3,381 research outputs found
Cardiac multi-scale investigation of the right and left ventricle ex vivo: a review
The heart is a complex multi-scale system composed of components integrated at the subcellular, cellular, tissue and organ levels. The myocytes, the contractile elements of the heart, form a complex three-dimensional (3D) network which enables propagation of the electrical signal that triggers the contraction to efficiently pump blood towards the whole body. Cardiovascular diseases (CVDs), a major cause of mortality in developed countries, often lead to cardiovascular remodeling affecting cardiac structure and function at all scales, from myocytes and their surrounding collagen matrix to the 3D organization of the whole heart. As yet, there is no consensus as to how the myocytes are arranged and packed within their connective tissue matrix, nor how best to image them at multiple scales. Cardiovascular imaging is routinely used to investigate cardiac structure and function as well as for the evaluation of cardiac remodeling in CVDs. For a complete understanding of the relationship between structural remodeling and cardiac dysfunction in CVDs, multi-scale imaging approaches are necessary to achieve a detailed description of ventricular architecture along with cardiac function. In this context, ventricular architecture has been extensively studied using a wide variety of imaging techniques: ultrasound (US), optical coherence tomography (OCT), microscopy (confocal, episcopic, light sheet, polarized light), magnetic resonance imaging (MRI), micro-computed tomography (micro-CT) and, more recently, synchrotron X-ray phase contrast imaging (SR X-PCI). Each of these techniques have their own set of strengths and weaknesses, relating to sample size, preparation, resolution, 2D/3D capabilities, use of contrast agents and possibility of performing together with in vivo studies. Therefore, the combination of different imaging techniques to investigate the same sample, thus taking advantage of the strengths of each method, could help us to extract the maximum information about ventricular architecture and function. In this review, we provide an overview of available and emerging cardiovascular imaging techniques for assessing myocardial architecture ex vivo and discuss their utility in being able to quantify cardiac remodeling, in CVDs, from myocyte to whole organ
A Composite Material-based Computational Model for Diaphragm Muscle Biomechanical Simulation
Lung cancer is the most common cause of cancer related death among both men and women. Radiation therapy is the most widely used treatment for this disease. Motion compensation for tumor movement is often clinically important and biomechanics-based motion models may provide the most robust method as they are based on the physics of motion. In this study, we aim to develop a patient specific biomechanical model that predicts the deformation field of the diaphragm muscle during respiration. The first part of the project involved developing an accurate and adaptable micro-to-macro mechanical approach for skeletal muscle tissue modelling for application in a FE solver. The next objective was to develop the FE-based mechanical model of the diaphragm muscle based on patient specific 4D-CT data. The model shows adaptability to pathologies and may have the potential to be incorporated into respiratory models for the aid in treatment and diagnosis of diseases
Non-destructive quantification of tissue scaffolds and augmentation implants using X-ray microtomography
A three dimensional (3D), interconnected, porous structure is essential for bone tissue engineering scaffolds and skeletal augmentation implants. Current methods of characterising these structures, however, are limited to average properties such as percentage porosity. More accurate quantitative properties, such as pore and interconnect size distributions, are required. Once measured, these parameters need to be correlated to tissue regeneration and integration criteria, including solute transport, blood vessel regeneration, bone ingrowth, and mechanical properties. Ideally, these techniques would work in vitro and in vivo, and hence allow evaluation of osteoconduction and osseointegration after implantation.
This thesis will focus on developing and applying algorithms for use with X-ray microtomography (micro-CT or μCT) which can non-destructively image internal structure at the micron scale. The technique will be demonstrated on two separate materials: bioactive glass scaffolds and titanium (Ti) augmentation devices.
Using the developed techniques, the structural and compositional evolutions of bioactive glass scaffolds in a simulated body fluid (SBF) flow environment were quantified using micro-CT scans taken at different dissolution stages. Results show that 70S30C bioactive scaffolds retain favourable 3D structures during a 28 d dissolution experiment, with a modal equivalent pore diameter of 682 μm staying unchanged, and a modal equivalent interconnect diameter decreasing from 252 μm to 209 μm.
