Effects of mineralization on the hierarchical organization of collagen-a synchrotron X-ray scattering and polarized second harmonic generation study.

The process of mineralization fundamentally alters collagenous tissue biomechanics. While the structure and organization of mineral particles have been widely studied, the impact of mineralization on collagen matrix structure, particularly at the molecular scale, requires further investigation. In this study, synchrotron X-ray scattering (XRD) and polarization-resolved second harmonic generation microscopy (pSHG) were used to study normally mineralizing turkey leg tendon in tissue zones representing different stages of mineralization.

Interaction of Epsilon Toxin with the Plasma Membrane: The Role of Amino Acids Y42, Y43 and H162.

epsilon toxin (Etx) is a pore forming toxin that causes enterotoxaemia in ruminants and may be a cause of multiple sclerosis in humans. To date, most in vitro studies of Etx have used the Madin-Darby canine kidney (MDCK) cell line. However, studies using Chinese hamster ovary (CHO) cells engineered to express the putative Etx receptor, myelin and lymphocyte protein (MAL), suggest that amino acids important for Etx activity differ between species.

The biomechanics of metaphyseal cone augmentation in revision knee replacement.

The demand for revision knee replacement (RKR) has increased dramatically with rising patient life expectancy and younger recipients for primary TKR. However, significant challenges to RKR arise from osseous defects, reduced bone quality, potential bone volume loss from implant removal and the need to achieve implant stability. This study utilizes the outcomes of an ongoing RKR clinical trial using porous metaphyseal cones 3D-printed of titanium, to investigate 1) bone mineral density (BMD) changes in three fixation zones (epiphysis, metaphysis, and diaphysis) over a year and 2) the biomechanical effects of the cones at 6 months post-surgery.

Microstructural Characterization of Resistance Artery Remodelling in Diabetes Mellitus.

Introduction: Microvascular remodelling is a symptom of cardiovascular disease. Despite the mechanical environment being recognized as a major contributor to the remodelling process, it is currently only understood in a rudimentary way.

Objective: A morphological and mechanical evaluation of the resistance vasculature in health and diabetes mellitus.

Matrix-Bound Growth Factors are Released upon Cartilage Compression by an Aggrecan-Dependent Sodium Flux that is Lost in Osteoarthritis.

Unlabelled: Articular cartilage is a dense extracellular matrix-rich tissue that degrades following chronic mechanical stress, resulting in osteoarthritis (OA). The tissue has low intrinsic repair especially in aged and osteoarthritic joints. Here, we describe three pro-regenerative factors; fibroblast growth factor 2 (FGF2), connective tissue growth factor, bound to transforming growth factor-beta (CTGF-TGFβ), and hepatoma-derived growth factor (HDGF), that are rapidly released from the pericellular matrix (PCM) of articular cartilage upon mechanical injury.

Multiphoton imaging and Raman spectroscopy of the bovine vertebral endplate.

The interface between the intervertebral disc and the vertebral body is important to the discs' biomechanics and physiology, and is widely implicated in its pathology. This study aimed to explore biochemically and structurally the bony endplate, cartilage endplate and intervertebral disc, below the nucleus and below the annulus in healthy bovine tails. Multiphoton imaging and spontaneous Raman spectroscopy were employed.

Intermittent compression induces transitory hypoxic stimuli, upstream vasodilation and enhanced perfusion of skin capillaries, independent of age and diabetes.

The benefit of enhanced shear stress to the vascular endothelium has been well-documented in conduit arteries but is less understood in skin microcirculation. The aim of this study was to provide physiological evidence of the vascular changes in skin microcirculation induced by intermittent pneumatic compression (IPC) of 1 s cuff inflation (130 mmHg) every 20 s to the palm of the hand for 30 min. The oxygenation and hemodynamics of dorsal mid-phalangeal finger skin microcirculation were assessed by laser Doppler fluximetry and reflectance spectroscopy before, during, and after IPC in 15 young (18-39 years old) and 39 older (40-80 years old) controls and 32 older subjects with type 2 diabetes mellitus.

Biosensors and Diagnostics for Fungal Detection.

Early detection is critical to the successful treatment of life-threatening infections caused by fungal pathogens, as late diagnosis of systemic infection almost always equates with a poor prognosis. The field of fungal diagnostics has some tests that are relatively simple, rapid to perform and are potentially suitable at the point of care. However, there are also more complex high-technology methodologies that offer new opportunities regarding the scale and precision of fungal diagnosis, but may be more limited in their portability and affordability.

