| 1. |
- Aulin, Cecilia, 1979-
(författare)
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Extracellular Matrix Based Materials for Tissue Engineering
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The extracellular matrix is (ECM) is a network of large, structural proteins and polysaccharides, important for cellular behavior, tissue development and maintenance. Present thesis describes work exploring ECM as scaffolds for tissue engineering by manipulating cells cultured in vitro or by influencing ECM expression in vivo. By culturing cells on polymer meshes under dynamic culture conditions, deposition of a complex ECM could be achieved, but with low yields. Since the major part of synthesized ECM diffused into the medium the rate limiting step of deposition was investigated. This quantitative analysis showed that the real rate limiting factor is the low proportion of new proteins which are deposited as functional ECM. It is suggested that cells are pre-embedded in for example collagen gels to increase the steric retention and hence functional deposition. The possibility to induce endogenous ECM formation and tissue regeneration by implantation of growth factors in a carrier material was investigated. Bone morphogenetic protein-2 (BMP-2) is a growth factor known to be involved in growth and differentiation of bone and cartilage tissue. The BMP-2 processing and secretion was examined in two cell systems representing endochondral (chondrocytes) and intramembranous (mesenchymal stem cells) bone formation. It was discovered that chondrocytes are more efficient in producing BMP-2 compared to MSC. The role of the antagonist noggin was also investigated and was found to affect the stability of BMP-2 and modulate its effect. Finally, an injectable gel of the ECM component hyaluronan has been evaluated as delivery vehicle in cartilage regeneration. The hyaluronan hydrogel system showed promising results as a versatile biomaterial for cartilage regeneration, could easily be placed intraarticulary and can be used for both cell based and cell free therapies.
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| 2. |
- Cardemil, Carina, et al.
(författare)
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Strontium-doped calcium phosphate and hydroxyapatite granules promote different inflammatory and bone remodelling responses in normal and ovariectomised rats.
- 2013
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Ingår i: PLosOne. - : Public Library of Science (PLoS). - 1932-6203. ; 8:12
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Tidskriftsartikel (refereegranskat)abstract
- The healing of bone defects may be hindered by systemic conditions such as osteoporosis. Calcium phosphates, with or without ion substitutions, may provide advantages for bone augmentation. However, the mechanism of bone formation with these materials is unclear. The aim of this study was to evaluate the healing process in bone defects implanted with hydroxyapatite (HA) or strontium-doped calcium phosphate (SCP) granules, in non-ovariectomised (non-OVX) and ovariectomised (OVX) rats. After 0 (baseline), six and 28d, bone samples were harvested for gene expression analysis, histology and histomorphometry. Tumour necrosis factor-α (TNF-α), at six days, was higher in the HA, in non-OVX and OVX, whereas interleukin-6 (IL-6), at six and 28d, was higher in SCP, but only in non-OVX. Both materials produced a similar expression of the receptor activator of nuclear factor kappa-B ligand (RANKL). Higher expression of osteoclastic markers, calcitonin receptor (CR) and cathepsin K (CatK), were detected in the HA group, irrespective of non-OVX or OVX. The overall bone formation was comparable between HA and SCP, but with topological differences. The bone area was higher in the defect centre of the HA group, mainly in the OVX, and in the defect periphery of the SCP group, in both non-OVX and OVX. It is concluded that HA and SCP granules result in comparable bone formation in trabecular bone defects. As judged by gene expression and histological analyses, the two materials induced different inflammatory and bone remodelling responses. The modulatory effects are associated with differences in the spatial distribution of the newly formed bone.
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| 11. |
- Nilsson, Per H., 1980-
(författare)
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Interactions between platelets and complement with implications for the regulation at surfaces
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Disturbances of host integrity have the potential to evoke activation of innate immunologic and hemostatic protection mechanisms in blood. Irrespective of whether the activating stimulus is typically immunogenic or thrombotic, it will generally affect both the complement system and platelets to a certain degree. The theme of this thesis is complement and platelet activity, which is intersected in all five included papers. The initial aim was to study the responses and mechanisms of the complement cascade in relation to platelet activation. The secondary aim was to use an applied approach to regulate platelets and complement on model biomaterial and cell surfaces. Complement activation was found in the fluid phase in response to platelet activation in whole blood. The mechanism was traced to platelet release of stored chondroitin sulfate-A (CS-A) and classical pathway activation via C1q. C3 was detected at the platelet surface, though its binding was independent of complement activation. The inhibitors factor H and C4-binding protein (C4BP) were detected on activated platelets, and their binding was partly dependent on surface-exposed CS-A. Collectively, these results showed that platelet activation induces inflammatory complement activation in the fluid phase. CS-A was shown to be a central molecule in the complement-modulatory functions of platelets by its interaction with C1q, C4BP, and factor H.Platelet activation and surface adherence were successfully attenuated by conjugating an ADP-degrading apyrase on a model biomaterial. Only minor complement regulation was seen, and was therefore targeted specifically on surfaces and cells by co-immobilizing a factor H-binding peptide together with the apyrase. This combined approach led to a synchronized inhibition of both platelet and complement activation at the interface of biomaterials/xenogeneic cells and blood.In conclusion, here presents a novel crosstalk-mechanism for activation of complement when triggering platelets, which highlights the importance of regulating both complement and platelets to lower inflammatory events. In addition, a strategy to enhance the biocompatibility of biomaterials and cells by simultaneously targeting ADP-dependent platelet activation and the alternative complement C3-convertase is proposed.
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| 12. |
- Borde, Annika, 1979
(författare)
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Design of solid dosage forms for mucosal vaccination - Investigations on the influence of excipients on product performance
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Most vaccines today are liquid formulations for parental administration. However, there are several drawbacks connected to these vaccines. Since injectable vaccines only induce systemic antibody responses, they are not effective against the various pathogens that affect mucosal surfaces with poor permeability for serum-derived antibodies, e.g. the small intestine. Further disadvantages of liquid injectable vaccines are the need for medical personnel for the administration, cold chain requirements and large packaging sizes, which all are especially negative factors in developing countries. Solid and preferably mucoadhesive vaccine formulations that are administered via mucosal surfaces would offer a good alternative to many of these problems. The aim of this thesis was therefore to study the influence of excipients in the design of such formulations regarding i) formulation-related properties (mucoadhesion and antigen release) and ii) antigen-functionality preservation during freeze-dying.Mechanistic and immunological investigations using mucoadhesive hydrophilic matrix tablets as potential formulations for sublingual immunization were performed. The effect of osmotic pressure differences on the adhesiveness of hydrophilic swelling matrix tablets was investigated and it was found that a decrease in the osmotic pressure difference resulted in a decrease in the adhesive force, i.e. the force required to detach the tablet from a wet surface. Release of the model antigen ovalbumin from hydrophilic matrix tablets and a fast releasing formulation was characterized. The Bradford Assay used for the protein quantification was found to be disturbed by the hydrophilic polymer Carbopol and a correction method was set up. Sublingual immunizations in BALB/c mice indicated a poor potential of all ER tablets to evoke intestinal immune responses, whereas an immediate release resulted in high antibody titres. Thus it was concluded that the latter formulation type should be preferred in sublingual immunization. In the second part of the thesis the stabilizing potential of different excipients during freeze-drying was tested on killed whole-cell Vibrio cholerae bacteria as a model vaccine for pathogens causing mucosal infections. Sucrose showed great potential to avoid bacterial aggregation, preserve important antigen structures and to maintain the immunogenicity of the bacteria.Hopefully, the presented findings are a help and inspiration for formulators and immunologists to develop mucosal vaccine formulations so that diseases for which today no vaccines exist can be prevented in all parts of the world.