The techniques were then applied to porous Ti augmentation scaffolds. These scaffolds, produced by selective laser melting have very different pore networks with graded randomness and unit size. They present new challenges when applying the developed micro-CT quantification techniques. Using a further adapted methodology, the interconnecting pore sizes, strut thickness, and surface roughness were measured. This demonstrated the robustness of the methodologies and their applicability to a range of tissue scaffolds and augmentation devices
Tunable Acellular Hyaluronic Acid Hydrogel Systems to Attenuate Left Ventricular Remodeling
Following myocardial infarction (MI), left ventricular (LV) remodeling initiates a series of maladaptive events that may induce heart failure (HF). The use of injectable biomaterials is an attractive approach to attenuate negative remodeling; however, optimal properties for these systems have not been identified. The general hypothesis is that the properties of injectable hydrogels control the magnitude and duration of stabilization in the weakened myocardium and the ability to attenuate LV remodeling. To test this hypothesis, three specific aims were developed.
Increased stress due to geometric alterations is thought to exacerbate LV remodeling, causing infarct expansion. Aim 1 utilized methacrylated hyaluronic acid (MeHA) hydrogels to demonstrate ex vivo that macromer modification and oxidation-reduction (redox) initiator concentrations influence the mechanical properties of hydrogel/myocardium composites and their distribution in tissue. Experimental data incorporation into a finite element model of the dilated LV validated previous in vivo geometric outcomes and generally demonstrated the largest stress reduction with higher mechanics and larger volumes.
Aims 2 and 3 evaluated the influence of temporal mechanical support on LV remodeling in an in vivo MI model. Hydroxyethyl methacrylate groups were coupled to HA to produce hydrolytically degradable hydrogels (HeMA-HA) polymerized via redox reactions. In Aim 2, hydrogel gelation, mechanics, and degradation properties were varied by altering HeMA modification to yield low and high HeMA-HA with similar gelation and initial mechanics but accelerated degradation kinetics compared to previously studied low and high MeHA. High HeMA-HA was more effective than low HeMA-HA treatment in limiting remodeling; however, high HeMA-HA only limited LV dilation for 2 weeks, while its high MeHA counterpart sustained support up to 8 weeks. In Aim 3, a hydrogel/microsphere composite system was evaluated as an alternative approach to enhance temporal support via collagen bulking through controlled macrophage responses. The composite treatment increased myocardial thickness and decreased chamber volumes compared to hydrogel alone.
This work demonstrates the significance of the magnitude and duration of mechanical support in attenuating LV remodeling and provides insight on optimal material properties for injectable biomaterials to develop better therapies to prevent HF
MODELLING AND IN VIVO MONITORING OF THE TIME DEPENDENT MECHANICAL PROPERTIES OF TISSUE ENGINEERING SCAFFOLDS
When organs and tissue fail either due to pre-existing disease progression or by accidental damage, current state of the art treatment involves the replacement of the damaged or diseased tissue with new donor derived organs/tissue. The limitations of these current approaches include a limited supply of tissue for treatments and the immune response of the patient’s own body against the new implanted tissue/organs. To solve these issues, tissue engineering aims to develop artificial analogs derived from a patient’s own cells instead of donor tissue/organs for treatment. To this end, a promising approach, known as scaffold-based tissue engineering, is to seed engineered constructs or scaffolds with cells to form artificial analogs, which then develop with time into new tissue/organs for implantation. The mechanical properties of the scaffold play a critical role in the success of scaffold-based treatments, as the scaffold is expected to provide a temporary support for the generation of new tissue/organs without causing failure at any time during the treatment process. It is noted that due to the degradation of scaffold in the treatment process, the mechanical properties of the scaffold are not constant but change with time dynamically. This raises two scientific issues; one is the representation of the time-dependent mechanical properties and the other one is the monitoring of these properties, especially in the in vivo environments (i.e., upon the implantation of scaffolds into animal/patient bodies). To address these issues, this research is aimed at performing a novel study on the modelling and in vivo monitoring of the time dependent mechanical properties of tissue engineering scaffolds.
