| 1. |
- Palmquist, Anders, 1977, et al.
(författare)
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Complex geometry and integrated macro-porosity: Clinical applications of electron beam melting to fabricate bespoke bone-anchored implants
- 2023
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Ingår i: Acta Biomaterialia. - : Elsevier BV. - 1742-7061 .- 1878-7568. ; 156, s. 125-145
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Forskningsöversikt (refereegranskat)abstract
- The last decade has witnessed rapid advancements in manufacturing technologies for biomedical implants. Additive manufacturing (or 3D printing) has broken down major barriers in the way of producing complex 3D geometries. Electron beam melting (EBM) is one such 3D printing process applicable to metals and alloys. EBM offers build rates up to two orders of magnitude greater than comparable laser-based technologies and a high vacuum environment to prevent accumulation of trace elements. These features make EBM particularly advantageous for materials susceptible to spontaneous oxidation and nitrogen pick-up when exposed to air (e.g., titanium and titanium-based alloys). For skeletal reconstruction(s), anatomical mimickry and integrated macro-porous architecture to facilitate bone ingrowth are undoubtedly the key features of EBM manufactured implants. Using finite element modelling of physiological loading conditions, the design of a prosthesis may be further personalised. This review looks at the many unique clinical applications of EBM in skeletal repair and the ground-breaking innovations in prosthetic rehabilitation. From a simple acetabular cup to the fifth toe, from the hand-wrist complex to the shoulder, and from vertebral replacement to cranio-maxillofacial reconstruction, EBM has experienced it all. While sternocostal reconstructions might be rare, the repair of long bones using EBM manufactured implants is becoming exceedingly frequent. Despite the various merits, several challenges remain yet untackled. Nevertheless, with the capability to produce osseointegrating implants of any conceivable shape/size, and permissive of bone ingrowth and functional loading, EBM can pave the way for numerous fascinating and novel applications in skeletal repair, regeneration, and rehabilitation. Statement of significance: Electron beam melting (EBM) offers unparalleled possibilities in producing contaminant-free, complex and intricate geometries from alloys of biomedical interest, including Ti6Al4V and CoCr. We review the diverse range of clinical applications of EBM in skeletal repair, both as mass produced off-the-shelf implants and personalised, patient-specific prostheses. From replacing large volumes of disease-affected bone to complex, multi-material reconstructions, almost every part of the human skeleton has been replaced with an EBM manufactured analog to achieve macroscopic anatomical-mimickry. However, various questions regarding long-term performance of patient-specific implants remain unaddressed. Directions for further development include designing personalised implants and prostheses based on simulated loading conditions and accounting for trabecular bone microstructure with respect to physiological factors such as patient's age and disease status.
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| 2. |
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| 3. |
- Berglund, Fanny, et al.
(författare)
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Evidence for wastewaters as environments where mobile antibiotic resistance genes emerge
- 2023
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- The emergence and spread of mobile antibiotic resistance genes (ARGs) in pathogens have become a serious threat to global health. Still little is known about where ARGs gain mobility in the first place. Here, we aimed to collect evidence indicating where suchinitial mobilizationevents of clinically relevant ARGs may have occurred. We found that the majority of previously identified origin species did not carry the mobilizing elements that likely enabled intracellular mobility of the ARGs, suggesting a necessary interplay between different bacteria. Analyses of a broad range of metagenomes revealed that wastewaters and wastewater-impacted environments had by far the highest abundance of both origin species and corresponding mobilizing elements. Most origin species were only occasionally detected in other environments. Co-occurrence of origin species and corresponding mobilizing elements were rare in human microbiota. Our results identify wastewaters and wastewater-impacted environments as plausible arenas for the initial mobilization of resistance genes.
