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- 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. |
- 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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| 3. |
- Tummala, Gopi Krishna, 1986-
(författare)
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Hydrogels of Poly(vinyl alcohol) and Nanocellulose for Ophthalmic Applications : Synthesis, Characterization, Biocompatibility and Drug Delivery Studies
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Hydrogels are commonly used materials in ophthalmic care as contact lenses, bandage lenses, corneal implants, and cornea regeneration scaffolds. Hydrogels can be produced by physical, chemical, or radiation crosslinking of hydrophilic polymers. Poly(vinyl alcohol) (PVA) is a hydrophilic polymer that has been long known to the scientific community and is used in ophthalmic formulations.In this thesis, PVA was reinforced with nanocellulose to obtain self-standing hydrogels. Cryo-gelation technique was used to obtain transparent hydrogels from PVA dissolved in DMSO-water mixed solvent. The properties of these hydrogels were analyzed to explore the possibility of their application for ophthalmic use as a drug delivery vehicle and as cornea regeneration implant.The results indicate that oxidized nanocellulose can be combined with PVA to produce transparent, elastic, macroporous and high-water content hydrogel lenses. The water-filled macroporous structure of these hydrogels aids with oxygen transport and can enhance comfort while worn. The developed hydrogel also features moderate UV-light blocking properties in addition to high transparency. Furthermore, it was observed that the light scattering due to surface roughness of the hydrogel increases with measurement time, due to the rapid evaporation of the water layer from the surface of the hydrogel film.Mechanical analysis results revealed that the hydrogels exhibited a strain-induced stiffening behavior, which is usually noticed in hyper-elastic materials and collagenous soft tissues. The results of this study suggest that in order to mimic collagenous behavior, the material should possess high water content and a specific structural architecture combining soft and rigid elements as building blocks.Furthermore, PVA-CNC composite hydrogel showed no toxic effects on the corneal cells in both direct and indirect contact studies. It was found that the hydrogel promoted cell attachment and was stable when sutured ex vivo to a porcine excised cornea.To study enzyme-triggered drug release, hydrogel lenses loaded with chitosan-poly(acrylic acid) nanoparticles were exposed to lysozyme, an enzyme present in the eye. Nanoparticles were shown to disintegrate due to the hydrolysis of chitosan chains by lysozyme. Overall, with these distinctive properties, PVA-CNC hydrogel has great potential as an ophthalmic biomaterial for therapeutic and cornea regeneration applications.
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| 4. |
- Wu, Dan, 1990-
(författare)
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Mechanical analyses of trabecular bone and its interaction with implants
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Bone substitute materials or implants are commonly used in the surgical treatment of bone fractures. However, severe complications are sometimes reported. In order to improve fracture treatment where the interior, porous trabecular bone is involved, it is important to better understand the mechanical properties of this bone and how it interacts with the substitutes/implants, and this was the aim of this thesis.Since one of the key mechanical properties of trabecular bone, i.e. the elastic moduli at the tissue level, was not consistently reported in the literature, the results from four widely applied methods were first summarized and presented in a review paper.Furthermore, to improve the analysis of the mechanical behavior of bone and its interaction with implants, a new digital volume correlation (DVC) technique was proposed based on higher-order finite elements.We further proposed a method to estimate the elastic modulus at the tissue level by compression of single trabeculae within a synchrotron radiation micro-computed tomograph (SRµCT). Full-field displacements were estimated by DVC, which also provided boundary conditions for a finite element model. The proposed method shows potential to estimate trabecular mechanical properties at the tissue level.Further, strains and cracks of a trabecular structure under compression till fracture were characterized at the single trabecular level, with DVC applied on high-resolution images from SRµCT.The effect of augmentation materials on the engagement of screws inserted into trabecular bone was evaluated in human femoral bone, with and without real-time SRµCT. A newly developed tissue adhesive indicated a potential benefit of this material to the primary implant stability compared to a cement and no augmentation.Finally, a trabecular structure of PLA/HA composite material was printed using a fused deposition modelling method as a preliminary step towards better synthetic models of trabecular bone. The synthetic trabecular structure was evaluated using micro-CT, compression and screw pull-out testing.In conclusion, methods to estimate strains and mechanical properties of trabecular bone were proposed, insights into interactions between trabecular bone and augmentation/implants were gained, as well as a first step towards a synthetic trabecular model, which may contribute to further mechanical analyses and/or improved clinical treatments of trabecular bone.
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| 5. |
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| 6. |
- Pettersson, Maria
(författare)
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Silicon nitride for total hip replacements
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- For more than 50 years total hip replacements have been a common and successful procedure to increase patient mobility and quality of life. The 10-year implant survival rate is 97.8%. However, for longer implantation times there are limitations linked to the negative biological response to wear and corrosion products from the currently used biomaterials.In this thesis silicon nitride (SiNx) coatings were evaluated for use in total hip replacements, on the articulating bearing surface and modular taper connections. Homogeneous, dense SiNx coatings were deposited using reactive high power impulse magnetron sputtering (HiPIMS) up to a thickness of 8 µm. The N/Si atomic ratios ranged from 0.3 to 1.1 and the coatings showed a low surface roughness. The wear rate of a SiNx coated cobalt chromium molybdenum alloy (CoCrMo) was similar to that of bulk Si3N4, and less than one 46th of uncoated CoCrMo, an alloy that is commonly used in joint replacements. Wear debris generated from SiNx coatings was round in shape, with a mean size of 40 nm, and ranged between 10 and 500 nm. Model particles, similar in size and shape as the wear debris, were soluble in simulated body fluid. The dissolution rate was higher than the expected rate of debris generation. Along with the size of the debris, which is not in the critical range for macrophage activation, this dissolution may limit negative biological reactions. The SiNx coatings also dissolved in simulated body fluid. The coating with the highest N/Si ratio exhibited the lowest dissolution rate, of 0.2 to 0.4 nm/day, while CoCrMo under the same condition dissolved at a rate of 0.7 to 1.2 nm/day. SiNx-coated CoCrMo exhibited a reduced release of Co, Cr and Mo ions into the solution by two orders of magnitude, compared to uncoated CoCrMo. Si3N4 evaluated under micro-displacement in a corrosive environment, replicating the modular taper, showed a lower corrosion current compared to common biomedical alloys. SiNx coatings may also act beneficially to reduce issues associated with this type of contact.SiNx coatings have shown several properties in a laboratory environment that are hypothesised to increase the longevity of joint replacements. The promising results encourage further evaluation closer to the clinical application of total hip replacements, in particular in the articulating bearing surface and in modular tapers.
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