To represent the time-dependent mechanical properties of a scaffold, a novel model based on the concept of finite element model updating is developed. The model development involves three steps: (1) development of a finite element model for the effective mechanical properties of the scaffold, (2) parametrizing the finite element model by selecting parameters associated with the scaffold microstructure and/or material properties, which vary with scaffold degradation, and (3) identifying selected parameters as functions of time based on measurements from the tests on the scaffold mechanical properties as they degrade. To validate the developed model, scaffolds were
made from the biocompatible polymer polycaprolactone (PCL) mixed with hydroxyapatite (HA) nanoparticles and their mechanical properties were examined in terms of the Young modulus. Based on the bulk degradation exhibited by the PCL/HA scaffold, the molecular weight was selected for model updating. With the identified molecular weight, the finite element model
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developed was effective for predicting the time-dependent mechanical properties of PCL/HA scaffolds during degradation
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To monitor and characterize scaffold mechanical properties in vivo, novel methods based on synchrotron-based phase contrast imaging and finite element modeling were developed. The first method is to represent the scaffold mechanical properties from the measured deflection. In this method, the phase contrast imaging is used to characterize the scaffold deflection caused by ultrasound radiation forces; and the finite element modelling is used to represent the ultrasonic loading on the scaffold, thus predicting the mechanical properties from the measured deflection. The second method is to characterize the scaffold degradation due to surface erosion, which involves the remote sensing of the time dependent morphology of tissue scaffolds by phase contrast imaging and the estimation of time dependent mass loss of the scaffolds from the sensed morphology. The last method is to relate the elastic mechanical property and nonlinear stress-strain behavior to the scaffold geometry, both changing with time during surface erosion. To validate the above methods, scaffolds was made from varying biomaterials (PLGA and PCL) and their mechanical properties (degradation, mass loss, and elastic modulus) were examined experimentally. The results obtained illustrate the methods developed in this research are effective to monitor and characterize scaffold mechanical properties.
The significance of this research is that the model developed for the scaffold mechanical properties can be used in the design of scaffolds with the desired mechanical properties, instead of the trial and error methods typical in current scaffold design; and that these novel monitoring methods based on synchrotron imaging can be used to characterize the scaffold time-dependent mechanical properties in the in vivo environments, representing an important advance in tissue engineering
Overcoming conventional modeling limitations using image- driven lattice-boltzmann method simulations for biophysical applications
The challenges involved in modeling biological systems are significant and push the boundaries of conventional modeling. This is because biological systems are distinctly complex, and their emergent properties are results of the interplay of numerous components/processes. Unfortunately, conventional modeling approaches are often limited by their inability to capture all these complexities. By using in vivo data derived from biomedical imaging, image-based modeling is able to overcome this limitation.
In this work, a combination of imaging data with the Lattice-Boltzmann Method for computational fluid dynamics (CFD) is applied to tissue engineering and thrombogenesis. Using this approach, some of the unanswered questions in both application areas are resolved.
In the first application, numerical differences between two types of boundary conditions: “wall boundary condition” (WBC) and “periodic boundary condition” (PBC), which are commonly utilized for approximating shear stresses in tissue engineering scaffold simulations is investigated. Surface stresses in 3D scaffold reconstructions, obtained from high resolution microcomputed tomography images are calculated for both boundary condition types and compared with the actual whole scaffold values via image-based CFD simulations. It is found that, both boundary conditions follow the same spatial surface stress patterns as the whole scaffold simulations. However, they under-predict the absolute stress values approximately by a factor of two. Moreover, it is found that the error grows with higher scaffold porosity. Additionally, it is found that the PBC always resulted in a lower error than the WBC.
In a second tissue engineering study, the dependence of culture time on the distribution and magnitude of fluid shear in tissue scaffolds cultured under flow perfusion is investigated. In the study, constructs are destructively evaluated with assays for cellularity and calcium deposition, imaged using µCT and reconstructed for CFD simulations. It is found that both the shear stress distributions within scaffolds consistently increase with culture time and correlate with increasing levels of mineralized tissues within the scaffold constructs as seen in calcium deposition data and µCT reconstructions.
In the thrombogenesis application, detailed analysis of time lapse microscopy images showing yielding of thrombi in live mouse microvasculature is performed. Using these images, image-based CFD modeling is performed to calculate the fluid-induced shear stresses imposed on the thrombi’s surfaces by the surrounding blood flow. From the results, estimates of the yield stress (A critical parameter for quantifying the extent to which thrombi material can resist deformation and breakage) are obtained for different blood vessels. Further, it is shown that the yielding observed in thrombi occurs mostly in the outer shell region while the inner core remains intact. This suggests that the core material is different from the shell. To that end, we propose an alternative mechanism of thrombogenesis which could help explain this difference.
