential values in the range between −42mV and −59mV, have been synthesized and characterized by means of UV–Vis spectrometry, Dynamic Light Scattering (DLS), laser Doppler electrophoresis and Scanning Electron Microscopy (SEM). Microribbons based on PMMA@EY nanoparticles have been fabricated by room temperature self-assembly of aqueous colloidal suspension on highly wettable glass substrates. Surface chemical treatment assisted the formation of long (up to few centimeters) regular ribbons with rectangular section. Lateral size and height of the structures have been controlled by changing the suspension concentration and/or the deposition volume: the higher suspension concentration produces larger and thicker ribbons and the higher deposited volume produces thicker ribbons (up to 23μm with 198μL of a 3wt% suspension). Moreover, a transition from a film-like to a ribbon-like growth has been observed with increasing nanoparticles concentration. Short range ordering and photonic crystal features have been maintained in the fluorescent ribbon microarchitecture, resulting in a self-assembled material with excellent potential for the development of mirror-less and random lasers.

Mechanical frequency selectivity of an artificial basilar membrane using a beam array with narrow supports

The study presented in this paper assessed the frequency selectivity of an artificial basilar membrane (ABM) constructed using a piezoelectric beam array with narrow supports. Three ABM samples were constructed. Each ABM contained 16 beams with various lengths in a one-dimensional array. To experimentally assess the frequency selectivity of the ABM, mechanical vibration induced either by an electrical or an acoustic stimulus was measured with a scanning laser-Doppler vibrometer. The electro-mechanical and acousto-mechanical transfer functions were defined for the same purpose. The tonotopy of each beam array was visualized by post-processing the experimental results. Finite element analyses were conducted to numerically compute the resonance frequencies, identify the associated vibrational modes, and evaluate the harmonic responses of the beams. The influence of the residual stresses existing in the beams was reflected in the geometric models by introducing three different levels of arc-shaped lateral deformations in the beams. The harmonic analyses revealed that each beam of the ABM samples presented independent band-pass characteristics. The experiments and simulations commonly showed a frequency selectivity of the fabricated ABMs in the range of 2–20 kHz. Therefore, the device is suitable for development of a totally implantable artificial cochlea, implementing a mechanical frequency analyzer. This work is part of research to develop a prototype of a totally implantable artificial cochlea.

Characterising neovascularisation in fracture healing with laser Doppler and micro-CT scanning

Vascularity of the soft tissues around a bone fracture is critical for successful healing, particularly when the vessels in the medullary canal are ruptured. The objective of this work was to use laser Doppler and micro-computer tomography (micro-CT) scanning to characterise neovascularisation of the soft tissues surrounding the fracture during healing. Thirty-two Sprague–Dawley rats underwent mid-shaft osteotomy of the left femur, stabilised with a custom-designed external fixator. Five animals were killed at each of 2, 4 days, 1, 2, 4 and 6 weeks post-operatively. Femoral blood perfusion in the fractured and intact contralateral limbs was measured using laser Doppler scanning pre- and post-operatively and throughout the healing period. At sacrifice, the common iliac artery was cannulated and infused with silicone contrast agent. Micro-CT scans of the femur and adjacent soft tissues revealed vessel characteristics and distribution in relation to the fracture zone. Blood perfusion dropped immediately after surgery and then recovered to greater than the pre-operative level by proliferation of small vessels around the fracture zone. Multi-modal imaging allowed both longitudinal functional and detailed structural analysis of the neovascularisation process.

Laser-scanning Doppler photoacoustic microscopy based on temporal correlation

We present a methodology to measure absolute flow velocity using laser-scanning photoacoustic microscopy. To obtain the Doppler angle, the angle between ultrasonic detection axis and flow direction, we extracted the distances between the transducer and three adjacent scanning points along the flow and repeatedly applied the law of cosines. To measure flow velocity along the ultrasonic detection axis, we calculated the time shift between two consecutive photoacoustic waves at the same scanning point, then converted the time shift to velocity according to the sound velocity and time interval between two laser illuminations. We verified our method by imaging flow phantoms.