Viscoelastic properties of biopolymer hydrogels determined by Brillouin spectroscopy: A probe of tissue micromechanics.

Many problems in mechanobiology urgently require characterization of the micromechanical properties of cells and tissues. Brillouin light scattering has been proposed as an emerging optical elastography technique to meet this need. However, the information contained in the Brillouin spectrum is still a matter of debate because of fundamental problems in understanding the role of water in biomechanics and in relating the Brillouin data to low-frequency macroscopic mechanical parameters.

An MRI study of solute transport in the intervertebral disc.

Objective: Quantitative magnetic resonance imaging was used to determine partition coefficients and characteristic time constants for diffusion of MRI contrast agents in disc tissue.

Materials And Methods: Twenty-two excised equine intervertebral discs were exposed to a range of contrast agents: six to manganese chloride, eight to Magnevist (gadopentetate dimeglumine) and eight to Gadovist (gadobutrol), and uptake into the disc was quantified in T-weighted images.

Results: Diffusion for all contrast agents was approximately 25% faster in the nucleus than in the outer annulus; disc-average time constants ranged from (2.

Investigation of changes in bone density and chemical composition associated with bone marrow oedema-type appearances in magnetic resonance images of the equine forelimb.

Background: The aetiology of bone marrow oedema-like abnormalities (BMOA) seen on magnetic resonance imaging (MRI) is as yet not fully understood. The current study aimed to investigate the potential of projection radiography and Raman microspectroscopy to provide information regarding the underlying physiological changes associated with BMOA in equine bone samples.

Methods: MRI was used to assess 65 limbs from 43 horses.

Collagen reorganization in cartilage under strain probed by polarization sensitive second harmonic generation microscopy.

Type II collagen fibril diameters in cartilage are beneath the diffraction limit of optical microscopy, which makes the assessment of collagen organization very challenging. In this work we use polarization sensitive second harmonic generation (P-SHG) imaging to map collagen organization in articular cartilage, addressing in particular its behaviour under strain and changes which occur in osteoarthritis. P-SHG yields two parameters, molecular order and orientation, which provide measures of the degree of organization both at the molecular scale (below the diffraction limit) and above a few hundred nanometres (at the image pixel size).

Interactions Between Immunotoxins and the Plasma Membrane: Implications for CAT-8015 Immunotoxin Therapy.

Acute Lymphoblastic Leukemia (ALL) remains the most frequent cause of cancer-related mortality in children and novel therapies are needed for the treatment of relapsed/refractory childhood ALL. One approach is the targeting of ALL blasts with the immunotoxin CAT-8015. Although CAT-8015 has potent anti-leukemia activity, with a 32% objective response rate in a phase 1 study of childhood ALL, haemolytic-uremic syndrome (HUS) and vascular leak syndrome (VLS), major dose-limiting toxicities, have limited the use of this therapeutic approach in children.

Novel hemodynamic structures in the human glomerulus.

To investigate human glomerular structure under conditions of physiological perfusion, we have analyzed fresh and perfusion-fixed normal human glomeruli at physiological hydrostatic and oncotic pressures using serial resin section reconstruction, confocal, multiphoton, and electron microscope imaging. Afferent and efferent arterioles (21.5 ± 1.

Structure of the Pacinian Corpuscle: Insights Provided by Improved Mechanical Modeling.

An improved model of the Pacinian corpuscle includes corrections for lamellar curvature. Results suggest that outer-zone lamellae produce a focusing effect whereby stimuli are channeled radially inwards. The requirements for this effect (large outer-surface area and thin, closely spaced lamellae) provide a rationale for the complexity of the outer-zone structure.

The effects of needle damage on annulus fibrosus micromechanics.

Unlabelled: Needle puncture of the intervertebral disc can initiate a mechanical and biochemical cascade leading to disc degeneration. Puncture's mechanical effects have been shown near the puncture site, mechanical effects should be observed far, relative to needle size, from the puncture site, given the disc-wide damage induced by the stab. The aim of this work was to quantify these far-field effects, and to observe the local structural damage provoked by the needle.

Lipid distribution, composition and uptake in bovine articular cartilage studied using Raman micro-spectrometry and confocal microscopy.