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| 13. |
- Cardemil, Carina
(författare)
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Effects of antiresorptive agents on inflammation and bone regeneration in different osseous sites - experimental and clinical studies
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The biological mechanisms involved in bone regeneration in osteoporotic bone and the effect of antiresorptive drugs in relation to surgically inserted biomaterials are not fully understood. Improved osseointegration of titanium implants but also adverse effects of antiresorptive therapies, such as osteonecrotic jaw have been described in the literature. The aims of this research project were, firstly, to investigate and to understand the biological events determining bone regeneration and implant integration, after administration of antiresorptive agents; secondly, to determine the cellular and molecular patterns of bone regeneration at implants and synthetic bone substitutes under osteoporotic conditions and, thirdly, to determine how different skeletal sites are affected. The present research included a study of jawbone morphology and gene expression in patients treated with systemic bisphosphonates. When compared to controls, higher gene expression levels of IL-1β was observed in bisphosphonate treated patients with osteonecrosis while bisphosphonate treated patients without necrosis showed lower expression levels of caspase 8, an apoptosis marker involved in the immune response. In ovariectomised rats, zoledronic acid resulted in site-specific differences in the rate of osseointegration and also of gene expression involved in bone healing and regeneration. Strontium-doped calcium phosphate inserted in the rat femur induced lower expression of osteoclastic markers compared to hydroxyapatite and higher bone formation in the periphery of the defects. Whereas major structural changes were demonstrated in the long bones of the ovariectomised rat, less structural alterations were shown in the mandible. However, ovariectomy resulted in lower expression of genes coding for bone formation and angiogenesis in the mandible. In conclusion, the present study shows that the mandible is differently affected by experimentally induced estrogen deficiency than the long bones. Bisphosphonates, administered systemically to estrogen deficient animals, impair osseointegration in the mandible, at least partly related to a downregulation of genes important for the osteogenic process. These observations may have implications for understanding the mechanisms involved in the deranged bone healing observed in the jawbone of bisphosphonate treated patients.
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| 14. |
- Kaitainen, Salla, et al.
(författare)
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TiO2 coating promotes human mesenchymal stem cell proliferation without the loss of their capacity for chondrogenic differentiation
- 2013
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Ingår i: Biofabrication. - : Institute of Physics (IOP). - 1758-5090 .- 1758-5082. ; 5:2, s. 025009-
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Tidskriftsartikel (refereegranskat)abstract
- Human mesenchymal stem cells (hMSCs) are used in applications, which may require a large amount of cells; therefore, efficient expansion of the cells is desired. We studied whether TiO2 coating on plastic cell culture dishes could promote proliferation of hMSCs without adverse effects in chondrogenic differentiation. TiO2-films were deposited on polystyrene dishes and glass coverslips using an ultrashort pulsed laser deposition technique. Human MSCs from three donors were expanded on them until 95% confluence, and the cells were evaluated by morphology, immunocytochemistry and quantitative RT-PCR (qRT-PCR). The chondrogenic differentiation in pellets was performed after cultivation on TiO2-coated dishes. Chondrogenesis was evaluated by histological staining of proteoglycans and type II collagen, and qRT-PCR. Human MSC-associated markers STRO-1, CD44, CD90 and CD146 did not change after expansion on TiO2-coated coverslips. However, the cell number after a 48h-culture period was significantly higher on TiO2-coated culture dishes. Importantly, TiO2 coating caused no significant differences in the proteoglycan and type II collagen staining of the pellets, or the expression of chondrocyte-specific genes in the chondrogenesis assay. Thus, the proliferation of hMSCs could be significantly increased when cultured on TiO2-coated dishes without weakening their chondrogenic differentiation capacity. The transparency of TiO2-films allows easy monitoring of the cell growth and morphology under a phase-contrast microscope.
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| 15. |
- Skedung, Lisa, et al.
(författare)
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Feeling small : Exploring the Tactile Perception Limits
- 2013
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 3, s. 2617-
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Tidskriftsartikel (refereegranskat)abstract
- The human finger is exquisitely sensitive in perceiving different materials, but the question remains as to what length scales are capable of being distinguished in active touch. We combine material science with psychophysics to manufacture and haptically explore a series of topographically patterned surfaces of controlled wavelength, but identical chemistry. Strain-induced surface wrinkling and subsequent templating produced 16 surfaces with wrinkle wavelengths ranging from 300 nm to 90 mu m and amplitudes between 7 nm and 4.5 mu m. Perceived similarities of these surfaces (and two blanks) were pairwise scaled by participants, and interdistances among all stimuli were determined by individual differences scaling (INDSCAL). The tactile space thus generated and its two perceptual dimensions were directly linked to surface physical properties - the finger friction coefficient and the wrinkle wavelength. Finally, the lowest amplitude of the wrinkles so distinguished was approximately 10 nm, demonstrating that human tactile discrimination extends to the nanoscale.
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| 21. |
- Willander, Hanna, et al.
(författare)
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BRICHOS Domains Efficiently Delay Fibrillation of Amyloid beta-Peptide
- 2012
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 287:37, s. 31608-31617
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Tidskriftsartikel (refereegranskat)abstract
- Amyloid diseases such as Alzheimer, Parkinson, and prion diseases are associated with a specific form of protein mis-folding and aggregation into oligomers and fibrils rich in beta-sheet structure. The BRICHOS domain consisting of similar to 100 residues is found in membrane proteins associated with degenerative and proliferative disease, including lung fibrosis (surfactant protein C precursor; pro-SP-C) and familial dementia (Bri2). We find that recombinant BRICHOS domains from Bri2 and pro-SP-C prevent fibril formation of amyloid beta-peptides (A beta(40) and A beta(42)) far below the stoichiometric ratio. Kinetic experiments show that a main effect of BRICHOS is to prolong the lag time in a concentration-dependent, quantitative, and reproducible manner. An ongoing aggregation process is retarded if BRICHOS is added at any time during the lag phase, but it is too late to interfere at the end of the process. Results from circular dichroism and NMR spectroscopy, as well as analytical size exclusion chromatography, imply that A beta is maintained as an unstructured monomer during the extended lag phase in the presence of BRICHOS. Electron microscopy shows that although the process is delayed, typical amyloid fibrils are eventually formed also when BRICHOS is present. Structural BRICHOS models display a conserved array of tyrosine rings on a five-stranded beta-sheet, with inter-hydroxyl distances suited for hydrogen-bonding peptides in an extended beta-conformation. Our data imply that the inhibitory mechanism is reliant on BRICHOS interfering with molecular events during the lag phase.