Damage localisation in a stiffened plate structure using a propagating wave

The paper presents an application of changes in propagating waves for damage detection in a stiffened aluminium plate. The experimental investigation was conducted on an aluminium plate with riveted two L-shape stiffeners. The wave has been excited with a piezoelectric transducer and measured with the Laser Scanning Doppler Vibrometer. Recorded signals were analysed using the special signal processing techniques developed for damage detection. The influence of different wave signals on damage localisation process for various damage scenarios has been tested. The obtained results were presented in a form of numerical maps. It may be concluded that the proposed approach enables damage localisation in a relatively fast and precise manner.

Structural resonance and mode of flutter of hummingbird tail feathers

Feathers can produce sound by fluttering in airflow. This flutter is hypothesized to be aeroelastic, arising from the coupling of aerodynamic forces to one or more of the feather's intrinsic structural resonance frequencies. We investigated how mode of flutter varied among a sample of hummingbird tail feathers tested in a wind tunnel. Feather vibration was measured directly at ~100 points across the surface of the feather with a scanning laser Doppler vibrometer (SLDV), as a function of airspeed, Uair. Most feathers exhibited multiple discrete modes of flutter, which we classified into types including tip, trailing vane and torsional modes. Vibratory behavior within a given mode was usually stable, but changes in independent variables such as airspeed or orientation sometimes caused feathers to abruptly 'jump' from one mode to another. We measured structural resonance frequencies and mode shapes directly by measuring the free response of 64 feathers stimulated with a shaker and recorded with the SLDV. As predicted by the aeroelastic flutter hypothesis, the mode shape (spatial distribution) of flutter corresponded to a bending or torsional structural resonance frequency of the feather. However, the match between structural resonance mode and flutter mode was better for tip or torsional mode shapes, and poorer for trailing vane modes. Often, the 3rd bending structural harmonic matched the expressed mode of flutter, rather than the fundamental. We conclude that flutter occurs when airflow excites one or more structural resonance frequencies of a feather, most akin to a vibrating violin string.

Vascular endothelial growth factor-C derived from CD11b+ cells induces therapeutic improvements in a murine model of hind limb ischemia

The use of bone marrow cells (BMCs) in therapeutic angiogenesis has been studied extensively. However, the critical paracrine effects of this treatment are still unclear. Therefore, we studied autotransfusable cells that produce vascular endothelial growth factor (VEGF), especially VEGF-C. Male C57BL/6 mice with hind limb ischemia were administered intramuscular injections of phosphate-buffered saline as controls, or unsorted BMCs, sorted CD11b(+), or CD11b(-) cells from BMCs, and recombinant VEGF-C. To evaluate the treatments, perfusion was measured by laser Doppler scanning performed on days 0, 1, 3, 7, 14, 21, and 28. A functional assay was performed in parallel, with mice traversing an enclosed walkway. Capillary density was determined by directly counting vessels stained positive with von Willebrand factor at individual time points. Lymphangiogenesis was assessed by LYVE-1 positive cells. Postischemic recovery of hind limb perfusion significantly improved in BMC, CD11b(+), and VEGF-C treatment groups compared with the control groups, as assessed by laser Doppler scanning. On early operative days 1 and 3, the blood flow recovery ratio was higher in the CD11b(+)-treated group compared with BMC and VEGF-C treatment groups. In the functional assay, the VEGF-C group dramatically recovered compared with the control group. The capillary/myofiber ratio in the thigh muscle and number of LYVE-1 positive cells was higher in the CD11b(+) and VEGF-C groups than in controls. Furthermore, expression of VEGF-A, VEGF-C, and VEGF receptor messenger ribonucleic acid and protein was observed in CD11b(+) cells. The VEGF-C derived from CD11b(+) cells play a critical role in angiogenesis and lymphangiogenesis in a murine model of hind limb ischemia. Consequently, treatment with self-CD11b(+) cells accelerated recovery from ischemia and may be a promising therapeutic strategy for peripheral arterial disease patients.

