| 1. |
- Luo, Jun
(författare)
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Calcium Phosphate Based Biomaterials for Bone Augmentation
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Basic (apatite-based) calcium phosphate cements (CPCs), and acidic (brushite and monetite-based) CPCs are used as bone replacement materials because of their bioactivity, mouldability and ability to harden in place. However, their application is limited by their inherent brittleness and difficulties related to their handling. The current thesis aimed to provide solutions to these limitations.To assess the baseline, the mechanical properties of two promising experimental and two commercially available apatite and brushite cements were investigated. The two experimental CPCs exhibited significantly higher mechanical strengths than the two commercially available ones, warranting further advancement of the former towards clinical use.The setting reaction of brushite cements was, for the first time, quantitatively studied in the first seconds and minutes, using synchrotron X-ray diffraction. The reaction was found to include a fast nucleation induction period (<9 s), nucleation (<18 s), brushite content increase and setting completion. The effect of the commonly used retardant citric acid – which usually also gives stronger brushite cements - was also evaluated, providing important information for further cement development. To overcome complicated usage and short shelf life of acidic CPCs, a ready-to-use acidic CPC was developed by mixing a monocalcium phosphate monohydrate (MCPM) paste and a β-tricalcium phosphate (β-TCP) paste with suitable amounts of citric acid. The CPC showed adequate shelf life, good cohesion and mechanical performance.To mitigate against the brittle behavior of CPCs, i) poly(vinyl alcohol) fibres were used to reinforce apatite cements, significantly improving the apatite matrix’s toughness and resistance to cracking; ii) injectable, ready-to-use organic-inorganic composites with partly elastomeric compression behavior were designed based on silk fibroin hydrogels and acidic calcium phosphates, and their ability for antibiotic drug delivery was assessed. In summary, insights into the functional properties of currently available CPCs as well as the setting process of brushite cements were gained and several new calcium phosphate-based formulations were developed to overcome some of the drawbacks of traditional CPCs. Further studies, in particular of the biological response, are needed to verify the potential of the developed materials for future use in the clinical setting.
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| 2. |
- Zhou, Yijun, 1993-
(författare)
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Mechanical optimization of orthopaedic bone screw constructs
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Orthopaedic screw implants are crucial in surgical procedures for bone structures, with a longstanding issue being screw loosening. Improving screw stability requires an enhanced understanding of the bone-implant interactions and associated failure mechanisms. This knowledge can be used to optimize screw designs.In this thesis, a first step towards this end was taken through the development of enhanced trabecular bone models. Due to the trabecular bone's complex structure and the difficulties in obtaining micro-structural information, we proposed a numerical model based on Voronoi tessellation to mimic the trabecular bone morphology across varying porosities. This model's mechanical properties aligned well with analytical formulas and finite element modelling of real bone specimens, showing strong agreement with experimental results.Further investigation into screw-trabecular bone interaction was carried out using two numerical models. The explicit finite element models were able to replicate experimental screw push-in results. While only one of the models accounted for the screw insertion step, both models showed strong congruence with key experimental results. The two-step simulation however led to a more physically plausible Young’s modulus for trabecular bone material.Utilizing a validated numerical model, a numerical optimization process was initiated, where novel screw designs were proposed. Several neural network surrogate models were introduced, reducing evaluation costs while maintaining prediction accuracy. We found that screw insertion position, trabecular bone porosity, and orientation were significant factors, explaining about 96% of the variance in predicted response. Furthermore, a neural network workflow was developed to generate super-resolution trabecular bone models from clinical CT data, improving accuracy by up to 700% both morphologically and mechanically, using micro-CT models as a benchmark.Lastly, the potential enhancement of screw's primary stability was explored, by injection of hyaluronic acid mixed with hydroxyapatite particles. The augmentation effect was influenced by the hydroxyapatite particles' size and shape. Considering that these particles can also promote bone growth, a particle-laden hydrogel injection could potentially enhance screw stability throughout its lifespan.In conclusion, this study proposed methods to elucidate bone-implant interaction and enhance screw stability in trabecular bone, encompassing trabecular bone modelling, bone-screw interaction investigations, screw geometric optimization, super-resolution trabecular bone model generation from clinical CT data, and hydrogel optimization for stability. The results provide an enhanced understanding as well as optimization of complex geometric interactions, and could lead to future enhancements of clinical practice in terms of screw stability.