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| 23. |
- Karlsson, Johan, 1984
(författare)
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Mesoporous Implants for Localized Controlled Drug Delivery
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The use of bone-anchored implants is today a routine treatment for patients with normal regenerative capacity. However, there is an ongoing development within implant research to improve the osseointegration of implants. Despite considerable progress, further improvements are needed to achieve a more rapid healing and to enable treatment of patients suffering from low bone amounts or poor bone quality. One approach to improve the clinical outcome of bone-anchored implants is to use drugs to promote bone tissue regeneration. When using therapeutic treatments, the delivery system is crucial to obtain high efficiency and avoid toxic side effects.The primary aim of this thesis was to investigate how mesoporous titania thin films can be used for local drug delivery to obtain enhanced osseointegration of implants. The well-defined pore structure of mesoporous materials makes them appropriate as drug delivery systems. Templates of different sizes were used, enabling the pore size to be varied from 3.4 to 7.2 nm. Moreover, the adsorption and release of different drugs from mesoporous titania were monitored using quartz crystal microbalance with dissipation. The results showed that the mesoporous titania thin films served for high drug loading and controlled release. The drug administration of the osteoporosis drug alendronate was also evaluated in vivo. The drug was radiolabelled, which enabled molecular specific detection; hence, the drug distribution into the surrounding bone and the distal diffusion could be analyzed. The results showed that most of the released drug remained within a few 100 micrometers from the implant surface. Biological evaluation demonstrated that local delivery of the osteoporosis drugs alendronate and raloxifene from mesoporous titania thin films improved the osseointegrating performance of implants and that local delivery of chemokines, for homing of stem cells, enhanced the bone tissue regeneration.Another aim was to apply novel ex vivo analytical techniques to yield knowledge about the implant-bone interface. Atom probe tomography is considered as one of the most powerful tools for microstructural characterization. This technique was used for the first time to characterize an interface between a biomedical device and tissue. The analysis provided a three-dimensional atomic reconstruction of the interface between the implant and formed bone mineral. Raman spectroscopy with mapping capability was utilized to characterize the molecular identity of the formed bone mineral at implant surfaces with and without delivery of alendronate. It was shown that it is crucial to control the drug concentration in order to promote biomineralization.The results presented and discussed in this thesis demonstrate that mesoporous titania thin films are highly suitable as a drug delivery platform for bone anchored implants. Furthermore, the novel analytical ex vivo techniques applied allowed for new insights about tissue response to biomedical implants.
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| 24. |
- Sul, Young-Taeg, 1960, et al.
(författare)
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A novel in vivo method for quantifying the interfacial biochemical bond strength of bone implants
- 2010
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Ingår i: Journal of the Royal Society Interface. - London, United Kingdom : Royal Society. - 1742-5689 .- 1742-5662. ; 7:42, s. 81-90
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Tidskriftsartikel (refereegranskat)abstract
- Quantifying the in vivo interfacial biochemical bond strength of bone implants is a biological challenge. We have developed a new and novel in vivo method to identify an interfacial biochemical bond in bone implants and to measure its bonding strength. This method, named biochemical bond measurement (BBM), involves a combination of the implant devices to measure true interfacial bond strength and surface property controls, and thus enables the contributions of mechanical interlocking and biochemical bonding to be distinguished from the measured strength values. We applied the BBM method to a rabbit model, and observed great differences in bone integration between the oxygen (control group) and magnesium (test group) plasma immersion ion-implanted titanium implants (0.046 versus 0.086 MPa, n=10, p=0.005). The biochemical bond in the test implants resulted in superior interfacial behaviour of the implants to bone: (i) close contact to approximately 2 μm thin amorphous interfacial tissue, (ii) pronounced mineralization of the interfacial tissue, (iii) rapid bone healing in contact, and (iv) strong integration to bone. The BBM method can be applied to in vivo experimental models not only to validate the presence of a biochemical bond at the bone–implant interface but also to measure the relative quantity of biochemical bond strength. The present study may provide new avenues for better understanding the role of a biochemical bond involved in the integration of bone implants.
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| 25. |
- Patra, Hirak Kumar, et al.
(författare)
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MRI-Visual Order–Disorder Micellar Nanostructures for Smart Cancer Theranostics
- 2014
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Ingår i: Advanced Healthcare Materials. - : Wiley-VCH Verlagsgesellschaft. - 2192-2640 .- 2192-2659. ; 3:4, s. 526-535
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Tidskriftsartikel (refereegranskat)abstract
- The development of MRI-visual order–disorder structures for cancer nanomedicine explores a pH-triggered mechanism for theragnosis of tumor hallmark functions. Superparamagnetic iron oxide nanoparticles (SPIONs) stabilized with amphiphilic poly(styrene)-b-poly(acrylic acid)-doxorubicin with folic acid (FA) surfacing are employed as a multi-functional approach to specifically target, diagnose, and deliver drugs via a single nanoscopic platform for cancer therapy. The functional aspects of the micellar nanocomposite is investigated in vitro using human breast SkBr3 and colon cancer HCT116 cell lines for the delivery, release, localization, and anticancer activity of the drug. For the first time, concentration-dependent T2-weighted MRI contrast for a monolayer of clustered cancer cells is shown. The pH tunable order–disorder transition of the core–shell structure induces the relative changes in MRI contrast. The outcomes elucidate the potential of this material for smart cancer theranostics by delivering non-invasive real-time diagnosis, targeted therapy, and monitoring the course and response of the action before, during, and after the treatment regimen.
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| 26. |
- Martinez Avila, Hector, 1985, et al.
