Philipp Thurner
Research interests
-
InterestsNano Biomaterial
Publications
-
3.98Impact points
A new look at the pathogenesis of asthma.
Clinical science (London, England : 1979). 04/2010; 118(7):439-50.
Asthma is an inflammatory disorder of the conducting airways that has strong association with allergic sensitization. The disease is characterized by a polarized Th-2 (T-helper-2)-type T-cell response, but in general targeting this component of the disease with selective therapies has been disappoin... [more] Asthma is an inflammatory disorder of the conducting airways that has strong association with allergic sensitization. The disease is characterized by a polarized Th-2 (T-helper-2)-type T-cell response, but in general targeting this component of the disease with selective therapies has been disappointing and most therapy still relies on bronchodilators and corticosteroids rather than treating underlying disease mechanisms. With the disappointing outcomes of targeting individual Th-2 cytokines or manipulating T-cells, the time has come to re-evaluate the direction of research in this disease. A case is made that asthma has its origins in the airways themselves involving defective structural and functional behaviour of the epithelium in relation to environmental insults. Specifically, a defect in barrier function and an impaired innate immune response to viral infection may provide the substrate upon which allergic sensitization takes place. Once sensitized, the repeated allergen exposure will lead to disease persistence. These mechanisms could also be used to explain airway wall remodelling and the susceptibility of the asthmatic lung to exacerbations provoked by respiratory viruses, air pollution episodes and exposure to biologically active allergens. Variable activation of this epithelial-mesenchymal trophic unit could also lead to the emergence of different asthma phenotypes and a more targeted approach to the treatment of these. It also raises the possibility of developing treatments that increase the lung's resistance to the inhaled environment rather than concentrating all efforts on trying to suppress inflammation once it has become established.
-
4.09Impact points
Osteopontin deficiency increases bone fragility but preserves bone mass.
Bone. 02/2010; 46(6):1564-73.
The ability of bone to resist catastrophic failure is critically dependent upon the material properties of bone matrix, a composite of hydroxyapatite, collagen type I, and noncollagenous proteins. These properties include elastic modulus, hardness, and fracture toughness. Like other aspects of bone ... [more] The ability of bone to resist catastrophic failure is critically dependent upon the material properties of bone matrix, a composite of hydroxyapatite, collagen type I, and noncollagenous proteins. These properties include elastic modulus, hardness, and fracture toughness. Like other aspects of bone quality, matrix material properties are biologically-defined and can be disrupted in skeletal disease. While mineral and collagen have been investigated in greater detail, the contribution of noncollagenous proteins such as osteopontin to bone matrix material properties remains unclear. Several roles have been ascribed to osteopontin in bone, many of which have the potential to impact material properties. To elucidate the role of osteopontin in bone quality, we evaluated the structure, composition, and material properties of bone from osteopontin-deficient mice and wild-type littermates at several length scales. Most importantly, the results show that osteopontin deficiency causes a 30% decrease in fracture toughness, suggesting an important role for OPN in preventing crack propagation. This significant decline in fracture toughness is independent of changes in whole bone mass, structure, or matrix porosity. Using nanoindentation and quantitative backscattered electron imaging to evaluate osteopontin-deficient bone matrix at the micrometer level, we observed a significant reduction in elastic modulus and increased variability in calcium concentration. Matrix heterogeneity was also apparent at the ultrastructural level. In conclusion, we find that osteopontin is essential for the fracture toughness of bone, and reduced toughness in osteopontin-deficient bone may be related to the increased matrix heterogeneity observed at the micro-scale. By exploring the effects of osteopontin deficiency on bone matrix material properties, composition and organization, this study suggests that reduced fracture toughness is one mechanism by which loss of noncollagenous proteins contribute to bone fragility.
-
4.39Impact points
Effect of Ca2+ ions on the adhesion and mechanical properties of adsorbed layers of human Osteopontin.