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| 3. |
- Carlsson, Jenny, 1984-
(författare)
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On Crack Dynamics in Brittle Heterogeneous Materials
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Natural variation, sub-structural features, heterogeneity and porosity make fracture modelling of wood and many other heterogeneous and cellular materials challenging. In this thesis, fracture in such complicated materials is simulated using phase field methods for fracture. Phase field methods have shown promise in simulations of complex geometries as well as dynamics and require few additional parameters; only the material toughness and a length parameter, determining the width of a regularised crack, are needed.First, a dynamic phase field model is developed and validated against experiments performed on homogeneous brittle polymeric materials, wood fibre composites and polymeric materials with different hole patterns. Then, a high-resolution model of wood is developed and related to experiments, this time without considering fracture. Attention is finally focussed on high-resolution numerical analyses of fracture in wood and other cellular microstructures, considering both heterogeneity and relative density.The phase field model is found to reproduce crack paths, velocities and energy release rates well in homogeneous samples both with and without holes. In more complicated heterogeneous and porous materials, the model is also able to simulate crack paths, but the interpretation of the length scale is complicated by the inherent lengths of the micro-structural geometry. In sum, the thesis points to possibilities with the proposed method, as well as limitations in our current understanding of both quasistatic and dynamic fracture of heterogeneous and cellular materials. The findings of this thesis can contribute to an improved understanding of fracture in such materials.
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| 4. |
- Corrêa Filho, Luimar N., 1985-
(författare)
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Functional properties of silicon nitride based materials for joint applications
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Total hip and total knee replacements are generally successful procedures for patients suffering with pain due to bone fracture or diseases affecting the joints. However, the materials that are commonly used still have limitations. In particular, corrosion products and wear debris may give rise to negative body reactions.In this thesis, silicon nitride based materials were investigated for use in joint implants, namely as a coating for e.g. femoral heads and the metallic modular taper junction in hip implants, as well as a bulk bioceramic for joint applications. One of the main advantages of these materials is the potential to dissolve slowly in aqueous solutions, releasing only biocompatible ions.To understand the mechanical and wear properties of these materials, thin film coatings were deposited using magnetron-based techniques onto Si wafers and a CoCrMo alloy, the latter frequently used in biomedical implants. Coatings up to 8.8 µm thick were deposited on 2D flat discs as well as full 3D implant heads, following a CrN interlayer for improved adhesion. The chemical composition, microstructure, surface roughness, adhesion, wear resistance, and dissolution properties of the coatings were evaluated as a function of substrate rotation, bias voltage, target power as well as the addition of different elements.Results show that it is possible to produce coatings with mechanical properties and a wear performance similar to bulk ceramics and other ceramic coatings already evaluated in vivo. It was evident that a high coating density is needed, to avoid premature failure in an in vivo environment. The coating density, and stability over time in solution, was found to increase when a higher target power and process heating were used.New bulk silicon nitride materials containing only biocompatible additives, were evaluated for potential use in joint applications by wear tests for the first time, showing very low wear rates of the counter material.Silicon nitride coatings and bulk materials tested in this work showed promising results for further investigation and a basis for future application in joint bearings.
