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- Bondesson, Johan, 1991
(författare)
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Modeling of Intraluminal Surfaces of Thoracic Aortas
- 2020
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Vascular diseases are getting more and more common as a result of modern-day lifestyle and the fact that the population is getting older. One of the newest treatments for vascular diseases such as aneurysms and dissections is endovascular repair with endografting. This treatment uses a fabric covered metallic structure that is implanted using a minimally invasive approach to serve as an artificial vessel in a damaged region. To ensure that the interventions are successful, the endograft must be placed in the correct location, and be designed to sustain the hostile biological, chemical, and mechanical conditions in the body for many years. To accurately describe the complex mechanical conditions of the intraluminal surfaces of diseased blood vessels inside the body, this thesis presented a segmentation and quantification methodology for a natural and intuitive vessel surface description. The thesis also included some important clinical applications, all based on non-invasive temporal imaging. The results emphasized the need for explicit surface curvature quantification, as compared to relying solely on centerline curvature and estimation methods. Methods for preoperative prediction of endograft malapposition severity based on geometric analysis of thoracic aortic surfaces were introduced. Finally, a multiaxial dynamic analysis of cardiac induced thoracic aortic surface deformation showed how a thoracic endovascular aortic repair is a↵ecting the deformations of the thoracic aorta. Thus, the work presented in this thesis contributes by giving surgeons a tool to use in their treatment planning to minimize complications. Moreover, this method provides more nuanced boundary conditions so that endograft manufacturers can improve their designs to improve the quality of life for the treated patients.
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- Fredriksson, Camilla, 1969-
(författare)
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Keratinocytes in tissue engineering of human skin: invitro and in vivo studies
- 2008
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Full thickness wounds, such as deep burns, need restoration of both the dermal and epidermal layers of the skin. In normal wound healing, re-epithelialization occurs by migration and proliferation of keratinocytes from the wound edges and by differentiation of stem cells from remaining hair follicles. Restoration of dermis occurs by influx of growth factors secreted by macrophages, platelets, and fibroblasts; by fibroblast proliferation and subsequent synthesis and remodeling of collagenous dermal matrix. In the case of full-thickness acute burn injuries and chronic wounds (e.g. pressure ulcers, venous ulcers and diabetic foot ulcers), these processes are defective. With the principles of tissue engineering in mind (to correct, improve and maintain tissues and their functions), researchers have developed promising materials and methods to make it possible to restore either the dermal (Integra® DRT, Alloderm®) or the epidermal layer (split thickness skin grafts (STSG), cultured epithelial autografts (CEA), autologous keratinocytes in single cell suspension). It is now well established that superior results are obtained if both dermal and epidermal components are combined, for example in a bilayered skin equivalent. Apligraf® is recommended for use on venous ulcers and is the only bilayered living skin equivalent currently approved by the FDA. Studies on different factors affecting the wound healing capacity as well as techniques in use provide valuable information for further development.In this licentiate thesis, we evaluated different transplantation techniques for delivering cultured human keratinocytes in single cell suspension, a measure becoming more frequently used in addition to STSG and CEA for restoring the epidermal layer of the skin. We found that the pressure device, commonly used to spray cell suspension onto the wound with pressures as high as 200 kPa, killed around 0% of the cells. In comparison, an ordinary syringe with the attachment of a spray nozzle showed almost 90% viable cells post transplantation and provided an equally good distribution of the cell suspension.We also studied different silver containing dressings regarding silver accumulation in human skin. In addition, we graded the re-epithelialization to evaluate whether the dressings caused any delay in the wound healing process. We found that the silver dressings tested, with few exceptions, caused dermal accumulation of silver, primarily aggregated around blood vessels. We could also show that most of the dressings had negative effect on the re-epithelialization.For the restoration of the dermal layer of the skin, Integra® DRT functions as a scaffold for guided tissue regeneration of the dermis. We had the possibility to study a case of necrotizing fasciitis were the treatment consisted of the use of Integra® DTR together with sub-atmospheric pressure (after initial surgical debridement) and later transplantation of split thickness skin grafts. This measure proved to be safe as well as giving satisfactory pliable and aesthetically acceptable result.