Biophysical journal. 07/2008;
Using an Atomic Force Microscope (AFM) and a Surface Force Apparatus (SFA) we have measured the surface coverage, adhesion and mechanical properties of layers of Osteopontin (OPN), a phosphoprotein of the human bones, adsorbed on mica. OPN is believed to connect collagen fibrils of the bone in a mat... [more] Using an Atomic Force Microscope (AFM) and a Surface Force Apparatus (SFA) we have measured the surface coverage, adhesion and mechanical properties of layers of Osteopontin (OPN), a phosphoprotein of the human bones, adsorbed on mica. OPN is believed to connect collagen fibrils of the bone in a matrix that dissipates energy, reducing the risk of fractures. AFM normal force measurements showed large adhesion and energy dissipation upon retraction of the tip, which were due to the breaking of the many OPN-OPN and OPN-mica bonds formed during tip-sample contact. The dissipated energy increased in the presence of Ca(2+) ions due to the formation of additional OPN-OPN and OPN-mica salt bridges between negative charges. The forces measured by SFA between two macroscopic mica surfaces were mainly repulsive and became hysteretic only in the presence of Ca(2+): adsorbed layers underwent an irreversible compaction during compression due to the formation of long-lived calcium salt bridges. This provides an energy storage mechanism, which is complementary to energy dissipation and may be equally relevant to bone recovery after yield. The prevalence of one mechanism or the other appears to depend on the confinement geometry, adsorption protocol and loading-unloading rates.
-
9.99Impact points
Nanoscale ion mediated networks in bone: osteopontin can repeatedly dissipate large amounts of energy.
Nano letters. 09/2007; 7(8):2491-8.
In the nanocomposite bone, inorganic material is combined with several types of organic molecules, and these complexes have been proposed to increase the bone strength. Here we report on a mechanism of how one of these components, human osteopontin, forms large mechanical networks that can repeatedl... [more] In the nanocomposite bone, inorganic material is combined with several types of organic molecules, and these complexes have been proposed to increase the bone strength. Here we report on a mechanism of how one of these components, human osteopontin, forms large mechanical networks that can repeatedly dissipate energy through work against entropy by breaking sacrificial bonds and stretching hidden length. The behavior of these in vitro networks is similar to that of organic components in bone, acting as an adhesive layer in between mineralized fibrils.
-
3.04Impact points
Three-dimensional characterization of cell clusters using synchrotron-radiation-based micro-computed tomography.
Microscopy and microanalysis : the official journal of Microscopy Society of America, Microbeam Analysis Society, Microscopical Society of Canada. 05/2006; 12(2):97-105.
Micro-computed tomography with the highly intense, monochromatic X rays produced by the synchrotron is a superior method to nondestructively measure the local absorption in three-dimensional space. Because biological tissues and cells consist mainly of water as the surrounding medium, higher absorbi... [more] Micro-computed tomography with the highly intense, monochromatic X rays produced by the synchrotron is a superior method to nondestructively measure the local absorption in three-dimensional space. Because biological tissues and cells consist mainly of water as the surrounding medium, higher absorbing agents have to be incorporated into the structures of interest. Even without X-ray optics such as refractive lens, one can uncover the stain distribution with the spatial resolution of about 1 mum. Incorporating the stain at selected cell compartments, for example, binding to the RNA/DNA, their density distribution becomes quantified. In this communication, we demonstrate that tomograms obtained at the beamlines BW2 and W2 (HASYLAB at DESY, Hamburg, Germany) and 4S (SLS, Villigen, Switzerland) clearly show that the RNA/DNA-stained HEK 293 cell clusters have a core of high density and a peripheral part of lower density, which correlate with results of optical microscopy. The inner part of the clusters is associated with nonvital cells as the result of insufficient oxygen and nutrition supply. This necrotic part is surrounded by (6 +/- 1) layers of vital cells.
-
4.39Impact points
Sacrificial bonds and hidden length: unraveling molecular mesostructures in tough materials.
Biophysical journal. 03/2006; 90(4):1411-8.
Sacrificial bonds and hidden length in structural molecules and composites have been found to greatly increase the fracture toughness of biomaterials by providing a reversible, molecular-scale energy-dissipation mechanism. This mechanism relies on the energy, of order 100 eV, needed to reduce entrop... [more] Sacrificial bonds and hidden length in structural molecules and composites have been found to greatly increase the fracture toughness of biomaterials by providing a reversible, molecular-scale energy-dissipation mechanism. This mechanism relies on the energy, of order 100 eV, needed to reduce entropy and increase enthalpy as molecular segments are stretched after being released by the breaking of weak bonds, called sacrificial bonds. This energy is relatively large compared to the energy needed to break the polymer backbone, of order a few eV. In many biological cases, the breaking of sacrificial bonds has been found to be reversible, thereby additionally providing a "self-healing" property to the material. Due to the nanoscopic nature of this mechanism, single molecule force spectroscopy using an atomic force microscope has been a useful tool to investigate this mechanism. Especially when investigating natural molecular constructs, force versus distance curves quickly become very complicated. In this work we propose various types of sacrificial bonds, their combination, and how they appear in single molecule force spectroscopy measurements. We find that by close analysis of the force spectroscopy curves, additional information can be obtained about the molecules and their bonds to the native constructs.