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| 4. |
- 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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| 5. |
- Jing, Yujia, 1985
(författare)
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Hyperthermia-responsive liposomal systems
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Abstract Sophisticated liposomal systems are emerging at an increasing rate to meet the demands for multifunctional drug carriers in chemotherapies in combined with hyperthermia. For example, liposomal drug carriers for temperature-controlled drug release under hyperthermic conditions have recently been tested in clinical trials. More advanced designs of liposomes are expected to release encapsulated contents and activate hidden surface-functions in response to heat stimulus. Towards this aim, the present thesis is focused on formulating asymmetric lipid systems that can preserve functional moieties, and reactivate the targeted function as well as release the encapsulated compounds upon local heating. The design of the asymmetric liposomal systems utilizes the heat-activated transmembrane lipid diffusion during gel to liquid-crystalline phase transitions of the lipid membranes.Rational design of advanced liposomal drug-delivery systems will require understanding of the physicochemical properties of lipid membranes under, e.g., hyperthermic conditions. Here, supported lipid membranes on planar solid surfaces were used for model studies of lipid composition yielding a gel to liquid crystalline phase-transition temperature in the range 40 – 45 °C. It was found that the liposome-to-membrane formation process is not only size-dependent but also governed by temperature. Two methods of preparing supported asymmetric lipid membranes were investigated. As a proof-of-concept, the upper leaflets were either replaced or chemically transformed by enzymatic hydrolysis. The processes were monitored using surface sensitive techniques such as quartz crystal microbalance with dissipation (QCM-D) and dual polarization interferometry (DPI). The asymmetric structures were stable at a room temperature, while lipid flip-flop was induced upon increasing of the temperature. Transmembrane lipid exchange in the asymmetric structure under hyperthermic conditions was demonstrated by detecting, through streptavidin binding, biotinylated lipids appearing at the top leaflet which were first located in the lower leaflet. The protocols developed for the supported lipid systems were adapted for the preparation of asymmetric liposomes. Biotinylated asymmetric liposomes were used as a model system to demonstrate the principle of heat-activated targeting of asymmetric liposomes to streptavidin-coated surfaces. More biologically relevant interaction was utilized to replace the biotin-streptavidin function, where asymmetric cationic liposomes were binding to anionic supported membrane immobilized surfaces upon heating. The described strategies for assembly of asymmetric supported membranes provide a guide to the development of multifunctional drug carriers. The protocols used in experiments with supported membranes were readily adapted to the preparation of asymmetric liposomes. The ongoing study tests the asymmetric liposomes in vitro, which is designed to demonstrate hyperthermia treatment can enhance accumulation of liposomes in FaDu cells, and at the same time activate release of the encapsulated components. The results of in vitro tests can be used to analyze the feasibility of utilizing the asymmetric liposomes as a platform in vivo to explore further improvement in their functions upon microwave hyperthermia.
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| 6. |
- Orru, Anna Maria, 1976, et al.
(författare)
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AHA! festival 2015
- 2015
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The AHA festival investigates the borders between art and science in a three-day event at the Chalmers University of Technology hosted by the Department of Architecture. An international festival intended to provide enlightening experiences, staging surprises, new thoughts and displaced perspectives that lead to alternative modes of thinking about the space between art and science. We invite scientists (physicists, historians, mathematicians, medical students), artists (dancers, musicians, painters, poets, chefs) and not least architects, who reside in these borderlands and wish to share their vision and work. The key intention is to celebrate both art and science as key knowledge building devices.
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| 7. |
- Peruzzi, Niccolò, et al.
(författare)
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Multimodal ex vivo methods reveal that Gd-rich corrosion byproducts remain at the implant site of biodegradable Mg-Gd screws
- 2021
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Ingår i: Acta Biomaterialia. - : Elsevier. - 1742-7061 .- 1878-7568. ; 136, s. 582-591
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Tidskriftsartikel (refereegranskat)abstract
- Extensive research is being conducted on magnesium (Mg) alloys for bone implant manufacturing, due to their biocompatibility, biodegradability and mechanical properties. Gadolinium (Gd) is among the most promising alloying elements for property control in Mg alloy implants; however, its toxicity is controversial. Investigating Gd behavior during implant corrosion is thus of utmost importance. In this study, we analyzed the degradation byproducts at the implant site of biodegradable Mg-5Gd and Mg-10Gd implants after 12 weeks healing time, using a combination of different imaging techniques: histology, energy-dispersive x-ray spectroscopy (EDX), x-ray microcomputed tomography (µCT) and neutron µCT. The main finding has been that, at the healing time in exam, the corrosion appears to have involved only the Mg component, which has been substituted by calcium and phosphorus, while the Gd remains localized at the implant site. This was observed in 2D by means of EDX maps and extended to 3D with a novel application of neutron tomography. X-ray fluorescence analysis of the main excretory organs also did not reveal any measurable accumulation of Gd, further reinforcing the conclusion that very limited or no removal at all of Gd-alloy happened during degradation.
