| 1. |
- Ahlinder, Astrid
(författare)
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Degradable copolymers in additive manufacturing: controlled fabrication of pliable scaffolds
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Inom vävnadsregenerering är produktionen av väldefinieradematriser med en porös arkitektur av nedbrytbara polymerer av stortintresse, dessa kan nu skapas genom additiva tillverkningsprocesser. Vidadditiv tillverkning krävs ett smalt munstycke för att skapa detaljrikastrukturer och detta ställer krav på att de reologiska egenskapernaanpassat. Lägre viskositet av smältan gör de lättare att använda, men enhög molmassa krävs för tillverka matriser där de mekaniska egenskapernakan bibehållas under tiden som krävs för vävnadsregenerering. Ytterligareen utmaning uppstår när nedbrytbara polymerer används i smältbaseradadditiva tillverkningsprocesser är att termisk nedbrytning ofta reducerarmolmassan redan under produktionsfasen. För att kunna användanedbrytbara polymerer av medicinsk kvalitet i smältbaserad additivtillverkning och samtidigt minimera den termiska nedbrytningen har, idenna avhandling, reologiska fingeravtryck av nedbrytbara syntetiskapolymerer med medicinsk kvalitet använts för att bestämmaprocessparametrar. Termisk nedbrytning beroende av processparamaterar har analyserats och minimeras i två smältbaserade additivatillverkningsprocesser.En additiv tillverkningsprocess var designad där nedbrytbarapolymerer av hög molmassa kunde användas utan termisk nedbrytning närprocessparametrar hade valts utifrån polymerens egenskaper. Kunskapenom användningen av dessa polymerer inom additiv tillverkning kundeappliceras på en sampolymer som utvecklats inom forskningsgruppen förmjukvävnad, poly(ε-kaprolakton-co-p-dioxanon) för att skapa böjbaramatriser. Genom att använda reologisk analys och polymerkarakteriseringerhölls processparametrar som möjliggjorde additiv tillverkning utantermisk nedbrytning. I tillägg till val av polymer och processparametrar såkan mekaniska egenskaper också styras av den strukturella designen.Poly(ε-kaprolakton) användes som modellmaterial för att reducerastyvheten med hjälp av designen, resultatet visade att det var möjligt medmer än en faktor 10 och mjuka böjbara matriser skapades.
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| 2. |
- Biasetti, Jacopo
(författare)
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Physics of blood flow in arteries and its relation to intra-luminal thrombus and atherosclerosis
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Vascular pathologies such as Abdominal Aortic Aneurysm (AAA) and atherosclerosis are complex vascular diseases involving biological, mechanical, and fluid-dynamical factors. This thesis follows a multidisciplinary approach and presents an integrated fluid-chemical theory of ILT growth and analyzes the shear-induced migration of red blood cells (RBCs) in large arteries with respect to hypoxia and its possible role in atherosclerosis. The concept of Vortical Structures (VSs) is employed, with which a theory of uid-chemically-driven ILT growth is formulated. The theory proposes that VSs play an important role in convecting and activating platelets in the aneurysmatic bulge. In particular, platelets are convected toward the distal aneurysm region inside vortex cores and are activated via a combination of high residence times and relatively high shear stress at the vortex boundary. After vortex breakup, platelets are free to adhere to the thrombogenic wall surface. VSs also convect thrombin, a potent procoagulant enzyme, captured in their core, through the aneurysmatic lumen and force its accumulation in the distal portion of the AAA. This framework is in line with the clinical observation that the thickest ILT is usually seen in the distal AAA region. The investigation of the fluid-dynamics in arteries led to the study of the shear-induced migration of RBCs in large vessels such as the abdominal aorta and the carotid artery. Marked RBCs migration is observed in the region of the carotid sinus and in the iliac arteries, regions prone to atherogenesis. This leads to the hypothesis that oxyhemoglobin availability can decrease in the near-wall region thus contributing to wall hypoxia, a factor implicated in atherosclerosis. The thesis proposes a new potential mechanism of ILT growth, driven by fluid and chemical stimuli, which can be used to study ILT progression over physiologically relevant timeframes and be used as a framework to test new hypotheses; the thesis also provides new insights on the oxyhemoglobin availability in the near-wall region with direct inuence on atherosclerosis.