(författare)
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Biocompatibility evaluation of densified bacterial nanocellulose hydrogel as an implant material for auricular cartilage regeneration
- 2014
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Ingår i: Applied Microbiology and Biotechnology. - : Springer Science and Business Media LLC. - 1432-0614 .- 0175-7598. ; 98:17, s. 7423-7435
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Tidskriftsartikel (refereegranskat)abstract
- Bacterial nanocellulose (BNC), synthesized by the bacterium Gluconacetobacter xylinus, is composed of highly hydrated fibrils (99 % water) with high mechanical strength. These exceptional material properties make BNC a novel biomaterial for many potential medical and tissue engineering applications. Recently, BNC with cellulose content of 15 % has been proposed as an implant material for auricular cartilage replacement, since it matches the mechanical requirements of human auricular cartilage. This study investigates the biocompatibility of BNC with increased cellulose content (17 %) to evaluate its response in vitro and in vivo. Cylindrical BNC structures (48 Au 20 mm) were produced, purified in a built-in house perfusion system, and compressed to increase the cellulose content in BNC hydrogels. The reduction of endotoxicity of the material was quantified by bacterial endotoxin analysis throughout the purification process. Afterward, the biocompatibility of the purified BNC hydrogels with cellulose content of 17 % was assessed in vitro and in vivo, according to standards set forth in ISO 10993. The endotoxin content in non-purified BNC (2,390 endotoxin units (EU)/ml) was reduced to 0.10 EU/ml after the purification process, level well below the endotoxin threshold set for medical devices. Furthermore, the biocompatibility tests demonstrated that densified BNC hydrogels are non-cytotoxic and cause a minimal foreign body response. In support with our previous findings, this study concludes that BNC with increased cellulose content of 17 % is a promising non-resorbable biomaterial for auricular cartilage tissue engineering, due to its similarity with auricular cartilage in terms of mechanical strength and host tissue response.
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| 27. |
- Lindahl, Carl, et al.
(författare)
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Incorporation of active ions into calcium phosphate coatings, their release behavior and mechanism.
- 2012
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Ingår i: Biomedical materials. - : IOP Publishing. - 1748-605X .- 1748-6041. ; 7:4
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Tidskriftsartikel (refereegranskat)abstract
- The dissolution and release of active ions from ion-doped apatites is currently gaining interest due to indications of a beneficial biologic response. The release of ions from apatite coatings is important because it influences the biological effect of these types of materials. In this study the ion release from three different ion-doped apatite coatings (iHA coatings), SrCaP, SiHA and FHA, has been studied. The coatings were prepared by a mineralization method based on immersion in modified PBS solutions containing additions of Sr, Si or F. The kinetics of ion release from the iHA coatings were studied in two different media with and without calcium and phosphate ions (phosphate buffer saline solution (PBS) and Tris-HCl). The amount of cumulative release of Sr, Si and F ions from the iHA coatings was SrCaP>SiHA>FHA in Tris-HCl, which could be also be related to the solubility for these iHA coatings. According to analysis using the Korsmeyer-Peppas model, the release of ions from the coatings was in most cases controlled by a combination of Fickian diffusion and dissolution of the coatings. The morphologies of the iHA coatings were not markedly changed after immersion in Tris-HCl. In the phosphate buffer solution, there was a concurrent redeposition of new apatite crystals on the surface of all of the iHA coatings, which means there were both a dissolution and a remineralization process acting, ultimately controlling the ion release rate.
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| 28. |
- Hulander, Mats, et al.
(författare)
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Gradients in surface nanotopography used to study platelet adhesion and activation
- 2013
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Ingår i: Colloids and Surfaces B-Biointerfaces. - : Elsevier BV. - 0927-7765 .- 1873-4367. ; 110, s. 261-269
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Tidskriftsartikel (refereegranskat)abstract
- Gradients in surface nanotopography were prepared by adsorbing gold nanoparticles on smooth gold substrates using diffusion technique. Following a sintering procedure the particle binding chemistry was removed, and integration of the particles into the underlying gold substrate was achieved, leaving a nanostructured surface with uniform surface chemistry. After pre-adsorption of human fibrinogen, the effect of surface nanotopography on platelets was studied. The use of a gradient in nanotopography allowed for platelet adhesion and activation to be studied as a function of nanoparticle coverage on one single substrate. A peak in platelet adhesion was found at 23% nanoparticle surface coverage. The highest number of activated platelets was found on the smooth control part of the surface, and did not coincide with the number of adhered platelets. Activation correlated inversely with particle coverage, hence the lowest fraction of activated platelets was found at high particle coverage. Hydrophobization of the gradient surface lowered the total number of adhering cells, but not the ratio of activated cells. Little or no effect was seen on gradients with 36 nm particles, suggesting the existence of a lower limit for sensing of surface nano-roughness in platelets. These results demonstrate that parameters such as ratio between size and inter-particle distance can be more relevant for cell response than wettability on nanostructured surfaces. The minor effect of hydrophobicity, the generally reduced activation on nanostructured surfaces and the presence of a cut-off in activation of human platelets as a function of nanoparticle size could have implications for the design of future blood-contacting biomaterials.
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| 29. |
- Berts, Ida, et al.
(författare)
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Polymeric Smart Coating Strategy for Titanium Implants
- 2014
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Ingår i: Advanced Engineering Materials. - : Wiley. - 1438-1656 .- 1527-2648. ; 16:11, s. 1340-1350
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Tidskriftsartikel (refereegranskat)abstract
- Hyaluronan based hydrogel coatings can mimic extracellular matrix components and incorporate growth factors that can be released during a progressive degradation while new tissue regenerates. This paper describes a structural characterization of a hydrogel coating made of modified hyaluronan polymers and how these coatings interact with bone morphogenetic protein-2 (BMP-2). Quartz crystal microbalance and neutron reflectivity measurements were used for in-situ, real-time measurements of the adsorption properties of polymers and proteins on smooth titanium oxide surfaces that mimic implant products in orthopedics. The adsorption of BMP-2 on a bare titanium oxide surface is compared to that on titanium oxide coated with different chemically modified hyaluronan, the most important being hyaluronan with bisphosphonate groups (HA-BP). The subsequent release of the BMP-2 from these hydrogel coatings could be triggered by calcium ions. The amount of adsorbed protein on the surfaces as well as the amount of released protein both depend on the type of hyaluronan coating. We conclude that HA-BP coated titanium oxide surfaces provide an excellent material for growth factor delivery in-vivo.
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| 30. |
- Jansson, Anna, 1985
(författare)
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Development of Novel In Situ Microscopy Techniques for the Study of Water Interaction with Soft Materials
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The transport of water in soft materials can occur in liquid or gas phase and is highly dependent on the material microstructure and the structure dynamics. Understanding these relationships is the basis for the development of predictive models that can aid the design of new and improved functional materials. The environmental scanning electron microscope (ESEM) enables the visualisation of the effects of hydration or dehydration on a specimen down to the nanometre scale, facilitating the understanding of the structure-property relationships. However, the full potential of the ESEM has not yet been explored, especially when it comes to the transport of water in materials. The aim of this work was to develop new ESEM-based methods that enable the in situ study of water interaction with soft materials in a controlled manner. We designed a sample stage that uses a manipulator to bring the specimen in contact with a water reservoir in the ESEM, rendering the point of contact between water and specimen available for visual studies. In addition, coupled with a piezoresistive atomic force microscopy (AFM) sensor, the setup enables the local measurement of displacements in the nanometre range with millisecond temporal resolution through force spectroscopy. Thus, it provides a sensitive probe for swelling, which is an important effect of the water interaction for many soft materials. The potential of the developed methods has been demonstrated on three different materials systems and geometries.The absorption and transport of liquid water in individual cellulose fibres were imaged for the first time. The volumes of absorbed droplets were typically in the range of 0.02 nL to 0.2 nL and the rate of absorption varied between different fibres. The method was also applied to phase-separated polymer films intended as controlled-release coatings in oral pharmaceutical formulations and enabled the first studies of the water interaction in the initial stage of wetting. Simultaneous probing of the microstructure and the local water transport properties of the films provided previously inaccessible information about the structure-transport relationships and the microstructural evolution caused by the water interaction. In addition, measurements of the time-dependent osmotic swelling of yeast cells in the ESEM were demonstrated with a high spatial and temporal resolution. This type of measurement is valuable for the understanding of the water transport properties of cell membranes. The versatility of the setup allows the technique to be applied to a wide range of different materials systems and geometries where the interaction with water is of interest.