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| 8. |
- 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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| 9. |
- Myllymaa, Katja, et al.
(författare)
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Improved adherence and spreading of Saos-2 cells on polypropylene surfaces achieved by surface texturing and carbon nitride coating.
- 2009
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Ingår i: Journal of materials science. Materials in medicine. - : Springer. - 0957-4530 .- 1573-4838. ; 20:11, s. 2337-2347
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Tidskriftsartikel (refereegranskat)abstract
- The adhesion and contact guidance of human primary osteogenic sarcoma cells (Saos-2) were characterized on smooth, microstructured (MST) and micro- and nano-structured (MNST) polypropylene (PP) and on the same samples with a silicon-doped carbon nitride (C(3)N(4)-Si) coating. Injection molding was used to pattern the PP surfaces and the coating was obtained by using ultra-short pulsed laser deposition (USPLD). Surfaces were characterized using atomic force microscopy and surface energy components were calculated according to the Owens-Wendt model. The results showed C(3)N(4)-Si coated surfaces to be significantly more hydrophilic than uncoated ones. In addition, there were 86% more cells in the smooth C(3)N(4)-Si coated PP compared to smooth uncoated PP and 551%/476% more cells with MST/MNST C(3)N(4)-Si coated PP than could be obtained with MST/MNST uncoated PP. Thus the adhesion, spreading and contact guidance of osteoblast-like cells was effectively improved by combining surface texturing and deposition of osteocompatible C(3)N(4)-Si coating.
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| 10. |
- Apelgren, Peter, et al.
(författare)
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Chondrocytes and stem cells in 3D-bioprinted structures create human cartilage in vivo.
- 2017
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 12:12
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Tidskriftsartikel (refereegranskat)abstract
- Cartilage repair and replacement is a major challenge in plastic reconstructive surgery. The development of a process capable of creating a patient-specific cartilage framework would be a major breakthrough. Here, we described methods for creating human cartilage in vivo and quantitatively assessing the proliferative capacity and cartilage-formation ability in mono- and co-cultures of human chondrocytes and human mesenchymal stem cells in a three-dimensional (3D)-bioprinted hydrogel scaffold. The 3D-bioprinted constructs (5 × 5 × 1.2 mm) were produced using nanofibrillated cellulose and alginate in combination with human chondrocytes and human mesenchymal stem cells using a 3D-extrusion bioprinter. Immediately following bioprinting, the constructs were implanted subcutaneously on the back of 48 nude mice and explanted after 30 and 60 days, respectively, for morphological and immunohistochemical examination. During explantation, the constructs were easy to handle, and the majority had retained their macroscopic grid appearance. Constructs consisting of human nasal chondrocytes showed good proliferation ability, with 17.2% of the surface areas covered with proliferating chondrocytes after 60 days. In constructs comprising a mixture of chondrocytes and stem cells, an additional proliferative effect was observed involving chondrocyte production of glycosaminoglycans and type 2 collagen. This clinically highly relevant study revealed 3D bioprinting as a promising technology for the creation of human cartilage.
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| 11. |
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| 12. |
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| 13. |
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| 14. |
- Nygren, Håkan, 1952, et al.
(författare)
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Mineralization at Titanium Surfaces is a Two-Step Process.