Impact of obesity control on circulating level of endothelial progenitor cells and angiogenesis in response to ischemic stimulation

Background and aimWe tested the hypothesis that obesity reduced circulating number of endothelial progenitor cells (EPCs), angiogenic ability, and blood flow in ischemic tissue that could be reversed after obesity control.Methods8-week-old C57BL/6J mice (n = 27) were equally divided into group 1 (fed with 22-week control diet), group 2 (22-week high fat diet), and group 3 (14-week high fat diet, followed by 8-week control diet). Critical limb ischemia (CLI) was induced at week 20 in groups 2 and 3. The animals were sacrificed at the end of 22 weeks.ResultsHeart weight, body weight, abdominal fat weight, serum total cholesterol level, and fasting blood sugar were highest in group 2 (all p < 0.001). The numbers of circulating EPCs (C-kit/CD31+, Sca-1/KDR + and CXCR4/CD34+) were lower in groups 1 and 2 than in group 3 at 18 h after CLI induction (p < 0.03). The numbers of differentiated EPCs (C-kit/CD31+, CXCR4/CD34+ and CD133+) from adipose tissue after 14-day cultivation were also lowest in group 2 (p < 0.001). Protein expressions of VCAM-1, oxidative index, Smad3, and TGF-β were higher, whereas the Smad1/5 and BMP-2, mitochondrial cytochrome-C SDF-1α and CXCR4 were lower in group 2 than in groups 1 and 3 (all p < 0.02). Immunofluorescent staining of CD31+ and vWF + cells, the number of small vessel (<15 μm), and blood flow through Laser Doppler scanning of ischemic area were lower in group 2 compared to groups 1 and 3 on day 14 after CLI induction (all p < 0.001).ConclusionObesity suppressed abilities of angiogenesis and recovery from CLI that were reversed by obesity control.

Abstract 120: Reversal of Nox 4-Induced Oxidative Stress in Type 2 Diabetic Mesenchymal Stem Cells Restores Their Capacity to Augment Postischemic Neovascularization in db/db Mice

Rationale: We have recently shown that experimental type 2 diabetes (db/db mouse) restricts mesenchymal stem cell’ (MSCs) differentiation capacity through a hyperinsulinemia-dependent induction of Nox 4 expression that promotes adipocytic and inhibits endothelial cell differentiation both in vitro and in vivo. We also showed that transplantation of type 2 diabetic MSCs into wild type (WT) recipients reduced post-ischemic neovascularization significantly below that of WT recipients receiving WT MSCs. Objective: This study tested the hypothesis that pretreatment of db/db MSCs with siRNA Nox4 prior to their transplantation and infusion 24 hrs after the induction of hindlimb ischemia restores their differentiation capacity in vivo and rescues their impaired capacity to promote neovascularization in wild type mice. Methods and Results: To reverse oxidative stress in db/db MSCs, we knockdown NOX 4 expression by a siRNA under in vitro conditions. In vitro inhibition of Nox 4 expression of db/db MSCs significantly increased their differentiation capacity towards endothelial cells and reduced their propensity to differentiate into adipocytes. Db/db MSCs also showed significantly increased tubular formation ability after Nox 4 knockdown. We transplanted NOX 4 siRNA transduced db/db MSCs into WT recipients 24 hours after induction of hindlimb ischemia. Blood flow recovery was measured at different time points by laser Doppler scanning. Reversal of oxidative stress in db/db MSCs by pretreatment with Nox4 siRNA prior to transplantation reversed their impaired capacity to augment post-ischemic neovascularization as evidenced by blood flow recovery that increased to that of WT mice. In addition, knockdown of NOX 4 expression in db/db MSCs also increased collateral artery diameter and capillary density by 50%. Conclusions: Pretreatment of db/db MSCs with siRNA against Nox 4 significantly increased their differentiation capacity towards endothelial cells rather than adipocytes and also their capacity to augment neovascularization after induction of hindlimb ischemia. Reversal of MSC oxidant stress induced by type 2 diabetes might permit greater leverage of the therapeutic potential of MSC transplantation to treat cardiovascular diseases.

