ORCID Profile
0000-0002-2275-6170
Current Organisation
University Medical Center Utrecht
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Composite and Hybrid Materials | Functional Materials | Plasma Physics; Fusion Plasmas; Electrical Discharges | Materials Engineering
Expanding Knowledge in Engineering | Expanding Knowledge in the Biological Sciences | Environmentally Sustainable Manufacturing not elsewhere classified |
Publisher: IOP Publishing
Date: 30-03-2005
DOI: 10.1088/0967-3334/26/2/012
Abstract: In trabecular bone, the interrelationships of electrical and dielectric properties with mechanical characteristics are poorly known. Information on these relations is crucial for evaluation of the diagnostic potential of impedance techniques. In this study, electrical and dielectric properties, i.e. permittivity, conductivity, phase angle, loss factor, specific impedance and dissipation factor of human trabecular bone s les (n=26, harvested from the distal femur and proximal tibia) were characterized in a wide frequency range (50 Hz-5 MHz). Mechanical properties, i.e. Young's modulus, ultimate strength, yield stress, yield strain and resilience of the s les (n=20) were determined by using destructive compressive testing. Subsequently, measurements of electrical and dielectric properties were repeated after mechanical testing. The measurements were also repeated for the control s les (n=6) that were not mechanically tested. Electrical, dielectric or mechanical properties showed no significant differences between the intact femoral and tibial s les. The electrical and dielectric parameters as well as the linear correlations between the dielectric and electrical parameters with mechanical parameters were strongly frequency dependent. At the frequency of 1.2 MHz, the relative permittivity showed the strongest linear correlations with the Young's modulus (r=0.71, p<0.01, n=20) and ultimate strength (r=0.73, p<0.01, n=20). Permittivity and dissipation factor showed statistically significant changes after mechanical testing. Our results suggest that the measurements of low frequency electrical and dielectric properties may provide information on the mechanical status of trabecular bone and, possibly, may even help to diagnose bone microdamage. In the future, these measurement techniques may be further developed for use during open surgery, such as bone grafting or total hip replacement surgery.
Publisher: Elsevier BV
Date: 09-2018
DOI: 10.1016/J.JBIOMECH.2018.06.012
Abstract: As articular cartilage is an avascular tissue, the transport of nutrients and cytokines through the tissue is essential for the health of cells, i.e. chondrocytes. Transport of specific contrast agents through cartilage has been investigated to elucidate cartilage quality. In laboratory, pre-clinical and clinical studies, imaging techniques such as magnetic imaging resonance (MRI), computed tomography (CT) and fluorescent microscopy have been widely employed to visualize and quantify solute transport in cartilage. Many parameters related to the physico-chemical properties of the solute, such as molecular weight, net charge and chemical structure, have a profound effect on the transport characteristics. Information on the interplay of the solute parameters with the imaging-dependent parameters (e.g. resolution, scan and acquisition time) could assist in selecting the most optimal imaging systems and data analysis tools in a specific experimental set up. Here, we provide a comprehensive review of various imaging systems to investigate solute transport properties in articular cartilage, by discussing their potentials and limitations. The presented information can serve as a guideline for applications in cartilage imaging and therapeutics delivery and to improve understanding of the set-up of solute transport experiments in articular cartilage.
Publisher: Elsevier BV
Date: 12-2019
DOI: 10.1016/J.ACTBIO.2019.09.014
Abstract: Tissue engineering and regenerative medicine are two therapeutic strategies to treat, and to potentially cure, diseases affecting cartilaginous tissues, such as osteoarthritis and cartilage defects. Insights into the processes occurring during regeneration are essential to steer and inform development of the envisaged regenerative strategy, however tools are needed for longitudinal and quantitative monitoring of cartilage matrix components. In this study, we introduce a contrast-enhanced computed tomography (CECT)-based method using a cationic iodinated contrast agent (CA4+) for longitudinal quantification of glycosaminoglycans (GAG) in cartilage-engineered constructs. CA4+ concentration and scanning protocols were first optimized to ensure no cytotoxicity and a facile procedure with minimal radiation dose. Chondrocyte and mesenchymal stem cell pellets, containing different GAG content were generated and exposed to CA4+. The CA4+ content in the pellets, as determined by micro computed tomography, was plotted against GAG content, as measured by 1,9-dimethylmethylene blue analysis, and showed a high linear correlation. The established equation was used for longitudinal measurements of GAG content over 28 days of pellet culture. Importantly, this method did not adversely affect cell viability or chondrogenesis. Additionally, the CA4+ distribution accurately matched safranin-O staining on histological sections. Hence, we show proof-of-concept for the application of CECT, utilizing a positively charged contrast agent, for longitudinal and quantitative imaging of GAG distribution in cartilage tissue-engineered constructs. STATEMENT OF SIGNIFICANCE: Tissue engineering and regenerative medicine are promising therapeutic strategies for different joint pathologies such as cartilage defects or osteoarthritis. Currently, in vitro assessment on the quality and composition of the engineered cartilage mainly relies on destructive methods. Therefore, there is a need for the development of techniques that allow for longitudinal and quantitative imaging and monitoring of cartilage-engineered constructs. This work harnesses the electrostatic interactions between the negatively-charged glycosaminoglycans (GAGs) and a positively-charged contrast agent for longitudinal and non-destructive quantification of GAGs, providing valuable insight on GAG development and distribution in cartilage engineered constructs. Such technique can advance the development of regenerative strategies, not only by allowing continuous monitoring but also by serving as a pre-implantation screening tool.