-
3.17Impact points
Non-destructive three-dimensional evaluation of a polymer sponge by micro-tomography using synchrotron radiation.
Biomolecular engineering. 09/2002; 19(2-6):73-8.
X-ray micro-tomography, a non-destructive technique is used to uncover the complex 3-D micro-architecture of a degradable polymer sponge designed for bone augmentation. The measurements performed at HASYLAB at DESY are based on a synchrotron radiation source resulting in a spatial resolution of abou... [more] X-ray micro-tomography, a non-destructive technique is used to uncover the complex 3-D micro-architecture of a degradable polymer sponge designed for bone augmentation. The measurements performed at HASYLAB at DESY are based on a synchrotron radiation source resulting in a spatial resolution of about 5.4 microm. In the present communication we report the quantitative analysis of the porosity and of the pore architecture. First, we elucidate that synchrotron radiation at the photon energy of 9 keV has an appropriate cross section for this low-weight material. Modifications in sponge micro-architecture during measurement are not detected. Second, the treatment of the data, an amount of 2.5 Gbyte to generate binary data is described. We compare the 3-D with the 2-D analysis in a quantitative manner. The obtained values for the mean distance to material within the sponge calculated from 2-D and 3-D data of the whole tomogram differ significantly: 12.5 microm for 3-D and 17.6 microm for 2-D analysis. If the pores exhibit a spherical shape as frequently found, the derived mean pore diameter, however, is overestimated only by 6% in the 2-D image analysis with respect to the 3-D evaluation. This approach can be applied to different porous biomaterials and composites even in a hydrated state close to physiological conditions, where any surface preparation artifact is avoided.
-
Imaging of cellular and extra-cellular stressed matter using synchrotron radiation based micro-computed tomography [microform] /
Thesis (doctoral)--Swiss Federal Institute of Technology Zurich, 2004.
-
2.07Impact points
Components for high speed atomic force microscopy.
Ultramicroscopy. 106(8-9):881-7.
Many applications in materials science, life science and process control would benefit from atomic force microscopes (AFM) with higher scan speeds. To achieve this, the performance of many of the AFM components has to be increased. In this work, we focus on the cantilever sensor, the scanning unit a... [more] Many applications in materials science, life science and process control would benefit from atomic force microscopes (AFM) with higher scan speeds. To achieve this, the performance of many of the AFM components has to be increased. In this work, we focus on the cantilever sensor, the scanning unit and the data acquisition. We manufactured 10 microm wide cantilevers which combine high resonance frequencies with low spring constants (160-360 kHz with spring constants of 1-5 pN/nm). For the scanning unit, we developed a new scanner principle, based on stack piezos, which allows the construction of a scanner with 15 microm scan range while retaining high resonance frequencies (>10 kHz). To drive the AFM at high scan speeds and record the height and error signal, we implemented a fast Data Acquisition (DAQ) system based on a commercial DAQ card and a LabView user interface capable of recording 30 frames per second at 150 x 150 pixels.
-
Blood vessel staining in the myocardium for 3D visualization down to the smallest capillaries
Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms.
Blood vessels formed after medical interventions such as radiofrequency treatment have to be visualized down to the capillary level with diameters of about 5 μm to validate neo-vascularization. Synchrotron radiation-based micro-computed tomography (SRμCT) provides the necessary spatial resolution. S... [more] Blood vessels formed after medical interventions such as radiofrequency treatment have to be visualized down to the capillary level with diameters of about 5 μm to validate neo-vascularization. Synchrotron radiation-based micro-computed tomography (SRμCT) provides the necessary spatial resolution. Since both the vessels and the surrounding tissue mainly consist of water the difference in absorption is extremely weak. Therefore, it is necessary to search for appropriate contrast agents and to develop suitable staining protocols, which finally allow segmenting the vessel tree. Among the contrast agents used in medicine lyophilic salts with a mean particle diameter of 1.5 μm such as CaSO4, SrSO4 and BaSO4 are most appropriate to stain the vessels. The combination of these salts with a commercially available embedding kit (JB-4, Polysciences Inc.) allows tissue fixation and long-term storage in solid state. Intensity-based segmentation algorithms enable the vessel tree extraction in selected parts of the stained myocardium using the SRμCT data.