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| 31. |
- Ubhayasekera, Sarojini Kumari, et al.
(författare)
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Effect of Feed Fat By-Products with Trans Fatty Acids and Heated Oil on Cholesterol and Oxycholesterols in Chicken
- 2010
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Ingår i: Journal of the American Oil Chemists' Society. - : Wiley. - 0003-021X .- 1558-9331. ; 87, s. 173-184
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Tidskriftsartikel (refereegranskat)abstract
- Chicken is the most widely consumed meat all over the world due to chickens being easy to rear, their fast growth rate and the meat having good nutritional characteristics. The main objective of this paper was to study the effects of dietary fatty by-products in low, medium and high levels of oxidized lipids and trans fatty acids (TFAs) on the contents of cholesterol and oxycholesterols in meat, liver, and plasma of chickens. A palm fatty acid distillate, before and after hydrogenation, and a sunflower-olive oil blend (70/30, v/v) before and after use in a commercial frying process were used in feeding trials after adding 6% of the fats to the feeds. Highly oxidized lipid and TFA feeds significantly increased the contents of cholesterol and oxycholesterols in all tissues of chicken (0.01 < p a parts per thousand currency sign 0.05). The contents of oxycholesterols in chicken meat, liver and plasma obtained from TFA feeding trials varied between 17 and 48 mu g/100 g in meat, 19-42 mu g/100 g in liver and 105-126 mu g/dL in plasma. In contrast, in the oxidized lipid feeding trials, oxycholesterols varied between 13 and 75 mu g/100 g in meat, 30-58 mu g/100 g in liver and 66-209 mu g/dL in plasma. Meat from chickens fed with feeds containing high levels of TFAs or oxidized lipids may contribute to higher ingestion of cholesterol and oxycholesterols by humans.
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| 32. |
- Islam, Mohammad Mirazul, et al.
(författare)
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Fabrication of a human recombinant collagen-based corneal substitute using carbodiimide chemistry
- 2013
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Ingår i: Methods in Molecular Biology. - Totowa, NJ : Humana Press. - 1064-3745 .- 1940-6029. - 9781627034319 ; 1014, s. 157-164
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Tidskriftsartikel (refereegranskat)abstract
- Human recombinant collagen can be cross-linked with a variety of chemical cross-linking agents. Cross-linking methods can be tuned to confer collagen-based scaffolds with specific physical properties, improved antigenicity and thermal stability without impeding the ability of the material to integrate into the surrounding tissue and to promote regeneration. Here, we describe a method to cross-link human recombinant collagen using a water soluble carbodiimide. Carbodiimides are referred to as zero-length cross-linking agents as they are not incorporated into the final cross-link and thus pose minimal risk with respect to cytotoxicity. The resulting collagen-based scaffold possesses properties comparable to that of the human cornea and is thus suitable for use as a corneal substitute.
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| 33. |
- Mladenović, Živko, et al.
(författare)
-
Soluble silica inhibits osteoclast formation and bone resorption in vitro
- 2014
-
Ingår i: Acta Biomaterialia. - : Elsevier. - 1742-7061 .- 1878-7568. ; 10:1, s. 406-418
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Tidskriftsartikel (refereegranskat)abstract
- Several studies have suggested that silicon (Si) may be essential for normal development of connective tissue and the skeleton. Positive effects of Si from the diet as well as from Si-containing biomaterials, such as Bioactive glass 45S5 (BG), have been demonstrated. Studies have reported that Si stimulates osteoblast proliferation and differentiation. However, effects of Si on osteoclasts have not been directly addressed earlier. The purpose of the present in vitro study was to clarify if Si has regulatory effects on osteoclasts formation and bone resorption. Effects of BG, BG dissolution extracts and Si containing cell culture medium were investigated in a mouse calvarial bone resorption assay and osteoclast formation assays (mouse bone marrow cultures and RAW264.7 cell cultures). We conclude from our results that Si causes significant inhibition of osteoclast phenotypic gene expressions, osteoclast formation and bone resorption in vitro. In conclusion, the present study suggests that Si has a dual nature in bone metabolism with stimulatory effects on osteoblasts and inhibitory effects on osteoclasts. This suggested property of Si might be interesting to further explore in future biomaterials for treatments of bone defects in patients.
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| 34. |
- Mohl, Melinda, et al.
(författare)
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Titania nanofibers in gypsum composites : an antibacterial and cytotoxicology study
- 2014
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Ingår i: Journal of Material Chemistry B. - : Royal Society of Chemistry. - 2050-750X .- 2050-7518. ; 2:10, s. 1307-1316
-
Tidskriftsartikel (refereegranskat)abstract
- Further developments of antibacterial coatings based on photocatalytic nanomaterials could be a promising route towards potential environmentally friendly applications in households, public buildings and health care facilities. Hereby we describe a simple chemical approach to synthesize photocatalytic nanomaterial-embedded coatings using gypsum as a binder. Various types of TiO2 nanofiber-based photocatalytic materials (nitrogen-doped and/or palladium nanoparticle decorated) and their composites with gypsum were characterized by means of scanning (SEM) and transmission (TEM) electron microscopy as well as electron and X-ray diffraction (XRD) and energy-dispersive X-ray spectroscopy (EDX) techniques. These gypsum-based composites can be directly applied as commercially available paints on indoor walls. Herein we report that surfaces coated with photocatalytic composites exhibit excellent antimicrobial properties by killing both methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA) under blue light. In the case of MSSA cells, the palladium nanoparticle-decorated and nitrogen-doped TiO2 composites demonstrated the highest antimicrobial activity. For the MRSA strain even pure gypsum samples were proven to be efficient in eradicating Gram-positive human pathogens. The cytotoxicity of freestanding TiO2 nanofibers was revealed by analyzing the viability of HeLa cells using MTT and fluorescent cell assays.