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| 5. |
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| 6. |
- Ghandour, Salim
(författare)
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Novel Materials and Implant Designs for the Treatment of Degenerative Disc Disease
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The overarching objective of this thesis was to develop intervertebral implants for degenerated discs through design, fabrication, and mechanical validation. The research had four primary aims, each addressing different facets of implant development.The first aim was to design a structurally optimized fusion intervertebral cage capable of accommodating weak bioactive materials. Topology optimization was employed to design cages using titanium and calcium phosphate. The cage’s integrity was verified using finite element simulations, fabricated using additive manufacturing, and validated using ASTM F2077. Imaging techniques were utilized to assess the quality of the produced cages. These evaluations confirmed the mechanical reliability of the produced cage, able to incorporate around 75% in volume of a bioactive calcium phosphate material, protected by the titanium.The second aim was to develop a clinically relevant degeneration model for the biomechanical evaluation of percutaneous cement discoplasty (PCD). To this end, voids were generated in ovine functional spinal units (FSUs) using papain. The results were compared with clinical data where parameters such as void volume percentage, disc height, and morphology of the induced injury were assessed. FSUs were treated with PCD using bone cement, and mechanically evaluated under healthy, injured, and treated conditions to determine if PCD could stabilize the spinal segment. The void induced showed similar parameters compared to the clinical data. Further, the stability of the spine was significantly reduced after degeneration and restored after treatment, highlighting the effectiveness of the degeneration method and PCD treatment.The third aim was to evaluate the suitability of novel bone cements for their use in PCD. This study examined the tensile and fatigue properties of a low-modulus cement (VSLA) primarily intended for vertebroplasty. The formulation was tested in tensile and fatigue. VSLA showed a significant decrease in tensile and fatigue properties when compared to commercial cements. This study set a baseline for future low-modulus cements that may be tested for use in PCD.The fourth aim was to evaluate an alternative cement due to the low viscosity of VSLA, which may not be suitable for discoplasty. This study assessed the fatigue and long-term properties of a high-viscosity low-modulus cement (hv-LA-PMMA). The hv-LA-PMMA showed a significant reduction of mechanical and fatigue properties when compared to its commercial base. Notably, the fatigue properties were similar to those of the annulus fibrosus in the disc. Additionally, its high viscosity renders it a promising alternative to the bone cements currently utilized in PCD.In conclusion, this thesis successfully addressed the design, fabrication, and mechanical validation of two types of intervertebral implants for degenerated discs. The research outcomes contribute with valuable insights into the design of fusion cages, a degeneration model to evaluate PCD, and the assessment of low-modulus cements for use in PCD.
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| 7. |
- Hallberg, Gunilla
(författare)
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Effects of Endogenous and Exogenous Hormones on the Female Breast : With Special Reference to the Expression of Proteoglycans
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis aims to study the effects of endogenous and exogenous hormones and mammographic breast density (BD) on cellular markers in non-cancerous female breast tissue. Women on the waiting list for breast reduction plastic surgery were recruited (n = 79), and randomized to 2 months of hormone therapy or no therapy before surgery. The women had a mammogram and a needle biopsy 2 months before surgery and tissue samples were obtained at the operation. In premenopausal women, estrogen receptor (ER)α levels were associated with age (p = 0.0002), were similar in the follicular and luteal phases of the menstrual cycle and were higher in parous than in nulliparous women (p = 0.009). Current smokers had lower PR levels than non-smokers (p = 0.019). Women on oral contraception had lower ERα (p = 0.048) and PR (p = 0.007) levels than women in the follicular phase. The ERα levels did not differ significantly between postmenopausal estrogen and estrogen-progestogen users, but PR levels were lower among estrogen-progestogen users (p = 0.03). We found lower expression of the genes for decorin and syndecans 1 and 4 in the luteal phase than in the follicular phase, among parous women. Protein levels of the androgen receptor, syndecan-4 and decorin was lower in premenopausal women who were using oral contraceptives (OC) than in those in the follicular phase (p = 0.002 - 0.02), whereas no significant differences between OC use and the luteal phase were found. In premenopausal women, BD was negatively associated with age and body mass index but was similar for the menstrual phases. Breast density was associated with genetic expression of the androgen receptor and remained significant after adjustment for age (rs = 0.56; p = 0.04). After adjustement for age, breast density was also marginally associated with expression of the caspase 3 gene (0.55; 0.053). However, protein levels of caspase 3 was negatively associated (-0.61; 0.03).