Overall, the findings from this work reveal that image-based modeling is a versatile approach which can be applied to different biomedical application areas while overcoming the difficulties associated with conventional modeling
Shear-promoted drug encapsulation into red blood cells: a CFD model and μ-PIV analysis
The present work focuses on the main parameters that influence shear-promoted encapsulation of drugs into erythrocytes. A CFD model was built to investigate the fluid dynamics of a suspension of particles flowing in a commercial micro channel. Micro Particle Image Velocimetry (μ-PIV) allowed to take into account for the real properties of the red blood cell (RBC), thus having a deeper understanding of the process. Coupling these results with an analytical diffusion model, suitable working conditions were defined for different values of haematocrit
Book of Abstracts 15th International Symposium on Computer Methods in Biomechanics and Biomedical Engineering and 3rd Conference on Imaging and Visualization
In this edition, the two events will run together as a single conference, highlighting the strong connection with the Taylor & Francis journals: Computer Methods in Biomechanics and Biomedical Engineering (John Middleton and Christopher Jacobs, Eds.) and Computer Methods in Biomechanics and Biomedical Engineering: Imaging and Visualization (JoãoManuel R.S. Tavares, Ed.).
The conference has become a major international meeting on computational biomechanics, imaging andvisualization. In this edition, the main program includes 212 presentations. In addition, sixteen renowned researchers will give plenary keynotes, addressing current challenges in computational biomechanics and biomedical imaging.
In Lisbon, for the first time, a session dedicated to award the winner of the Best Paper in CMBBE Journal will take place.
We believe that CMBBE2018 will have a strong impact on the development of computational biomechanics and biomedical imaging and visualization, identifying emerging areas of research and promoting the collaboration and networking between participants. This impact is evidenced through the well-known research groups, commercial companies and scientific organizations, who continue to support and sponsor the CMBBE meeting
series. In fact, the conference is enriched with five workshops on specific scientific topics and commercial software.info:eu-repo/semantics/draf
MRI Evaluation of Injectable Hyaluronic Acid Hydrogel Therapy to Attenuate Myocardial Infarct Remodeling
Left ventricular (LV) remodeling following myocardial infarction (MI) leads to maladaptive processes that often progress to heart failure. Injectable biomaterials can alter the mechanical signaling post-MI to limit this progression. To design optimal therapies, noninvasive techniques are needed to elucidate the reciprocal interaction between the injected material and the surrounding myocardial tissue. Towards this goal, the general hypothesis of this dissertation was that magnetic resonance imaging (MRI) can be used to characterize the properties of injectable materials once delivered to the myocardium and evaluate the temporal effects of injectable materials on myocardial tissue properties post-MI. To test this hypothesis, injectable hyaluronic acid (HA) hydrogels were developed with a range of gelation, degradation and mechanical properties by altering the initiator concentration, macromer modification, and macromer concentration, respectively. Non-contrast MRI was then used to characterize the properties (e.g., distribution, chemical composition) of injectable HA hydrogels in myocardial explants. Altering hydrogel gelation led to differences in distribution in myocardial tissue, as quantified by T2-weighted MRI. As an alternative to conventional (i.e.T2-weighted) MRI where contrast depends on differences in MR properties and thus, is non-specific for the material, chemical exchange saturation transfer (CEST) MRI was used to specifically image hydrogels based on their functional (i.e. exchangeable proton) groups. CEST contrast correlated with changes in material properties, specifically macromer concentration. Furthermore, CEST MRI was shown to simultaneously visualize and discriminate between different injectable materials based on their unique chemistry. Finally, the effect of injectable HA hydrogels on myocardial tissue properties was temporally evaluated in a porcine infarct model up to 12 weeks post-MI. Outcome assessment using MRI (e.g. cine, late-gadolinium enhancement, and spatial modulation of magnetization MRI) and finite element (FE) modeling demonstrated that hydrogel therapy led to improved global LV structure and function, increased wall thickness, preserved borderzone contractility, and increased infarct stiffness, respectively. This work demonstrates that MRI can be used to simultaneously study hydrogel properties after injection into the myocardium and evaluate the ability of injectable hydrogels to alter myocardial tissue properties to ultimately improve cardiac outcomes and enable future optimization of biomaterial therapies to attenuate adverse remodeling post-MI
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