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| 3. |
- Grytsan, Andrii, 1986-
(författare)
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Abdominal aortic aneurysm inception and evolution - A computational model
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Abdominal aortic aneurysm (AAA) is characterized by a bulge in the abdominal aorta. AAA development is mostly asymptomatic, but such a bulge may suddenly rupture, which is associated with a high mortality rate. Unfortunately, there is no medication that can prevent AAA from expanding or rupturing. Therefore, patients with detected AAA are monitored until treatment indication, such as maximum AAA diameter of 55 mm or expansion rate of 1 cm/year. Models of AAA development may help to understand the disease progression and to inform decision-making on a patient-specific basis. AAA growth and remodeling (G&R) models are rather complex, and before the challenge is undertaken, sound clinical validation is required.In Paper A, an existing thick-walled model of growth and remodeling of one layer of an AAA slice has been extended to a two-layered model, which better reflects the layered structure of the vessel wall. A parameter study was performed to investigate the influence of mechanical properties and G&R parameters of such a model on the aneurysm growth.In Paper B, the model from Paper A was extended to an organ level model of AAA growth. Furthermore, the model was incorporated into a Fluid-Solid-Growth (FSG) framework. A patient-specific geometry of the abdominal aorta is used to illustrate the model capabilities.In Paper C, the evolution of the patient-specific biomechanical characteristics of the AAA was investigated. Four patients with five to eight Computed Tomography-Angiography (CT-A) scans at different time points were analyzed. Several non-trivial statistical correlations were found between the analyzed parameters.In Paper D, the effect of different growth kinematics on AAA growth was investigated. The transverse isotropic in-thickness growth was the most suitable AAA growth assumption, while fully isotropic growth and transverse isotropic in-plane growth produced unrealistic results. In addition, modeling of the tissue volume change improved the wall thickness prediction, but still overestimated thinning of the wall during aneurysm expansion.
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| 4. |
- Martufi, Giampaolo, 1980-
(författare)
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Biomechanics of abdominal aortic aneurysm:Experimental evidence and multiscale constitutive modeling
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The reliable assessment of Abdominal Aortic Aneurysm (AAA) rupture risk is critically important in reducing related mortality without unnecessarily increasing the rate of elective repair. A multi-disciplinary approach including vascular biomechanics and constitutive modeling is needed to better understand and more effectively treat these diseases. AAAs are formed through irreversible pathological remodeling of the vascular wall and integrating this biological process in the constitutive description could improve the current understanding of this disease as well as the predictability of biomechanical simulations.First in this thesis, multiple centerline-based diameter measurements between renal arteries and aortic bifurcation have been used to monitor aneurysm growth of in total 51 patients from Computer Tomography-Angiography (CT-A) data. Secondly, the thesis proposes a novel multi-scale constitutive model for the vascular wall, where collagen fibers are assembled by proteoglycan cross-linked collagen fibrils and reinforce an otherwise isotropic matrix (elastin). Collagen fibrils are dynamically formed by a continuous stretch-mediated process, deposited in the current configuration and removed by a constant degradation rate. The micro-plane concept is then used for the Finite Element (FE) implementation of the constitutive model. Finally, histological slices from intra-luminal thrombus (ILT) tissue were analyzed using a sequence of automatic image processing steps. Derived microstructural data were used to define Representative Volume Elements (RVEs), which in turn allowed the estimation of microscopic material properties using the non-linear FE.The thesis showed that localized spots of fast diameter growth can be detected through multiple centerline-based diameter measurements all over the AAA sac. Consequently, this information might further reinforce the quality of aneurysm surveillance programs. The novel constitutive model proposed in the thesis has a strong biological motivation and provides an interface with biochemistry. Apart from modeling the tissue’s passive response, the presented model is helpful to predict saline feature of aneurysm growth and remodeling. Finally, the thesis provided novel microstructural and micromechanical data of ILT tissue, which is critically important to further explore the role of the ILT in aneurysm rupture.