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| 35. |
- López, Alejandro
(författare)
-
Injectable Biomaterials for Spinal Applications
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The use of injectable biomaterials is growing as the demands for minimally invasive procedures, and more easily applicable implants become higher, but their availability is still limited due to the difficulties associated to their design.Each year, more than 700,000 vertebral compression fractures (VCF’s) are reported in the US and 500,000 VCF’s in Europe due to primary osteoporosis only. VCF’s can compromise the delicacy of the spinal canal and also cause back pain, which affects the patient’s quality of life. Vertebroplasty was developed in the 80’s, and has proven to be a safe minimally invasive procedure that can, quickly and sustainably, relieve the pain in patients experiencing VCF’s. However, biomaterials for vertebroplasty still have limitations. For instance, ceramic bone cements are difficult to distinguish from the bone using X-ray techniques. On the other hand, acrylic bone cements may cause adjacent vertebral fractures (AVF’s). Large clinical studies have indicated that 12 to 20% vertebroplasty recipients developed subsequent vertebral fractures, and that 41 to 67% of these, were AVF’s. This may be attributed to the load shifting and increased pressure on the adjacent endplates reached after vertebroplasty with stiff cements.The primary aim of this thesis was to develop better injectable biomaterials for spinal applications, particularly, bone cements for vertebroplasty. Water-soluble radiopacifiers were first investigated to enhance the radiopacity of resorbable ceramic cements. Additionally, different strategies to produce materials that mechanically comply with the surrounding tissues (low-modulus bone cements) were investigated. When a suitable low-modulus cement was produced, its performance was evaluated in both bovine bone, and human vertebra ex vivo models.In summary, strontium halides showed potential as water-soluble radiocontrast agents and could be used in resorbable calcium phosphates and other types of resorbable biomaterials. Conversely, linoleic acid-modified (low-modulus) cements appeared to be a promising alternative to currently available high-modulus cements. It was also shown that the influence of the cement properties on the strength and stiffness of a single vertebra depend upon the initial bone volume fraction, and that at low bone volume fractions, the initial mechanical properties of the vertebroplasty cement become more relevant. Finally, it was shown that vertebroplasty with low-modulus cements is biomechanically safe, and could become a recommended minimally invasive therapy in selected cases, especially for patients suffering from vertebral compression fractures due to osteoporosis.
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| 36. |
- Thorfve, Anna, 1982, et al.
(författare)
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Hydroxyapatite coating affects the Wnt signaling pathway during peri-implant healing in vivo
- 2014
-
Ingår i: Acta Biomaterialia. - : Elsevier BV. - 1742-7061 .- 1878-7568. ; 10:3, s. 1451-1462
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Tidskriftsartikel (refereegranskat)abstract
- Owing to its bio- and osteoconductivity, hydroxyapatite (HA) is a widely used implant material, but its osteogenic properties are only partly evaluated in vitro and in vivo. The present study focused on bone healing adjacent to HA-coated titanium (Ti) implants, with or without incorporated lithium ions (Li+). Special attention was given to the Wnt signaling pathway. The implants were inserted into rat tibia for 7 or 28days and analyzed ex vivo, mainly by histomorphometry and quantitative real-time polymerase chain reaction. HA-coated implants showed, irrespective of Li+ content, bone-implant contact (BIC) and removal torque significantly higher than those of reference Ti. Further, the expressions of OCN, CTSK, COL1A1, LRP5/6 and WISP1 were significantly higher in implant-adherent cells of HA-coated implants, with or without Li+. Significantly higher β-catenin expression and significantly lower COL2A1 expression were observed in peri-implant bone cells from HA with 14ngcm-2 released Li+. Interestingly, Ti implants showed a significantly larger bone area in the threads than HA with 39ngcm-2 released Li+, but had a lower BIC than any HA-coated implant. This study shows that HA, with or without Li+ is a strong activator of the Wnt signaling pathway, and may to some degree explain its high bone induction capacity.
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| 37. |
- Koptyug, Andrey, 1956-, et al.
(författare)
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Electron Beam Melting : Moving from Macro- to Micro- and Nanoscale
- 2012
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Ingår i: Materials Science Forum. - Switzerland : Trans Tech Publications Inc.. ; , s. 532-537
-
Konferensbidrag (refereegranskat)abstract
- This paper presents some results achieved in the biomedical applications of the EBM® technology, and describes the resolved and unresolved challenges presented by modern medical implant manufacturing. In particular it outlines the issues related to the cellular structure design and metal surface modification. Moving to precision control of the metal surface at a microand sub-micrometer scale is a serious challenge to the EBM® processing, because it uses the powder with average grain size of about 0.04 to 0.1 mm. Though manufacturing of components with solidmesh geometry and porous surfaces using EBM® is quite possible, post- processing (for example chemical or electrochemical) is needed to achieve desired control of the surface at smaller scales to realize full potential of the technology for biomedical applications.
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| 38. |
- Heiland, Vincent M., et al.
(författare)
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Identification of carotid plaque tissue properties using an experimental-numerical approach
- 2013
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Ingår i: Journal of The Mechanical Behavior of Biomedical Materials. - : Elsevier BV. - 1751-6161 .- 1878-0180. ; 27, s. 226-238
-
Tidskriftsartikel (refereegranskat)abstract
- A biomechanical stress analysis could help to identify carotid plaques that are vulnerable to rupture, and hence reduce the risk of thrombotic strokes. Mechanical stress predictions critically depend on the plaque's constitutive properties, and the present study introduces a concept to derive viscoelastic parameters through an experimental-numerical approach. Carotid plaques were harvested from two patients during carotid endarterectomy (CEA), and, in total, nine test specimens were investigated. A novel in-vitro mechanical testing protocol, which allows for dynamic testing, keeping the carotid plaque components together, was introduced. Macroscopic pictures overlaid by histological stains allowed for the segmentation of plaque tissues, in order to develop high-fidelity and low-fidelity Finite Element Method (FEM) models of the test specimens. The FEM models together with load-displacement data from the mechanical testing were used to extract constitutive parameters through inverse parameter estimation. The applied inverse parameter estimation runs in stages, first addressing the hyperelastic parameters then the viscoelastic ones. Load-displacement curves from the mechanical testing showed strain stiffening and viscoelasticity, as is expected for both normal and diseased carotid tissue. The estimated constitutive properties of plaque tissue were comparable to previously reported studies, Due to the highly non-linear elasticity of vascular tissue, the applied parameter estimation approach is, as with many similar approaches, sensitive to the initial guess of the parameters.
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| 39. |
- Fink, Helen, 1978, et al.
(författare)
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Bacterial cellulose modified with xyloglucan bearing the adhesion peptide RGD promotes endothelial cell adhesion and metabolism--a promising modification for vascular grafts.