Increased stability of S-nitrosothiol solutions via pH modulations

S-nitrosothiol (RSNO) solutions represent a valuable source of nitric oxide and could be used as topical vasodilators, but their fast decomposition rate poses a serious obstacle to their potentially widespread therapeutic use. Our aim was to characterize and quantify the effect of pH on S-nitrosothiol formation and decomposition in simple aqueous solutions of S-nitrosoglutathione (GSNO), S-nitroso-N-acetylcysteine (SNAC) and S-nitroso-3-mercaptopropionic acid (SN3MPA). Furthermore, we investigated the effect of storage pH on the stability of GSNO incorporated in poly(ethylene glycol)/ poly(vinyl alcohol) matrices. S-nitrosothiol concentrations were measured spectrophotometrically and laser Doppler scanning method was used to assess dermal blood flow. GSH and NAC solutions reached a complete transformation to nitrosothiols when synthesized using acidic NaNO2 solution. The initial concentration of all investigated RSNOs decreased more slowly with pH adjusted to mildly basic values (8.4–8.8) for the storage period. Polymer gels of PVA/PEG compositions at mildly basic storage pH further reduced the decomposition rate succeeding to contain 46.8% of the initial GSNO concentration for 25 days. This amount of topically administered GSNO was still capable of increasing the dermal blood flow over 200% in human subjects.

Abstract 17275: Induction of Arteriogenesis in Mouse Hindlimb by Human Peripheral Blood B Cells as Determined by Micro-CT Imaging

For patients with critical limb ischemia, restoration of blood flow through mechanical or pharmacological revascularization is an important therapeutic goal. Clinical studies have been unsuccessful in enhancement of neovascularization by treatment with angiogenic growth factors. We have shown that bone marrow derived B cells delivered into rat ischemic myocardium preserves cardiac function (Goodchild et al, 2009) and we sought to determine if B cells could be therapeutically beneficial in a mouse model of critical limb ischemia. Since commonly used histological determination of angiogenesis only provides semi-quantitative measure of vessels in limited tissue area without confirming perfusion functionality, this study measured the angiogenic and arteriogenic activities of B cell therapy using high resolution computed tomography. Mice (n=16, Balb/c) had iliac and femoral arteries and veins ligated. Mouse bone marrow B cells (CD19+) isolated by antibody-magnetic bead selection or saline control was injected directly into ischemic muscles. A post-ligation laser Doppler scan was performed to ensure ligation consistency then scanned weekly. On Day 28, mice were euthanized, vasculature flushed, fixed and perfused with contrast agent. Limbs were imaged by micro-CT with reconstruction at 25um. Data represented as vascular segment number and area counted in 500 slices in 3D micro-CT images. At Days 7, 14, 21 and 28, blood flow increased in B cell treated ischemic hindlimbs compared to controls. At Day 28, B cell treatment increased number of vessels in treated-ligated legs compared to unligated legs (8033±439 vs. 5297±710 vessels, respectively; P=0.010) and vessel area (175.9±45.4 vs. 99.0±28.6 mm2, respectively; P=0.012). Vessels ranging from 25-175 and 225-350um were increased in B cell treated-ligated legs compared to unligated legs (P&lt;0.05). Vessel number ratio in treated-ligated legs to unligated legs was higher in B cell treated compared to control treated mice (1.66 vs. 1.05; P=0.025). These data show that unlike angiogenic response to treatment with growth factors, B cells enhanced development of vessels with a wide range of diameters suggesting that B cells may offer therapeutic potential for treatment of ischemic peripheral artery disease.

Application of RMS for damage detection by guided elastic waves

This paper presents certain results of an experimental study related with a damage detection in structural elements based on deviations in guided elastic wave propagation patterns. In order to excite guided elastic waves within specimens tested piezoelectric transducers have been applied. As excitation signals 5 sine cycles modulated by Hanning window have been used. Propagation of guided elastic waves has been monitored by a scanning Doppler laser vibrometer. The time signals recorded during measurement have been utilised to calculate the values of RMS. It has turned out that the values of RMS differed significantly in damaged areas from the values calculated for the healthy ones. In this way it has become possible to pinpoint precisely the locations of damage over the entire measured surface. All experimental investigations have been carried out for thin aluminium or composite plates. Damage has been simulated by a small additional mass attached on the plate surface or by a narrow notch cut. It has been shown that proposed method allows one to localise damage of various shapes and sizes within structural elements over the whole area under investigation.

