The ability of the atomic force microscope to measure forces with subnanonewton sensitivity at nanometer-scale lateral resolutions has led to its use in the mechanical characterization of nanomaterials. Recent studies have shown that the atomic force microscope can be used to measure the elastic moduli of suspended fibers by performing a nanoscale three-point bending test, in which the center of the fiber is deflected by a known force. We extend this technique by modeling the deflection measured at several points along a suspended fiber, allowing us to obtain more accurate data, as well as to justify the mechanical model used. As a demonstration, we have measured a value of 78 +/- 17 GPa for Young's modulus of bacterial cellulose fibers with diameters ranging from 35 to 90 nm. This value is considerably higher than previous estimates, obtained by less direct means, of the mechanical strength of individual cellulose fibers.
Compliance mismatch between the synthetic graft and the surrounding native tissue has been reported as a major factor in ultimate failure of the currently used cardiovascular graft replacements. Thus, developing biomaterials that display close mechanical properties as the tissue it is replacing is an important objective in biomedical devices design. Polyvinyl alcohol (PVA) is a biocompatible hydrogel with characteristics desired for biomedical applications. It can be crosslinked by a low temperature thermal cycling process. By using a novel thermal processing method under an applied strain and with the addition of a small amount of bacterial cellulose (BC) nanofibers, an anisotropic PVA-BC nanocomposite was created. The stress-strain tensile properties of porcine aorta were closely matched in both the circumferential and the axial directions by one type of anisotropic PVA-BC nanocomposite (10% PVA with 0.3% BC at 75% initial strain and cycle 2) within physiological range, with improved resistance to further stretch beyond physiological strains. The PVA-BC nanocomposite gives a broad range of mechanical properties, including anisotropy, by controlling material and processing parameters. PVA-BC nanocomposites with controlled degree of anisotropy that closely match the mechanical properties of the soft tissue it might replace, ranging from cardiovascular to other connective tissues, can be created.
Carbon nanotubes (CNTs) are widely hailed as the strongest material known to mankind. However, experimental measurements—and even theoretical estimates—of their mechanical properties span a wide range. We present an atomic force microscopy study of multiwalled CNTs, which, unlike previous such studies, measures the tube compliance as a function of position along suspended tubes. This permits a simultaneous determination of the effective Young’s and shear moduli of CNTs: 350±110 and 1.4±0.3GPa, respectively.
Background We have developed a blood‐brain barrier (BBB) crossing anti‐amyloid fusion protein KG207 as a potential AD therapeutic. This humanized bi‐functional molecule was generated by fusing an Aß oligomer (AßO)‐ binding peptide (ABP) with a BBB carrier FC5 via IgG‐1 Fc fragment. Present study shows that KG207 crosses the BBB in vitro and in vivo (mouse, rat and dog), penetrates target regions of the brain (cortex and hippocampus) and engages parenchymal Aß. KG207 neutralizes AßO‐induced toxicity in vitro and does not stimulate pro‐inflammatory cytokine production in mouse microglia. Studies demonstrated that KG207 was safe up to 300 mg/kg. Method Recombinant KG207 was produced in CHO cells. BBB‐permeability was assessed using in vitro BBB (formed by rat or human brain endothelial cells) and in vivo (rat, mouse and dog) models. AßO binding was determined by ELISA. Following iv injection, serum, CSF and brain levels of KG207 and Aß were assessed by nanoLC‐ MRM, ELISA and Western blot methods. Aß toxicity studies were done in human neuroblastoma (SH‐SY5Y) cells and rat primary cortical neuronal cells. Following exposure to KG207, cytokine levels in BV2 microglia were measured using Millipore Luminex assay kit. Safety studies were done in Sprague Dawley rats at 30, 100 and 300 mg/kg. Result KG207 retained both Aß‐oligomer binding activity and BBB‐permeability in vitro. When injected iv into rats and mouse, KG207 rapidly appeared in the CSF and brain parenchyma (cortex and hippocampus) indicating active transport of ABP across BBB by FC5 in vivo. In AD transgenic mice, KG207 treatment showed a significant reduction of brain Aß levels. KG207 significantly reduced AßO‐induced toxicity in both human neuroblastoma cells and primary cortical neurons in vitro. KG207 blocked AßO binding to cellular proteins in vitro. KG207 did not activate BV2 mouse microglia and induce pro‐inflammatory cytokines. No adverse effects were seen in rats injected with up to 300 mg/kg, including neurotoxicity. Conclusion Collectively, these results indicate that KG207 can effectivey cross the blood‐brain barrier, penetrate the brain and facilitate Aß clearance in vivo. In vitro data suggest that KG207 can safely clear Aß without eliciting pro‐inflammatory cytokine secretion by microglia.
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