- 2016
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Ingår i: Journal of functional biomaterials. - : MDPI AG. - 2079-4983. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Mapping the initial reaction of implants with blood or cell culture medium is important for the understanding of the healing process in bone. In the present study, the formation of low crystalline carbonated hydroxyapatite (CHA) onto commercially pure titanium (Ti) implants from cell culture medium and blood, is described as an early event in bone healing at implants. The Ti-implants were incubated with cell culture medium (DMEM) or whole blood and the surface concentration of Ca, P and HA was analyzed by XPS, EDX and Tof-SIMS. After incubation with DMEM for 16 h and 72 h, EDX and XPS analysis showed stable levels of Ca and P on the Ti-surface. ESEM images showed an even distribution of Ca and P. Further analysis of the XPS results indicated that CHA was formed at the implants. Analysis with ToF-SIMS yielded high m.w. fragments of HA, such as Ca₂PO4 at m/z 174.9 and Ca₃PO₅ at m/z 230.8, as secondary ions at the Ti-surfaces. Analysis of implants incubated in blood for 16 h, with ToF-SIMS, showed initial formation of CHA yielding CaOH as secondary ion. The results indicate that early mineralization at Ti-surfaces is an important step in the healing of implants into bone.
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| 15. |
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| 16. |
- Andersson, Marlene, et al.
(författare)
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Biomimetic spinning of artificial spider silk from a chimeric minispidroin
- 2017
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Ingår i: Nature Chemical Biology. - : Springer Science and Business Media LLC. - 1552-4450 .- 1552-4469. ; 254
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Tidskriftsartikel (refereegranskat)abstract
- Herein we present a chimeric recombinant spider silk protein (spidroin) whose aqueous solubility equals that of native spider silk dope and a spinning device that is based solely on aqueous buffers, shear forces and lowered pH. The process recapitulates the complex molecular mechanisms that dictate native spider silk spinning and is highly efficient; spidroin from one liter of bacterial shake-flask culture is enough to spin a kilometer of the hitherto toughest as-spun artificial spider silk fiber.
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| 17. |
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| 18. |
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| 19. |
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| 20. |
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| 21. |
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| 22. |
- 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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| 23. |
- von Mentzer, Ula, 1995, et al.
(författare)
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Biomaterial Integration in the Joint: Pathological Considerations, Immunomodulation, and the Extracellular Matrix
- 2022
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Ingår i: Macromolecular Bioscience. - : Wiley. - 1616-5195 .- 1616-5187. ; 22:7
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Forskningsöversikt (refereegranskat)abstract
- Defects of articular joints are becoming an increasing societal burden due to a persistent increase in obesity and aging. For some patients suffering from cartilage erosion, joint replacement is the final option to regain proper motion and limit pain. Extensive research has been undertaken to identify novel strategies enabling earlier intervention to promote regeneration and cartilage healing. With the introduction of decellularized extracellular matrix (dECM), researchers have tapped into the potential for increased tissue regeneration by designing biomaterials with inherent biochemical and immunomodulatory signals. Compared to conventional and synthetic materials, dECM-based materials invoke a reduced foreign body response. It is therefore highly beneficial to understand the interplay of how these native tissue-based materials initiate a favorable remodeling process by the immune system. Yet, such an understanding also demands increasing considerations of the pathological environment and remodeling processes, especially for materials designed for early disease intervention. This knowledge will avoid rejection and help predict complications in conditions with inflammatory components such as arthritides. This review outlines general issues facing biomaterial integration and emphasizes the importance of tissue-derived macromolecular components in regulating essential homeostatic, immunological, and pathological processes to increase biomaterial integration for patients suffering from joint degenerative diseases.