Laser Doppler perfusion imaging in systemic sclerosis impaired response to cold stimulation involves digits and hand dorsum

To assess by Laser Doppler perfusion imaging (LDPI) skin blood perfusion of hands in patients with SSc and primary RP (PRP) at baseline and after cold stimulation (CS). In SSc patients, the associations between skin perfusion and nailfold video capillaroscopy (NVC) patterns were also evaluated. Forty patients with SSc, 38 patients with PRP and 32 healthy controls were recruited. Skin blood flow of the hands was detected by Lisca Laser Doppler Perfusion Imager at baseline and after CS. Further laser Doppler scanning was performed for each hand at 0 (T(1)), 3 (T(2)), 7 (T(3)) and 15 min (T(4)). Baseline mean perfusion is significantly (P < 0.000 l) lower in SSc patients than in healthy controls. In SSc patients, mean perfusion is reduced after CS (P < 0.0001) and skin flow recovery (significant difference between T(0) and T(4), P < 0.0001) is incomplete. In SSc patients with low vascular damage (early and active capillaroscopic groups), the abnormal microvascular response to CS involves only the digits, while the perfusion of hands dorsum is normal. With the progression of vascular damage (late capillaroscopic groups), the abnormal microvascular response to CS also appears in the hand dorsum skin. In PRP patients, baseline hand perfusion is very low and the skin flow recovery after CS is absent (P < 0.05). In early SSc, the thermoregulation of finger skin is impaired, but only in advanced stages of microangiopathy does the skin of the hand dorsum show a vasomotor control failure.

Zinc for organ pipe building.

Zinc is being used only rarely for organ pipes, since high quality material has not been available. The slightly harder metal makes manual processing of the pipes more complicated for the voicer. Nevertheless zinc is much more cost‐efficient. Grillo Werke (Germany) has developed a “soft zinc strip” which is significantly better, as far as workability is concerned, than materials available in the past. This material has been tested to determine to what extent zinc modifies pipe wall vibrations, and how essential the impact of the material would be on the sound. Various pairs of pipes made of plain metal and of zinc have been voiced for the same sound, if possible, according to subjective assessment. The experiments prove that the wall vibration spectra of flue pipes made of various materials clearly show differences. Total velocity spectra recorded by means of 3D scanning Doppler laser vibrometry vary considerably. The results of analyzing the stationary sound spectra and the attack transient, however, allow the voicing of these pipes to the same sound. Recording by a microphone array system also proved that the wall vibration does not have any direct influence on the sound radiation of the pipe.

Time course of acetylcholine‐induced activation of sympathetic efferents matches axon reflex sweating in humans

Action potentials from postganglionic C-fibres were recorded in healthy volunteers by microneurography in the peroneal nerve. Their responsiveness to mechanical or heat stimuli or to sympathetic reflex provocation tests was determined by transient slowing of conduction velocity following activation. Twenty units were classified as sympathetic efferent units. Acetylcholine (ACh) iontophoresis (10%, 1 mA, 1 min) inside their innervation territory activated 8 of 20 sympathetic fibres with a mean delay of 61 ± 12 s, peak response at 175 ± 38 s, and a duration of 240 ± 42 s, whereas iontophoresis of saline did not activate any of them. The time course of neuronal activation correlated with the axon reflex sweating measured by an evaporimeter in a separate session (delay 76 ± 9 s, peak at 195 ± 12 s, decline to 50% of peak 312 ± 25 s). No ACh-induced vasoconstriction was observed by laser Doppler scanning (n = 11) even after depletion of neuropeptides by chronic topical capsaicin treatment (n = 8). We conclude that ACh iontophoresis activates about half of the sympathetic fibres in human skin and provokes a corresponding axon reflex sweating. The absence of ACh-induced vasoconstriction even after the depletion of neuropeptides by capsaicin suggests that only sudomotor fibres, but not sympathetic vasoconstrictor fibres are activated by this stimulus.

Basal nitric oxide activity is an independent determinant of arteriolar structure in the human retinal circulation