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- Johansson, Johannes, 1977-
(författare)
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Thermocoagulation in Deep Brain Structures : Modelling, simulation and experimental study of radio-frequency lesioning
- 2006
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Radio-frequency (RF) lesioning is a method utilising high frequency currents for thermal coagulation of pathological tissue or signal pathways. The current is delivered from an electrode with a temperature sensor, permitting control of the current at a desired target temperature. In the brain RF-lesioning can e.g. be used for severe chronic pain and movement disorders such as Parkinson’s disease. This thesis focuses on modelling and simulation with the aim of gaining better understanding and predictability of the lesioning process in deep brain structures. The finite element method (FEM) together with experimental comparisons was used to study the effects of electrode dimensions, electrode target temperature, electric and thermal conductivity of the brain tissue, blood perfusion and cerebrospinal fluid (CSF) filled cysts. Equations for steady current, thermal transport and incompressible flow were used together with statistical factorial design and regression analysis for this purpose.Increased target temperature, electrode tip length and electrode diameter increased the simulated lesion size, which is in accordance with experimental results. The influence of blood perfusion, modelled as an increase in thermal conductivity in non-coagulated tissue, gave smaller simulated lesions with increasing blood perfusion as heat was more efficiently conducted from the rim of the lesion. If no consideration was taken to the coagulation the lesion became larger with increased thermal conductivity instead, as the increase in conducted heat was compensated for through an increased power output in order to maintain the target temperature. Simulated lesions corresponded well to experimental in-vivo lesions.The electric conductivity in a homogeneous surrounding had little impact on lesion development. However this was not valid for a heterogeneous surrounding. CSF-filled cysts have a much higher electric conductivity than brain tissue focussing the current to them if the electrode tip is in contact with both. Heating of CSF can also cause considerable convective flow and as a result a very efficient heat transfer. This affected simulated as well as experimental lesion sizes and shapes resulting in both very large lesions if sufficient power compared to the cysts size was supplied and very small lesions if the power was low, mitigating the heat over a large volume.In conclusion especially blood perfusion and CSF can greatly affect the lesioning process and appear to be important to consider when planning surgical procedures. Hopefully this thesis will help improve knowledge about and predictability of clinical lesioning.
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- Kolar, Mallappa K
(författare)
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The use of adipose derived stem cells in spinal cord and peripheral nerve repair
- 2014
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Clinically, injuries affecting the spinal cord or peripheral nerves can leave those affected with severe disability and, at present, there are limited options for treatment. Peripheral nerve injury with a significant gap between the proximal and distal stumps is currently treated with autologous nerve grafting but this is limited by availability of donor nerve and has associated morbidities. In contrast, injuries to the spinal cord lead to an inhibitory environment caused by the glial cells and thereby, limit potential axonal regeneration. This thesis investigates the effects of human adipose derived stem cells (ASC) on regeneration after peripheral nerve and spinal cord injury in adult rats.Human ASC expressed various neurotrophic molecules and growth factor stimulation of the cells in vitro resulted in increased secretion of BDNF, GDNF, VEGF-A and angiopoietin-1 proteins. Stimulated ASC also showed an enhanced ability to induce capillary-like tube formation in an in vitro angiogenesis assay. In contrast to Schwann cells, ASC did not induce activation of astrocytes and supported neurite outgrowth from the adult rat sensory DRG neurons in culture.In a peripheral nerve injury model, ASC were seeded into a fibrin conduit, which was used to bridge a 10 mm rat sciatic nerve gap. After 2 weeks, ASC enhanced GAP-43 and ATF-3 expression in the spinal cord, reduced c-jun expression in the DRG and increased the vascularity of the fibrin nerve conduits. The animals treated with stimulated ASC showed an enhanced axon regeneration and reduced caspase-3 expression in the DRG.After transplantation into the injured C3-C4 cervical spinal cord. ASC continued to express neurotrophic factors and laminin and stimulated extensive ingrowths of 5HT-positive raphaespinal axons into the trauma zone. In addition, ASC induced sprouting of raphaespinal terminals in C2 contralateral ventral horn and C6 ventral horn on both sides. Transplanted cells also changed the structure and the density of the astroglial scar. Although the transplanted cells had no effect on the density of capillaries around the lesion site, the reactivity of OX42-positive microglial cells was markedly reduced.