- 2011
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Ingår i: Journal of tissue engineering and regenerative medicine. - : Hindawi Limited. - 1932-7005 .- 1932-6254. ; 5:6, s. 454-63
-
Tidskriftsartikel (refereegranskat)abstract
- Today, biomaterials such as polytetrafluorethylene (ePTFE) are used clinically as prosthetic grafts for vascular surgery of large vessels (>5 mm). In small diameter vessels, however, their performance is poor due to early thrombosis. Bacterial-derived cellulose (BC) is a new promising material as a replacement for blood vessels. This material is highly biocompatible in vivo but shows poor cell adhesion. In the native blood vessel, the endothelium creates a smooth non-thrombogenic surface. In order to sustain cell adhesion, BC has to be modified. With a novel xyloglucan (XG) glycoconjugate method, it is possible to introduce the cell adhesion peptide RGD (Arg-Gly-Asp) onto bacterial cellulose. The advantage of the XG-technique is that it is an easy one-step procedure carried out in water and it does not weaken or alter the fiber structure of the hydrogel. In this study, BC was modified with XG and XGRGD to asses primary human vascular endothelial cell adhesion, proliferation, and metabolism as compared with unmodified BC. This XG-RGD-modification significantly increased cell adhesion and the metabolism of seeded primary endothelial cells as compared with unmodified BC whereas the proliferation rate was affected only to some extent. The introduction of an RGD-peptide to the BC surface further resulted in enhanced cell spreading with more pronounced stress fiber formation and mature phenotype. This makes BC together with the XG-method a promising material for synthetic grafts in vascular surgery and cardiovascular research.
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| 40. |
- Olofsson, Johanna, 1981-, et al.
(författare)
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Evaluation of silicon nitride as a wear resistant and resorbable alternative for total joint replacement
- 2012
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Ingår i: Biomatter. - : Landes Bioscience. - 2159-2527 .- 2159-2535. ; 2:2, s. 94-102
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Tidskriftsartikel (refereegranskat)abstract
- Many of the failures of total joint replacements are related to tribology, i.e., wear of the cup, head and liner. Accumulation of wear particles at the implants can be linked to osteolysis which leads to bone loss and in the end aseptic implant loosening. Therefore it is highly desirable to reduce the generation of wear particles from the implant surfaces.Silicon nitride (Si3N4) has shown to be biocompatible and have a low wear rate when sliding against itself and is therefore a good candidate as a hip joint material. Furthermore, wear particles of Si3N4 are predicted to slowly dissolve in polar liquids and they therefore have the potential to be resorbed in vivo, potentially reducing the risk for aseptic loosening.In this study, it was shown that α-Si3N4-powder dissolves in PBS. Adsorption of blood plasma indicated a good acceptance of Si3N4 in the body with relatively low immune response. Si3N4 sliding against Si3N4showed low wear rates both in bovine serum and PBS compared with the other tested wear couples. Tribofilms were built up on the Si3N4 surfaces both in PBS and in bovine serum, controlling the friction and wear characteristics.
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| 41. |
- Dånmark, Staffan, et al.
(författare)
-
Integrin-mediated adhesion of human mesenchymal stem cells to extracellular matrix proteins adsorbed to polymer surfaces
- 2012
-
Ingår i: Biomedical Materials. - : IOP Publishing. - 1748-6041 .- 1748-605X. ; 7:3, s. 035011-
-
Tidskriftsartikel (refereegranskat)abstract
- In vitro, degradable aliphatic polyesters are widely used as cell carriers for bone tissue engineering, despite their lack of biological cues. Their biological active surface is rather determined by an adsorbed layer of proteins from the surrounding media. Initial cell fate, including adhesion and proliferation, which are key properties for efficient cell carriers, is determined by the adsorbed layer of proteins. Herein we have investigated the ability of human bone marrow derived stem cells (hBMSC) to adhere to extracellular matrix (ECM) proteins, including fibronectin and vitronectin which are present in plasma and serum. hBMSC expressed integrins for collagens, laminins, fibronectin and vitronectin. Accordingly, hBMSC strongly adhered to these purified ECM proteins by using the corresponding integrins. Although purified fibronectin and vitronectin adsorbed to aliphatic polyesters to a lower extent than to cell culture polystyrene, these low levels were sufficient to mediate adhesion of hBMSC. It was found that plasma- and serum-coated polystyrene adsorbed significant levels of both fibronectin and vitronectin, and fibronectin was identified as the major adhesive component of plasma for hBMSC; however, aliphatic polyesters adsorbed minimal levels of fibronectin under similar conditions resulting in impaired cell adhesion. Altogether, the results suggest that the efficiency of aliphatic polyesters cell carriers could be improved by increasing their ability to adsorb fibronectin.
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| 42. |
- Löberg, Johanna, 1981, et al.
(författare)
-
Electronic properties of anodized TiO2 electrodes and the effect on the in-vitro response
- 2014
-
Ingår i: Journal of Biomedical Materials Research. Part B - Applied biomaterials. - : Wiley. - 1552-4973 .- 1552-4981. ; 102:4, s. 826-839
-
Tidskriftsartikel (refereegranskat)abstract
- For dental implants, improved osseointegration is obtained by modifying the surface roughness as well as oxide morphology and composition. A combination of different effects contributes to enhanced performance, but with surface roughness as the dominant factor. In order to single out the effect of oxide conductivity on biological response, oxide films with similar thickness and surface roughness but different electronic properties were formed using galvanostatic anodization. Three different current densities were used, 2.4, 4.8 and 11.9 mAcm-2, which resulted in growth rates ranging from 0.2 to 2.5 V/s. The electronic properties were evaluated using cyclic voltammetry and impedance spectroscopy, while the biological response was studied by cell activity and apatite formation. The number of charge carrier in the oxide film close to the oxide/solution interface decreased from 5.810-19 to 3.210-19 cm-2 with increasing growth rate, i.e. the conductivity decreased correspondingly. Cell response of the different surfaces was tested in-vitro using human osteoblast-like cells (MG-63). The results clearly show decreased osteoblast proliferation and adhesion but higher mineralisation activity for the oxide with lower conductivity at the oxide/solution interface. The apatite-forming ability was examined by immersion in simulated body fluid. At short times the apatite coverage was 26% for the anodized surfaces, significantly larger than for the reference with only 3% coverage. After one week of immersion the apatite coverage ranged from 73% to 56% and a slight differentiation between the anodized surfaces was obtained with less apatite formation on the surface with lower conductivity, in line with the cell culture results.
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| 43. |
- Löberg, Johanna, 1981, et al.
(författare)
-
Integrated Biomechanical and Topographical Surface Characterization (IBTSC).