Publisher: IOP Publishing
Date: 03-2006
DOI: 10.1088/0031-9155/51/6/019
Abstract: New quantitative ultrasound (QUS) techniques involving ultrasound backscattering have been introduced for the assessment of bone quality. QUS parameters are affected by the transducer characteristics, e.g. frequency range, wave and pulse length. Although frequency-dependent backscattering has been studied extensively, understanding of the ultrasound scattering phenomenon in trabecular bone is still limited. In the present study, the relationships between QUS parameters and the microstructure of human trabecular bone were investigated experimentally and by using numerical simulations. Speed of sound (SOS), normalized broadband ultrasound attenuation (nBUA), average attenuation, integrated reflection coefficient (IRC) and broadband ultrasound backscatter (BUB) were measured for 26 human trabecular bone cylinders. Subsequently, a high-resolution microCT system was used to determine the microstructural parameters. Moreover, based on the s le-specific microCT data, a numerical model for ultrasound propagation was developed for the simulation of experimental measurements. Experimentally, significant relationships between the QUS parameters and microstructural parameters were demonstrated. The relationships were dependent on the frequency, and the strongest association (r = 0.88) between SOS and structural parameters was observed at a centre frequency of 5 MHz. nBUA, average attenuation, IRC and BUB showed somewhat lower linear correlations with the structural properties at a centre frequency of 5 MHz, as compared to those determined at lower frequencies. Multiple regression analyses revealed that the variation of acoustic parameters could best be explained by parameters reflecting the amount of mineralized tissue. A principal component analysis demonstrated that the strongest determinants of BUB and IRC were related to the trabecular structure. However, other structural characteristics contributed significantly to the prediction of the acoustic parameters as well. The two-dimensional numerical model introduced in the present study demonstrated good agreement with the experimental measurements. However, further studies with the simulation model are warranted to systematically investigate the relation between the structural parameters and ultrasound scattering.
Publisher: IOP Publishing
Date: 31-03-2005
DOI: 10.1088/0031-9155/50/8/001
Abstract: The ultrasound (US) backscattering method has been introduced as an alternative for the through-transmission measurement of sound attenuation and speed in diagnosis of osteoporosis. Both attenuation and backscattering depend strongly on the US frequency. In this study, 20 human trabecular bone s les were measured in transmission and pulse-echo geometry in vitro. The aim of the study was to find the most sensitive frequency range for the quantitative ultrasound (QUS) analyses. Normalized broadband US attenuation (nBUA), speed of sound (SOS), broadband US backscatter (BUB) and integrated reflection coefficient (IRC) were determined for each s le. The s les were spatially scanned with five pairs of US transducers covering a frequency range of 0.2-6.7 MHz. Furthermore, mechanical properties and density of the same s les were determined. At all frequencies, SOS, BUB and IRC showed statistically significant linear correlations with the mechanical properties or density of human trabecular bone (0.51 < r < 0.82, 0.54 < r < 0.81 and 0.70 < r < 0.85, respectively). In contrast to SOS, IRC and BUB, nBUA showed statistically significant correlations with mechanical parameters or density at the centre frequency of 1 MHz only. Our results suggest that frequencies up to 5 MHz can be useful in QUS analyses for the prediction of bone mechanical properties and density. Since the use of higher frequencies provides better axial and spatial resolution, improved structural analyses may be possible. While extensive attenuation of high frequencies in trabecular bone limits the clinically feasible frequency range, selection of optimal frequency range for in vivo QUS application should be carefully considered.