Experimental data indicate that nitric oxide might play a role in structure and remodeling of peripheral small arteries and arterioles. We hypothesized that retinal arteriolar structure is modulated by basal nitric oxide activity. The study cohort comprised 97 male untreated patients with normal and elevated blood pressure but without clinical evidence for cardiovascular disease. The changes of retinal capillary blood flow (RCF) to nitric oxide synthase inhibitor N-monomethyl-L-arginine (L-NMMA), that reflects basal nitric oxide activity of retinal vasculature, and to flicker light, that in part nitric oxide dependently provokes retinal vasodilatation, and parameters of retinal arteriolar structure, for example wall-to-lumen ratio (WLR), were assessed noninvasively and in vivo by scanning laser Doppler flowmetry. Participants were stratified according to the median WLR of retinal arterioles into two groups. In the group with WLR above the median RCF in response to infusion of L-NMMA decreased to a smaller extent (-3.82 ± 26 vs. -26.0 ± 45 arbitrary units and -0.83 ± 8.4 vs. -5.88 ± 11%, P = 0.004 and P = 0.015; respectively), whereas RCF in response to flicker light did not differ significantly compared to the counter group (22.2 ± 56 vs. 39.8 ± 51 arbitrary units and 7.42 ± 15 vs. 11.9 ± 14%, P = 0.112 and P = 0.149). In the whole study cohort WLR of retinal arterioles was related with the decrease of RCF to L-NMMA infusion [when expressed in absolute terms (r = 0.252, P = 0.013) and in percentage change (r = 0.213, P = 0.036)] and inversely related with the change of RCF to flicker light [when expressed in absolute terms (r = -0.203, P = 0.048) but not clearly when expressed in percentage change (r = -0.161, P = 0.120)]. Adjustment for major cardiovascular risk factors and changes of systemic hemodynamics in response to L-NMMA infusion revealed an independent relationship between WLR of retinal arterioles and percentage change of RCF to L-NMMA infusion (ß = 0.300, P = 0.007). Basal nitric oxide activity emerged as an independent determinant of arteriolar remodeling in the human retinal circulation in vivo.

Liver-Assist Device With a Microfluidics-Based Vascular Bed in an Animal Model

This study evaluates a novel liver-assist device platform with a microfluidics-modeled vascular network in a femoral arteriovenous shunt in rats. Liver-assist devices in clinical trials that use pumps to force separated plasma through packed beds of parenchymal cells exhibited significant necrosis with a negative impact on function. Microelectromechanical systems technology was used to design and fabricate a liver-assist device with a vascular network that supports a hepatic parenchymal compartment through a nanoporous membrane. Sixteen devices with rat primary hepatocytes and 12 with human HepG2/C3A cells were tested in athymic rats in a femoral arteriovenous shunt model. Several parenchymal tube configurations were evaluated for pressure profile and cell survival. The blood flow pattern and perfusion status of the devices was examined by laser Doppler scanning. Cell viability and serum protein secretion functions were assessed. Femoral arteriovenous shunt was successfully established in all animals. Blood flow was homogeneous through the vascular bed and replicated native flow patterns. Survival of seeded liver cells was highly dependent on parenchymal chamber pressures. The tube configuration that generated the lowest pressure supported excellent cell survival and function. This device is the first to incorporate a microfluidics network in the systemic circulatory system. The microvascular network supported viability and function of liver cells in a short-term ex vivo model. Parenchymal chamber pressure generated in an arteriovenous shunt model is a critical parameter that affects viability and must be considered in future designs. The microfluidics-based vascular network is a promising platform for generating a large-scale medical device capable of augmenting liver function in a clinical setting.

Self-assembled nanoparticles of functional copolymers for photonic applications

A modified emulsion copolymerization of phenylacetylene (PA) with hydrophilic monomers having different functions, i.e., acrylic acid (AA) and N,N-dimethylpropargylamine (DMPA) respectively, yields functionalized polymeric P(PA-co-AA) and P(PA-co-DMPA) nanoparticles. The systematic investigation on the experimental parameters affecting size, surface charge and polydispersity of the copolymers (initiator concentration, reaction time, cosolvent and PA/comonomer ratios) allows to modulate the nanoparticle physico-chemical properties. Spherical shaped particles with diameters in the range 80–500 nm, low polydispersity (PI values in the range 1.11–1.30) and different surface charge densities, between 0.44 and 2.87 μC/cm 2, have been consistently obtained and characterized by means of Dynamic Light Scattering (DLS), laser Doppler electrophoretic and Scanning Electron Microscopy (SEM) studies. XPS measurements have provided information on the nanoparticles chemical surface structure and suggest that AA and DMPA units are preferentially distributed on the surface of the spheres. The nanospheres self-assemble giving large domains (9.5 × 14.5 μm). Photonic analysis of the self-assembled copolymeric nanoparticles has been performed by means of Spectroscopic Ellipsometry (SE) and Bragg reflection spectroscopy, both of them demonstrating a three-dimensional photonic crystal property of these systems.