- 2014
-
Ingår i: Applied Surface Science. - 0169-4332. ; 290, s. 215-222
-
Tidskriftsartikel (refereegranskat)abstract
- In an attempt to reduce the need for animal studies in dental implant applications, a new model has been developed which combines well-known surface characterization methods with theoretical biomechanical calculations. The model has been named Integrated Biomechanical and Topographical Surface Characterization (IBTSC), and gives a comprehensive description of the surface topography and the ability of the surface to induce retention strength with bone. IBTSC comprises determination of 3D-surface roughness parameters by using 3D-Scanning Electron Microscopy (3D-SEM) and Atomic Force Microscopy (AFM), and calculation of the ability of different surface topographies to induce retention strength in bone by using the Local model. Inherent in this integrated approach is the use of a length scale analysis, which makes it possible to separate different size levels of surface features. The IBTSC concept is tested on surfaces with different level of hierarchy, induced by mechanical as well as chemical treatment. Sequential treatment with oxalic and hydrofluoric acid results in precipitated nano-sized features that increase the surface roughness and the surface slope on the sub-micro and nano levels. This surface shows the highest calculated shear strength using the Local model. The validity, robustness and applicability of the IBTSC concept are demonstrated and discussed.
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| 44. |
- Halldin, Anders, 1971, et al.
(författare)
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On a Constitutive Material Model to Capture Time Dependent Behaviour of Cortical Bone
- 2014
-
Ingår i: World Journal of Mechanics. - : Scientific Research Publishing, Inc.. - 2160-049X .- 2160-0503. ; 4:11, s. 348-361
-
Tidskriftsartikel (refereegranskat)abstract
- It is commonly known that cortical bone exhibits viscoelastic-viscoplastic behavior which affects the biomechanical response when an implant is subjected to an external load. In addition, long term effects such as creep, relaxation and remodeling affect the success of the implant over time. Constitutive material models are commonly derived from data obtained in in vitro experiments. However during function, remodeling of bone greatly affects the bone material over time. Hence it is essential to include long term in vivo effects in a constitutive model of bone. This paper proposes a constitutive material model for cortical bone incorporating viscoelasticity, viscoplasticity, creep and remodeling to predict stress-strain at various strain rates as well as the behavior of bone over time in vivo. The rheological model and its parameters explain the behavior of bone subjected to longitudinal loading. By a proper set of model parameters, for a specific cortical bone, the present model can be used for prediction of the behavior of this bone under specific loading conditions. In addition simulation with the proposed model demonstrates excellent agreement to in vitro and in vivo experimental results in the literature.
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| 45. |
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| 46. |
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| 47. |
- Unosson, Johanna, 1985-
(författare)
-
Physical Properties of Acidic Calcium Phosphate Cements
- 2014
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The gold standard for bone replacement today, autologous bone, suffers from several disadvantages, such as the increased risk of infection due to the need for two surgeries. Degradable synthetic materials with properties similar to bone, such as calcium phosphate cements, are a promising alternative. Calcium phosphate cements are suited for a limited amount of applications and improving their physical properties could extend their use into areas previously not considered possible. For example, cement with increased strength could be used as load bearing support in selected applications. The focus of this thesis is, therefore, on how the physical properties of acidic calcium phosphate cements (brushite cements) are affected by compositional variations, with the ultimate aim of making it possible to formulate brushite cements with desired properties.In this thesis a method to measure the porosity of a cement was developed. This method is advantageous over existing methods as it is easy to use, requiring no advanced equipment. A model estimating the porosity of the hardened cement from the initial chemical composition was further formulated and the accuracy affirmed. Utilization of this model allows the porosity to be optimized by calculations rather than extensive laboratory work. The effect on strength and porosity of several compositional variations were also assessed and it was found that the optimal composition to achieve a high strength was: monocalcium phosphate particles in sizes <75µm, 10 mol% excess of beta-tricalcium phosphate, 1 wt% disodium dihydrogen pyrophosphate, and 0.5 M citric acid in a liquid-to-powder ratio of 0.22 ml/g. This composition gave the highest compressive strength historically measured for this type of cement, i.e., 74.4 (±10.7) MPa. Although such a high strength may not be necessary for all applications, it allows for the use of brushite cements in new applications. Furthermore, a high strength of the bulk allows for alterations to the cement that cause a decrease in strength. One application is fast degrading materials, allowing rapid bone ingrowth. A fast degradation is obtained with a high macroporosity, which would reduce strength. The high strength composition was therefore utilized to achieve brushite cement with a high macroporosity.
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| 48. |
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| 49. |
- Yang, L., et al.
(författare)
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Biomimetic calcium phosphate coatings on recombinant spider silk fibres
- 2010
-
Ingår i: Biomedical Materials. - : Institute of Physics (IOP). - 1748-6041 .- 1748-605X. ; 5:4
-
Tidskriftsartikel (refereegranskat)abstract
- Calcium phosphate ceramic coatings, applied on surfaces of metallic and polymeric biomaterials, can improve their performance in bone repair and regeneration. Spider silk is biocompatible, strong and elastic, and hence an attractive biomaterial for applications in connective tissue repair. Recently, artificial spider silk, with mechanical and structural characteristics similar to those of native spider silk, has been produced from recombinant minispidroins. In the present study, supersaturated simulated body fluid was used to deposit calcium phosphate coatings on recombinant spider silk fibres. The mineralization process was followed in time using scanning electron microscopy equipped with an energy dispersive x-ray (EDX) detector and Raman spectroscope. Focused ion beam technology was used to produce a cross section of a coated fibre, which was further analysed by EDX. Preliminary in vitro experiments using a culture of bone marrow-derived human mesenchymal stem cells (hMSCs) on coated fibres were also performed. This study showed that recombinant spider silk fibres were successfully coated with a homogeneous and thick crystalline calcium phosphate layer. In the course of the mineralization process from modified simulated body fluid, sodium chloride crystals were first deposited on the silk surface, followed by the deposition of a calcium phosphate layer. The coated silk fibres supported the attachment and growth of hMSCs.
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| 50. |
- Nogueira, Eugenia, et al.
(författare)
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Liposome and protein based stealth nanoparticles
- 2013
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Ingår i: Faraday discussions. - : Royal Society of Chemistry (RSC). - 1359-6640 .- 1364-5498. ; 166, s. 417-429
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Tidskriftsartikel (refereegranskat)abstract
- Liposomes and protein based nanoparticles were tuned with different polymers and glycolipids to improve stealth and thus decrease their clearance by macrophages. Liposomes were coated with polyethylene glycol (PEG) and brain-tissue-derived monosialoganglioside (GM1). Bovine serum albumin (BSA) nanoparticles were produced incorporating a PEGylated surfactant (PEG-surfactant). All obtained nanoparticles were monodisperse, with sizes ranging from 80 to 120 nm, with a zeta-potential close to zero. The presented stealth strategies lead to a decrease of internalization levels by macrophages. These surface modified nanoparticles could be used for production of new drug delivery nanosystems for systemic administration (e.g. intravenous application).
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