The distribution and composition of endogenous lipids in articular cartilage and transport of exogenous fatty acids have been investigated on a microscopic scale in fresh bovine articular cartilage. To investigate the distribution and composition of the endogenous lipids, hyperspectral Raman maps were taken of chondrocytes and their surrounding matrix in both the deep and superficial zones. These revealed differences in both lipid distribution and composition between the two zones.

Bovine and degenerated human annulus fibrosus: a microstructural and micromechanical comparison.

The complex structure of the annulus fibrosus is strongly related to its mechanical properties. Recent work showed that it is possible to observe the relative movement of fibre bundles in loaded cow tail annulus; the aim of this work was to describe and quantify annulus fibrosus micromechanics in degenerated human disc, and compare it with cow tail annulus, an animal model often used in the literature. Second harmonic generation was used to image the collagen matrix in twenty strips of annulus fibrosus harvested from intervertebral disc of seven patients undergoing surgery.

Magnetically controlled ferromagnetic swimmers.

Microscopic swimming devices hold promise for radically new applications in lab-on-a-chip and microfluidic technology, diagnostics and drug delivery etc. In this paper, we demonstrate the experimental verification of a new class of autonomous ferromagnetic swimming devices, actuated and controlled solely by an oscillating magnetic field. These devices are based on a pair of interacting ferromagnetic particles of different size and different anisotropic properties joined by an elastic link and actuated by an external time-dependent magnetic field.

Decrease in articular hypoxia and synovial blood flow at early time points following infliximab and etanercept treatment in rheumatoid arthritis.

Objectives: An important feature of rheumatoid arthritis (RA) is hypoxia-driven synovial angiogenesis, but the relationship between change in vascularity, as measured by power Doppler ultrasound (PDUS), and oxygen tensions is unaddressed.

Methods: Metacarpophalangeal (MCP) joint PDUS was assessed in 23 patients with RA, alongside arthroscopic synovitis and oxygen tension measurements, at baseline and 4 weeks after anti-tumour necrosis factor (TNF) inhibitors.

Results: Anti-TNF reduced PDUS scores, which were negatively correlated with rise in oxygen tensions.

Coacervation of α-elastin studied by ultrafast nonlinear infrared spectroscopy.

Elastin is the main protein to confer elasticity to biological tissues, through the formation of a hierarchical network of fibres. α-Elastin, a soluble form of the protein, is widely used in studies of the biosynthesis of human elastic tissue and exhibits coacervation in solution. This process involves the association of α-elastin molecules through a liquid-liquid phase transition, which is reversible unless the temperature is driven sufficiently high to induce the formation of insoluble aggregates.

Preparation of Extracellular Matrix Protein Fibers for Brillouin Spectroscopy.

Brillouin spectroscopy is an emerging technique in the biomedical field. It probes the mechanical properties of a sample through the interaction of visible light with thermally induced acoustic waves or phonons propagating at a speed of a few km/sec. Information on the elasticity and structure of the material is obtained in a nondestructive contactless manner, hence opening the way to in vivo applications and potential diagnosis of pathology.

Lamellar and fibre bundle mechanics of the annulus fibrosus in bovine intervertebral disc.

Unlabelled: The intervertebral disc is a multicomposite structure, with an outer fibrous ring, the annulus fibrosus, retaining a gel-like core, the nucleus pulposus. The disc presents complex mechanical behaviour, and it is of high importance for spine biomechanics. Advances in multiscale modelling and disc repair raised a need for new quantitative data on the finest details of annulus fibrosus mechanics.

Red Blood Cell Susceptibility to Pneumolysin: CORRELATION WITH MEMBRANE BIOCHEMICAL AND PHYSICAL PROPERTIES.

This study investigated the effect of the biochemical and biophysical properties of the plasma membrane as well as membrane morphology on the susceptibility of human red blood cells to the cholesterol-dependent cytolysin pneumolysin, a key virulence factor of Streptococcus pneumoniae, using single cell studies. We show a correlation between the physical properties of the membrane (bending rigidity and surface and dipole electrostatic potentials) and the susceptibility of red blood cells to pneumolysin-induced hemolysis. We demonstrate that biochemical modifications of the membrane induced by oxidative stress, lipid scrambling, and artificial cell aging modulate the cell response to the toxin.