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| 5. |
- Miller, Christopher
(författare)
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Modelling the time-dependent, damage and fracture mechanical properties of load-bearing soft biological tissues
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Load-carrying soft biological tissues exhibit a wide range of complex time-dependent, damage, and fracture mechanical properties. An effective comprehension of such behaviour is advantageous in characterising tolerance to injury and can provide valuable insights regarding the incidence and progression of certain diseases. Improving knowledge in such areas directly benefits the successful integration of engineering concepts within the clinical workflow. Moreover, it can aid in the advancement of preventative measures, patient treatment strategies, and the optimisation of medical device design. The macroscopic material response of soft tissue is inextricably linked to the deformation of mechanically significant extracellular matrix (ECM) components such as fibrous collagen and associated constituents like proteoglycans. There is, however, a fundamental lack of understanding concerning the tensile properties of the collagenous ECM at different length scales. The inherent challenges associated with the experimental discernment of such processes have motivated the deployment of modelling strategies as an effective investigative tool. This thesis has dealt with the design of generalised constitutive descriptions that propose salient microstructural deformation, damage, and failure-related mechanisms.In Paper A, A multiscale constitutive framework based on a novel description of collagen is introduced. The description accounts for the gradual recruitment of undulated collagen fibrils and introduces proteoglycan-mediated time-dependent fibrillar sliding. Crucially, the proteoglycan deformation allows for the reduction of overstressed fibrils towards a preferential homeostatic stress. An implicit Finite Element implementation of the model uses an interpolation strategy towards collagen fibre stress determination and results in a memory-efficient representation of the model. A number of test cases, including patient-specific geometries, establish the efficiency of the description and demonstrate its ability to explain qualitative properties reported from macroscopic experimental studies of tendon and vascular tissue.In Paper B, the aforementioned description is extended such that it additionally incorporates an interfibrillar failure (fibril pull-out) mechanism. The resulting damage-induced mechanical behaviour across several length scales is showcased for the microstructurally motivated continuum damage model. Notably, a bottom-up approach is further demonstrated, whereby the model is employed in a single-element representation of the modes of fracture. A qualitative description of soft tissue rupture is accordingly attained, to which an appropriate cohesive zone model for the equivalent fracture surface is then calibrated. In doing so, a surface-based discontinuous characterisation of failure is directly derived from the upscaling of irreversible and dissipative damage mechanisms from the microscale.In Paper C, we present the novel coupling of the above continuum damage model with an embedded phenomenological representation of the fracture surface. Tissue separation is therefore accounted for through the integration of the cohesive crack concept within the partition of unity finite element method. A transversely isotropic cohesive potential per unit undeformed area is introduced that comprises rate-dependent damage evolution and accounts for mixed-mode failure. Furthermore, a novel crack initialisation procedure is detailed that identifies the occurrence of localised deformations in the continuum material and the orientation of the inserted discontinuity. Proof of principle is demonstrated via the application of the computational framework to two representative numerical simulations, illustrating the robustness and versatility of the formulation.
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| 6. |
- Tojaga, Vedad
(författare)
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On fiber network fracture mechanics and kink band formation in biocomposites
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis summarizes seven appended papers dealing with: (1) The fracture of fibrous materials, e.g., paper and paperboard, toward understanding the upper limits of paper products and eventually optimizing packaging performance in its endeavor to replace plastics with recyclable packaging; (2) The compressive failure of flax fiber composites, a promising eco-friendly alternative to synthetic composite materials, toward understanding the low compressive-compared-to-tensile strength of biocomposites, a design-limiting feature, and ultimately engineer better performing natural fiber composites for sustainable structures. (1) In Paper I, we consider an elastoplastic Timoshenko beam finite element formulation with embedded strong discontinuities in the description of multi-fracturing fibers in fiber networks, a deficiency in previous studies. Seeing that the coupled (monolithic) problem is non-convex, materializing through poor robustness and undesirable material instabilities, we present an alternating minimization (staggered) algorithm for this class of problems and thus retain a positive definite stiffness matrix. In Paper II, we propose a hybrid of monolithic and staggered solution methods for robust and computationally efficient fracture simulations, with an up to 30-fold performance gain compared to the staggered approach in the benchmark exercises. The hybrid method represents a matrix regularization technique that retains a positive definite stiffness matrix while approaching the tangent stiffness matrix of the monolithic problem. In Paper III, we develop a geometrically nonlinear Simo-Reissner beam theory with embedded strong discontinuities based on the method of incompatible modes, capturing the activation of additional fibers during loading. We show that accounting for geometrical nonlinearity in the beam formulation is necessary for direct numerical simulations of fiber networks regardless of the density. (2) In Paper IV, we formulate a multi-scale homogenization framework for layered composite materials, where we model the instantaneous constitutive behavior of the matrix and the fiber separately utilizing a combined Voigt and Reuss approximation, followed by an upscaling to the composite. Advantages include the independence of fiber rotations because it is fully defined in the known initial configuration of the composite. In Paper V, we back-calculate the compressive stress-strain response of the flax fiber from the Impregnated Fiber Bundle Test (IFBT) in compression using the rule of mixtures, necessary input data in the micromechanical description of flax fiber composites. In Paper VI, we formulate hyperelastic models for deformation plasticity into the finite strain range. One application includes mimicking the stress-strain response of the fiber and the matrix in the homogenization of layered composite materials, which we numerically verify against a micromechanical model. In Paper VII, we extend the hyperelastic model to account for fiber damage. We show numerically and experimentally through X-ray Computed Tomography (XCT) and Scanning Electron Microscopy (SEM) that fiber damage plays the utmost role in the compressive failure of flax fiber composites – it is a major determinant of the material’s compressive stress-strain response. The micromechanisms include elementary fiber crushing and intra-technical fiber splitting.
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