-
Design and input-shaping control of a novel scanner for high-speed atomic force microscopy
Mechatronics.
A novel design of a scanning unit for atomic force microscopy (AFM) is presented that enables scanning speeds three orders of magnitude faster than compared to conventional AFMs. The new scanner is designed for high mechanical resonance frequencies, based on a new scanner design, which is optimized ... [more] A novel design of a scanning unit for atomic force microscopy (AFM) is presented that enables scanning speeds three orders of magnitude faster than compared to conventional AFMs. The new scanner is designed for high mechanical resonance frequencies, based on a new scanner design, which is optimized using finite element analysis. For high-speed scanning a new controller, based on input-shaping techniques, has been developed that reduces imaging artifacts due to the scanner’s dynamics. The implementation of the new AFM system offers imaging capabilities of several thousand lines per second with a scanning range of 13 μm in both scanning directions, and the freedom to choose the fast scan-axis in any arbitrary direction in the X–Y-plane.
-
Hierarchical interconnections in the nano-composite material bone: Fibrillar cross-links resist fracture on several length scales
Composites Science and Technology.
Bone is a complex and very important multi-constituent bio-composite. In this work, we focus on the arrangement of bone constituents from the nanoscopic to the microscopic scale, and investigate the influence of their arrangements on the fracture mechanisms of the whole composite. We find that bone,... [more] Bone is a complex and very important multi-constituent bio-composite. In this work, we focus on the arrangement of bone constituents from the nanoscopic to the microscopic scale, and investigate the influence of their arrangements on the fracture mechanisms of the whole composite. We find that bone, on the nanoscopic scale, consists of mineralized collagen fibrils held together by a non-fibrillar organic matrix, which results in a primary failure mode of delamination between mineralized fibrils. In turn, these mineralized fibrils form one of three types of filaments that span microcracks in fractured bone samples, possibly resisting the propagation of these cracks.
-
The effect of NaF in vitro on the mechanical and material properties of trabecular and cortical bone
High doses of sodium fluoride in bones lead to severe softening, by weakening interfacial properties between the inorg. minerals and the org. components, while leaving mineralization unchanged. This leads to redn. of microdamage and assocd. stress-whitening pointing to a change in failure mode. Acco... [more] High doses of sodium fluoride in bones lead to severe softening, by weakening interfacial properties between the inorg. minerals and the org. components, while leaving mineralization unchanged. This leads to redn. of microdamage and assocd. stress-whitening pointing to a change in failure mode. Accordingly, elastic modulus, failure stress, and indentation-distance increase are decreased, whereas failure strain is increased. [on SciFinder (R)]
-
Atomic force microscopy and indentation force measurement of bone.
Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology. 1(6):624-49.
This review is summarizing the results obtained from atomic force microscopy (AFM) and nanoindentation experiments to date. The combination of both techniques is especially powerful. It allows to carefully choose indentation locations as well as the post-hoc analysis of the created indents, and henc... [more] This review is summarizing the results obtained from atomic force microscopy (AFM) and nanoindentation experiments to date. The combination of both techniques is especially powerful. It allows to carefully choose indentation locations as well as the post-hoc analysis of the created indents, and hence the possibility to assess the properties of microstructural elements of bonessue. In addition, AFM has improved our understanding of bone ultrastructure and force spectroscopy experiments have led to the discovery of a molecular self-healing effect of bone that may be based on a small fraction of unstructured proteins. Nanoindentation measurements on bone, pose inherent problems since bone is an anisotropic solid showing elastic, viscoelastic, and time-dependent plastic behavior. Hence, derived parameters such as elastic modulus and hardness are to some extent dependent on measurement protocols. However, the development of extensions to the Oliver-Pharr method, being the most widely used analysis method, as well as novel dynamic testing techniques could improve the situation. Nanoindentation is widely used to study bone tissue and some important principal findings have been reported to date. These are presented here together with specific results from nanoindentation experiments of human and animal bones and tables are presented collating the data that can be found in the literature to date.
Following (1)
-
Dieter Pahr
Technische Universität Wien