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| 24. |
- Gullfot, Fredrika, 1967-
(författare)
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Synthesis of xyloglucan oligo- and polysaccharides with glycosynthase technology
- 2009
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Xyloglucans are polysaccharides found as storage polymers in seeds and tubers, and as cross-linking glycans in the cell wall of plants. Their structure is complex with intricate branching patterns, which contribute to the physical properties of the polysaccharide including its binding to and interaction with other glycans such as cellulose. Xyloglucan is widely used in bulk quantities in the food, textile and paper making industries. With an increasing interest in technically more advanced applications of xyloglucan, such as novel biocomposites, there is a need to understand and control the properties and interactions of xyloglucan with other compounds, to decipher the relationship between xyloglucan structure and function, and in particular the effect of different branching patterns. However, due to the structural heterogeneity of the polysaccharide as obtained from natural sources, relevant studies have not been possible to perform in practise. This fact has stimulated an interest in synthetic methods to obtain xyloglucan mimics and analogs with well-defined structure and decoration patterns. Glycosynthases are hydrolytically inactive mutant glycosidases that catalyse the formation of glycosidic linkages between glycosyl fluoride donors and glycoside acceptors. Since its first conception in 1998, the technology is emerging as a useful tool in the synthesis of large, complex polysaccharides. This thesis presents the generation and characterisation of glycosynthases based on xyloglucanase scaffolds for the synthesis of well-defined homogenous xyloglucan oligo- and polysaccharides with regular substitution patterns.
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| 25. |
- Ferrand-Drake Del Castillo, Gustav, 1990
(författare)
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Polyelectrolyte Brush Electrodes for Protein Capture and Release
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Stimuli-responsive polyelectrolyte brushes switch as a function of pH between a charged and neutral state that affects their electrostatic interactions with other charged molecules like proteins. Adjustment of the pH results in the binding of large quantities of proteins making polyelectrolyte brushes widely used as biointerfaces. However, the interaction between proteins and polyelectrolyte brushes remains poorly understood. Protein binding to brushes despite net repulsion indicates that the mechanism is determined by more than electrostatic effects. In this thesis polyelectrolyte brushes, and protein-polyelectrolyte interactions were characterized using new methods. The results show that non-electrostatic interactions play an important role in protein binding to pH-responsive polyelectrolyte brushes. Active switching of polyelectrolyte brushes requires control of the pH. However, controlled pH switching that is convenient and non-invasive has proven difficult to achieve. In this thesis electrochemistry was used to generate local pH gradients, that resulted in reversible switches of polyelectrolyte brushes, even in highly buffered liquids and in biological solutions like serum. Reversible electrochemical switching of polyelectrolyte brushes was accomplished by employing diazonium salt surface functionalization. Electrochemical switching was used to control protein-polyelectrolyte interactions to create polyelectrolyte brush electrodes that captured and released high quantities of proteins on-demand. Our method for electronic control of protein immobilization should increase the utility of pH-stimuli-responsive polymer brushes in applications such as bioanalytics, protein purification, and protein drug-delivery.
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| 26. |
- Malmberg, Per, 1974, et al.
(författare)
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Formation of hydroxyapatite on titanium implants in vivo precedes bone-formation during healing
- 2017
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Ingår i: Biointerphases. - : American Vacuum Society. - 1934-8630 .- 1559-4106. ; 12:4
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Tidskriftsartikel (refereegranskat)abstract
- The bone material interface has been an area of intense study over many decades, where studies of the healing process ranging from simple mineral deposition in vitro to actual healing in vivo have given important clues to the importance of calcium minerals in the bone/implant interface. Here, the authors use a combination of in vitro cell culture methods and in vivo implantation to study how the role of the spontaneously formed hydroxyapatite layer on Ti-implants for the in vivo-healing into the bone tissue of rat tibia. Initial experiments were made in reduced systems by incubation of TiO2 in cell culture medium and analysis by time of flight secondary ion mass spectrometry (ToF-SIMS) and energy-dispersive x-ray spectroscopy followed by subsequent exposure of human embryological stem cells analyzed by von Kossa staining and environmental scanning electron microsopy. In vivo studies of the bone-material interface was analyzed by ToF-SIMS depth profiling using both C-60(+) ions as well as a gas cluster ion source beam, Ar-1500(+) as sputter source. The low ion yield of the Ar-1500(+) for inorganics allowed the inorganic/organic interface of the implant to be studied avoiding the erosion of the inorganic materials caused by the conventional C-60(+) beam. (C) 2017 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
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| 27. |
- Asif, Sana, et al.