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- Tse, Kai-Hei
(författare)
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Mechanisms and improvements of cell transplantation for nerve repair
- 2011
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Trauma to the nervous system is a frequent clinical problem and new approaches to nerve repair are required. Autologous cell transplantation together with a suitable scaffold material could be used to create a bio-active artificial nerve graft to enhance regeneration. The work presented in this licentiate thesis attempts to improve both the biomaterial and cellular components of this repair strategy. In the first study, by using common biodegradable polyesters, namely poly-ε-caprolactone (PCL) and poly -L,D- lactic acid (PLA), a thin film scaffold prototype was fabricated by using a solvent-evaporation method. These scaffolds, with thicknesses of approximately 10-20 µm, exhibited a heterogenous but continuous surface topography decorated with pore/pits of regulated sizes. The sizes of the pore/pits ranged from 0.5 to 30 µm2and could be modulated by varying the ratios of PLA and PCL. Biocompatibility of these scaffolds was demonstrated by using adipose derived stem cells (ADSC) differentiated into a Schwann cell-like phenotype (dADSC), which showed attachment and proliferation on the films, maintenance of glial cell markers expression and enhancement of neurite outgrowth in co-culture with dorsal root ganglia (DRG) neurons. Transplantation of cells for nerve injuries remains sub-optimal due to their limited survival rates. In the second study, a chemical ischemia model (metabolically induced by sodium azide and 2-deoxyglucose) was established to investigate the differential effects of ischemia and serum deprivation on mesenchymal stem cells (MSCs). MSCs were more suseptible to combined than individual blockade of glycolysis and oxidative phosphorylation. Apoptotic and autophagy pathways were activated in the MSCs. Chemical ischemia or serum withdrawal alone induced a similar amount of cell death with significantly different intracellular ATP maintenance; but their effects were additive. The levels of various neurotrophin extracellular matrix and angiogenic factors expressed by the cells were shown to be differentially affected by ischemia but unaffected by changes in serum level. Stem cells isolated from both adipose tissue (ADSC) and bone marrow (BMSC) reacted similarly under these conditions. This chemical ischemia model will enable future screening of pharmacological agents to enhance the survival of MSCs under stress conditions. The mechanism underlying the neurotrophic potential of MSCs is unknown. In the third study in this thesis it is hypothesised that MSCs, upon stimulation with different growth factors, could produce brain derived neurotrophic factor (BNDF) with a similar molecular mechanism to that described in the nervous system. Within 24 hours of stimulation, ADSC and BMSC showed high secretion levels of BDNF, and these cells were able to enhance axonal outgrowth in DRG neurons at levels similar to long-term differentiated MSCs. Both the neuronal activity dependent promoterBDNFexon IV, along with full length protein encodingBDNFexon IX, were up-regulated upon stimulation.BDNFgating transcription factor, cyclic cAMP responsive element binding (CREB) protein, was also found to be activated but blocking of CREB phosphorylation with the small molecule inhibitor H89 did not suppress expression of BDNF protein suggesting compensatory pathways are involved. In summary, these studies indicate that MSCs are compatible with polyester based microporous scaffolds but the cells are highly susceptible to the stress conditions mimicking the hostile milieu at a nerve injury site. Preliminary studies hint at the molecular mechanism regulation BDNF expression in MSC and imply the interactions between MSCs and axons may play a role in the neurotrophic activity of the stem cells.
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