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| 8. |
- Lewin, Susanne
(författare)
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Functional Aspects of Cranial Implants : Mechanical and Regenerative Properties
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In several neurosurgical procedures, the skull must be temporarily opened. The resulting bone defect can subsequently be reconstructed with a cranial implant. However, the complication rate of this surgical procedure is high (~20%). The most common complication for cranial implants is infection. Currently, the most frequently used implant materials are titanium alloys, PMMA or PEEK. An improved clinical outcome – in terms of increased bone regeneration, vascularization and soft tissue compatibility – could possibly be obtained through the use of bioactive and osteoconductive materials such as calcium phosphates (CaP).This thesis focuses on CaP–titanium composite (CaP–Ti) implants. This recently developed implant type is increasingly used with a promising outcome. However, a thorough understanding of its functional properties is lacking, something that is of high importance for their clinical use, but also for future biomaterial development. The overall aim of this thesis is to increase the knowledge of the in vivo functional aspects of CaP–Ti composite implants, with a specific focus on the mechanical and regenerative properties.The mechanical properties of the implant were investigated experimentally and numerically at quasi-static and impact loading rates. An important finding was that the titanium structure makes the CaP–Ti implant capable of cerebral protection in impact situations comparable to the one that was tested. Moreover, the mechanical response of the CaP–Ti implants could be predicted by the developed numerical models at both quasi-static and impact loading rates. The developed numerical framework makes an important contribution to future evaluations of patient-specific CaP–Ti cranial implant designs in various loading scenarios. A comparison of two additive manufacturing (3D-printing) processes demonstrated that lower geometrical accuracy and higher surface roughness made electron beam produced implants inferior in terms of mechanical strength, as compared to laser melted implants.In order to assess the regenerative properties, the volumetric balance of the implant was investigated by CT in ten patients. After one year, the total volume of the implant had decreased – mainly at the outside of the implants in the direction of the scalp. However, all patients had a volumetric increase at the interface between the implant and the bone defect. In a histological analysis of a retrieval specimen from one of the patients, the volumetric increase could be confirmed as bone regeneration, and the decrease as CaP degradation. Remodeling of the CaP into bone was also observed, but was not detected in the clinical CT. In retrieval specimens from an animal study, it was found that correlation of some µCT cross-sections to histology can result in improved and more robust quantitative µCT evaluations.
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| 9. |
- Persson, Gunilla Almström, 1959-
(författare)
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Perspektiv i polisprotokoll
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The subject of this study is perspective in police reports. The overall aim is to introduce new tools for analysing perspective in written narratives. The material consists of reports based on different accounts of the same conflict from a number of people (the suspect, the injured part and witnesses), that is, different versions of the same sequence of events. The study begins with a theoretical discussion of perspective in literary texts and of some characteristics of the police reports examined. Two tools are developed to analyse linguistic means for identifying perspective.The first analytical tool can be placed within the framework of cognitive semantics. Analysis here concerns seeing space differently and having different limits in one’s way of experiencing the sequence of events. This conceptualisation of the focaliser (the person whose perspective is reported) is realised in the text through certain spatial expressions associated with the concept of centre. To analyse the centres chosen, the image schema centre–periphery is used in examining instances of the adverbs fram and bort and their derivations.The second analytical tool can be placed within the theoretical framework of dramaturgy. Analysis here concerns perceiving the dramatic development of events differently, that is, dramatic patterns in the different versions of the conflict and which character is given the most active role in it. The differences can be seen in the focaliser’s choice of events and how aggression is consciously or unconsciously described in terms of how different characters cause the conflict to escalate.The hypothesis being tested is whether the suspect’s perspective is discernible in the report of the suspect’s account. The hypothesis is confirmed. The study shows that the tools introduced work successfully in the analysis of perspective. Both analyses yield results, which in both cases can be validated.
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| 10. |
- Robo, Céline
(författare)
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Bone-compliant cements for vertebral augmentation
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Acrylic bone cement based on poly(methyl methacrylate) (PMMA) is commonly used during vertebral augmentation procedures for the treatment of osteoporosis-induced vertebral compression fractures. However, the high stiffness of the cement compared to that of the surrounding trabecular bone is presumed to facilitate the formation of new fractures shortly after surgery. The aim of the thesis was to develop and evaluate a PMMA-based bone cement that better matches the mechanical properties of vertebral trabecular bone. To fulfill this objective, different compounds were added to the initial formulation of bone cement to modify its functional properties. Linoleic acid (LA) was found to give the best combination of strength and stiffness without negative effects on the handling properties and its use was therefore further investigated. In particular, different application-specific mechanical properties of LA-modified cement as well as itsin vivoperformance in an ovine model were assessed. In summary, LA-modified cement exhibited bone-compliant mechanical properties immediately after incorporation of the additive, as well as adequate handling properties, in particular a lower polymerization temperature and appropriate setting time. The screw pullout strength from low-modulus cement was substantially reduced compared to regular PMMA cement, but comparable to some calcium phosphate based cements. The fatigue limit of LA-modified cement was considerably lower compared to regular PMMA bone cement when tested in physiological solution, but still higher than stresses measured in the spine during daily activities. The modified cement displayed similar inflammatory response in vivoto conventional cement, with no evidence of additional cytotoxicity due to the presence of LA. Finally, it was possible to sterilize the additive without significantly compromising its function in the PMMA cement.The results from this thesis support further evaluation of the material towards the intended clinical application.
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