(författare)
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Heparinization of cell surfaces with short peptide-conjugated PEG-lipid regulates thromboinflammation in transplantation of human MSCs and hepatocytes
- 2016
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Ingår i: Acta Biomaterialia. - : Elsevier BV. - 1742-7061 .- 1878-7568. ; 35, s. 194-205
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Tidskriftsartikel (refereegranskat)abstract
- Infusion of therapeutic cells into humans is associated with immune responses, including thromboinflammation, which result in a large loss of transplanted cells\ To address these problems, heparinization of the cell surfaces was achieved by a cell-surface modification technique using polyethylene glycol conjugated phospholipid (PEG-lipid) derivatives. A short heparin-binding peptide was conjugated to the PEG-lipid for immobilization of heparin conjugates on the surface of human mesenchymal stem cells (hMSCs) and human hepatocytes. Here three kinds of heparin-binding peptides were used for immobilizing heparin conjugates and examined for the antithrombogenic effects on the cell surface. The heparinized cells were incubated in human whole blood to evaluate their hemocompatibility by measuring blood parameters such as platelet count, coagulation markers, complement markers, and Factor Xa activity. We found that one of the heparin-binding peptides did not show cytotoxicity after the immobilization with heparin conjugates. The degree of binding of the heparin conjugates on the cell surface (analyzed by flow cytometer) depended on the ratio of the active peptide to control peptide. For both human MSCs and hepatocytes in whole-blood experiments, no platelet aggregation was seen in the heparin conjugate-immobilized cell group vs. the controls (non-coated cells or control peptide). Also, the levels of thrombin-antithrombin complex (TAT), C3a, and sC5b-9 were significantly lower than those of the controls, indicating a lower activation of coagulation and complement. Factor Xa analysis indicated that the heparin conjugate was still active on the cell surface at 24 h post-coating. It is possible to immobilize heparin conjugates onto hMSC and human hepatocyte surfaces and thereby protect the cell surfaces from damaging thromboinflammation. Statement of Signigficance We present a promising approach to enhance the biocompatibility of therapeutic cells. Here we used short peptide-conjugated PEG-lipid for cell surface modification and heparin conjugates for the coating of human hepatocytes and MSCs. We screened the short peptides to find higher affinity for heparinization of cell surface and performed hemocompatibility assay of heparinized human hepatocytes and human MSCs in human whole blood. Using heparin-binding peptide with higher affinity, not only coagulation activation but also complement activation was significantly suppressed. Thus, it was possible to protect human hepatocytes and human MSCs from the attack of thromboinflammatory activation, which can contribute to the improvement graft survival. (C) 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
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| 28. |
- Dietrich, Franciele, et al.
(författare)
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Effect of storage and preconditioning of healing rat Achilles tendon on structural and mechanical properties
- 2021
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Tendon tissue storage and preconditioning are often used in biomechanical experiments and whether this generates alterations in tissue properties is essential to know. The effect of storage and preconditioning on dense connective tissues, like tendons, is fairly understood. However, healing tendons are unlike and contain a loose connective tissue. Therefore, we investigated if storage of healing tendons in the fridge or freezer changed the mechanical properties compared to fresh tendons, using a pull-to-failure or a creep test. Tissue morphology and cell viability were also evaluated. Additionally, two preconditioning levels were tested. Rats underwent Achilles tendon transection and were euthanized 12 days postoperatively. Statistical analyzes were done with one-way ANOVA or Student’s t-test. Tissue force and stress were unaltered by storage and preconditioning compared to fresh samples, while high preconditioning increased the stiffness and modulus (p ≤ 0.007). Furthermore, both storage conditions did not modify the viscoelastic properties of the healing tendon, but altered transverse area, gap length, and water content. Cell viability was reduced after freezing. In conclusion, preconditioning on healing tissues can introduce mechanical data bias when having extensive tissue strength diversity. Storage can be used before biomechanical testing if structural properties are measured on the day of testing.
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| 29. |
- Matthiesen, Isabelle, et al.