Publisher: Wiley
Date: 28-08-2020
DOI: 10.1002/JOR.24824
Publisher: Elsevier BV
Date: 10-2019
DOI: 10.1016/J.BONE.2019.07.001
Abstract: Since Galileo's days the effect of size on the anatomical characteristics of the structural elements of the body has been a subject of interest. However, the effects of scaling at tissue level have received little interest and virtually no data exist on the subject with respect to the osteochondral unit in the joint, despite this being one of the most lesion-prone and clinically relevant parts of the musculoskeletal system. Imaging techniques, including Fourier transform infrared imaging, polarized light microscopy and micro computed tomography, were combined to study the response to increasing body mass of the osteochondral unit. We analyzed the effect of scaling on structural characteristics of articular cartilage, subchondral plate and the supporting trabecular bone, across a wide range of mammals at microscopic level. We demonstrated that, while total cartilage thickness scales to body mass in a negative allometric fashion, thickness of different cartilage layers did not. Cartilage tissue layers were found to adapt to increasing loads principally in the deep zone with the superficial layers becoming relatively thinner. Subchondral plate thickness was found to have no correlation to body mass, nor did bone volume fraction. The underlying trabecular bone was found to have thicker trabeculae (r=0.75, p<0.001), as expected since this structure carries most loads and plays a role in force mitigation. The results of this study suggest that the osteochondral tissue structure has remained remarkably preserved across mammalian species during evolution, and that in particular, the trabecular bone carries the adaptation to the increasing body mass.
Publisher: IOP Publishing
Date: 02-10-2006
DOI: 10.1088/0031-9155/51/20/014
Abstract: Microstructural changes, such as reduction of trabecular thickness and number, are characteristic signs of osteoporosis leading to diminished bone strength. Electrical and dielectric parameters might provide diagnostically valuable information on trabecular bone microstructure not extractable from bone mineral density measurements. In this study, structural properties of human trabecular bone s les (n=26) harvested from the distal femur and proximal tibia were investigated using the computed microtomography (microCT) technique. Quantitative parameters, e.g. structural model index (SMI) or trabecular bone volume fraction (BV/TV), were calculated. In addition, the s les were examined electrically over a wide frequency range (50 Hz-5 MHz) using a two-electrode impedance spectroscopy set-up. Relative permittivity, loss factor, conductivity, phase angle, specific impedance and dissipation factor were determined. Significant linear correlations were obtained between the dissipation factor and BV/TV or SMI (|r| 0.70, p<0.01, n=26). Principal component analyses, conducted on electrical and structural parameters, revealed that the high frequency principal component of the dissipation factor was significantly related to SMI (r=0.72, p<0.01, n=26). The linear combination of high and low frequency relative permittivity predicted 73% of the variation in BV/TV. To conclude, electrical and dielectric parameters of trabecular bone, especially relative permittivity and dissipation factor, were significantly and specifically related to a trabecular microstructure as characterized with microCT. The data gathered in this study constitute a useful basis for theoretical and experimental work towards the development of impedance spectroscopy techniques for detection of bone quality in vitro or in special cases of open surgery.
Publisher: The Royal Society
Date: 06-04-2014
Abstract: Patient-specific biomechanical models including patient-specific finite-element (FE) models are considered potentially important tools for providing personalized healthcare to patients with musculoskeletal diseases. A multi-step procedure is often needed to generate a patient-specific FE model. As all involved steps are associated with certain levels of uncertainty, it is important to study how the uncertainties of in idual components propagate to final simulation results. In this study, we considered a specific case of this problem where the uncertainties of the involved steps were known and the aim was to determine the uncertainty of the predicted strain distribution. The effects of uncertainties of three important components of patient-specific models, including bone density, musculoskeletal loads and the parameters of the material mapping relationship on the predicted strain distributions, were studied. It was found that the number of uncertain components and the level of their uncertainty determine the uncertainty of simulation results. The ‘average’ uncertainty values were found to be relatively small even for high levels of uncertainty in the components of the model. The ‘maximum’ uncertainty values were, however, quite high and occurred in the areas of the scapula that are of the greatest clinical relevance. In addition, the uncertainty of the simulation result was found to be dependent on the type of movement analysed, with abduction movements presenting consistently lower uncertainty values than flexion movements.
Start Date: 06-2019
End Date: 12-2022
Amount: $470,000.00
Funder: Australian Research Council
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