(författare)
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Continuous Monitoring Reveals Protective Effects of N‐Acetylcysteine Amide on an Isogenic Microphysiological Model of the Neurovascular Unit
- 2021
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Ingår i: Small. - : Wiley. - 1613-6810 .- 1613-6829. ; 17:32, s. 2101785-
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Tidskriftsartikel (refereegranskat)abstract
- Microphysiological systems mimic the in vivo cellular ensemble and microenvironment with the goal of providing more human-like models for biopharmaceutical research. In this study, the first such model of the blood-brain barrier (BBB-on-chip) featuring both isogenic human induced pluripotent stem cell (hiPSC)-derived cells and continuous barrier integrity monitoring with <2 min temporal resolution is reported. Its capabilities are showcased in the first microphysiological study of nitrosative stress and antioxidant prophylaxis. Relying on off-stoichiometry thiol–ene–epoxy (OSTE+) for fabrication greatly facilitates assembly and sensor integration compared to the prevalent polydimethylsiloxane devices. The integrated cell–substrate endothelial resistance monitoring allows for capturing the formation and breakdown of the BBB model, which consists of cocultured hiPSC-derived endothelial-like and astrocyte-like cells. Clear cellular disruption is observed when exposing the BBB-on-chip to the nitrosative stressor linsidomine, and the barrier permeability and barrier-protective effects of the antioxidant N-acetylcysteine amide are reported. Using metabolomic network analysis reveals further drug-induced changes consistent with prior literature regarding, e.g., cysteine and glutathione involvement. A model like this opens new possibilities for drug screening studies and personalized medicine, relying solely on isogenic human-derived cells and providing high-resolution temporal readouts that can help in pharmacodynamic studies.
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| 30. |
- Borde, Annika, 1979
(författare)
-
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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| 31. |
- Ekblad, Alf, et al.
(författare)
-
Forest soil respiration rate and d13C is regulated by recent above ground weather conditions
- 2005
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Ingår i: Oecologia. - : Springer Science and Business Media LLC. - 0029-8549 .- 1432-1939. ; 143:1, s. 136-142
-
Tidskriftsartikel (refereegranskat)abstract
- Soil respiration, a key component of the global carbon cycle, is a major source of uncertainty when estimating terrestrial carbon budgets at ecosystem and higher levels. Rates of soil and root respiration are assumed to be dependent on soil temperature and soil moisture yet these factors often barely explain half the seasonal variation in soil respiration. We here found that soil moisture (range 16.5-27.6% of dry weight) and soil temperature (range 8-17.5 degrees C) together explained 55% of the variance (cross-validated explained variance; Q2) in soil respiration rate (range 1.0-3.4 micromol C m(-2) s(-1)) in a Norway spruce (Picea abies) forest. We hypothesised that this was due to that the two components of soil respiration, root respiration and decomposition, are governed by different factors. We therefore applied PLS (partial least squares regression) multivariate modelling in which we, together with below ground temperature and soil moisture, used the recent above ground air temperature and air humidity (vapour pressure deficit, VPD) conditions as x-variables. We found that air temperature and VPD data collected 1-4 days before respiration measurements explained 86% of the seasonal variation in the rate of soil respiration. The addition of soil moisture and soil temperature to the PLS-models increased the Q2 to 93%. delta13C analysis of soil respiration supported the hypotheses that there was a fast flux of photosynthates to root respiration and a dependence on recent above ground weather conditions. Taken together, our results suggest that shoot activities the preceding 1-6 days influence, to a large degree, the rate of root and soil respiration. We propose this above ground influence on soil respiration to be proportionally largest in the middle of the growing season and in situations when there is large day-to-day shifts in the above ground weather conditions. During such conditions soil temperature may not exert the major control on root respiration.
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| 32. |
- Iseri, Emre
(författare)
-
Microfluidic Compartmentalization for Smart Materials, Medical Diagnostics and Cell Therapy
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The organisation of fluids in small compartments is ubiquitous in nature, such as in the cellular composition of all life. This work explores several engineering avenues where microscale fluid compartmentalization can bring novel material properties or novel functionality in life sciences or medicine. Here, we introduce four unique compartmentalization methods: 1) 3D fluid self-organisation in microscaffolds (FLUID3EAMS), 2) 2D microcapillary arrays on a dipstick (Digital Dipstick), 3) a sliding microfluidic platform with cross-flow (Slip-X-Chip), and 4) compartmentalization by cutting of soft solid matter (Solidify & Cut). These methods were used in a wide range of applications. Within the area of smart materials, we applied FLUID3EAMS to synthesize materials with temperature-tuneable permeability and surface energy and to establish, in a well-controlled fashion, tissue-like materials in the form of 3D droplet interface bilayer networks. Solidify & Cut was used to form soft composites with a new type of magnetic behaviour, rotation-induced ferromagnetism, that allows easy reprogramming of the magnetization of magnetopolymers. Within the area of medical diagnostics, we applied Digital Dipstick to perform rapid digital bacterial culture in a dipstick format and obtained clinically relevant diagnostic results on samples from patients with a urinary tract infection. Furthermore, Slip-X-Chip enables particle concentration and washing as new functions in sliding microfluidic platforms, which significantly expands their potential application area. Finally, within the area of cell therapy, we explored the microencapsulation of high concentrations of therapeutic cells and presented a novel technique to fabricate core-shell microcapsules by exploiting the superior material properties of spider silk membranes.
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| 33. |
- Johansson, Martin L, et al.
(författare)
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Non-invasive sampling procedure revealing the molecular events at different abutments of bone-anchored hearing systems–A prospective clinical pilot study
- 2022
-
Ingår i: Frontiers in Neuroscience. - : Frontiers Media SA. - 1662-4548 .- 1662-453X. ; 16
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: To investigate the molecular activities in different compartments around the bone-anchored hearing system (BAHS) with either electropolished or machined abutments and to correlate these activities with clinical and microbiological findings. Materials and methods: Twelve patients received machined or electropolished abutments after implant installation of BAHS. Peri-abutment fluid and tissue were collected from baseline to 12 months. Gene expression of cytokines and factors related to tissue healing and inflammation, regeneration and remodelling, as well as bacterial recognition were determined using quantitative-polymerase chain reaction (qPCR). The clinical status was evaluated using the Holgers scoring system, and bacterial colonisation was investigated by culturing. Results: The gene expression of inflammatory cytokines (IL-8, IL-1β, and IL-10) and bacteria-related Toll-like receptors (2 and 4) was higher in the peri-abutment fluid than at baseline and in the peri-abutment tissue at 3 and 12 months. Conversely, the expression of genes related to tissue regeneration (Coll1a1 and FOXO1) was higher in the tissue samples than in the peri-abutment fluid at 3 and 12 months. Electropolished abutments triggered higher expression of inflammatory cytokines (IL-8 and IL-1β) (in peri-abutment fluid) and regeneration factor FOXO1 (in peri-abutment tissue) than machined abutments. Several cytokine genes in the peri-abutment fluid correlated positively with the detection of aerobes, anaerobes and Staphylococcus species, as well as with high Holger scores. Conclusion: This study provides unprecedented molecular information on the biological processes of BAHS. Despite being apparently healed, the peri-abutment fluid harbours prolonged inflammatory activity in conjunction with the presence of different bacterial species. An electropolished abutment surface appears to be associated with stronger proinflammatory activity than that with a machined surface. The analysis of the peri-abutment fluid deserves further verification as a non-invasive sampling and diagnostic procedure of BAHS.
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| 34. |
- Hutchinson, Daniel, et al.
(författare)
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Highly Customizable Bone Fracture Fixation through the Marriage of Composites and Screws
- 2021
-
Ingår i: Advanced Functional Materials. - : John Wiley and Sons Inc. - 1616-301X .- 1616-3028. ; 31:41
-
Tidskriftsartikel (refereegranskat)abstract
- Open reduction internal fixation (ORIF) metal plates provide exceptional support for unstable bone fractures; however, they often result in debilitating soft-tissue adhesions and their rigid shape cannot be easily customized by surgeons. In this work, a surgically feasible ORIF methodology, called AdhFix, is developed by combining screws with polymer/hydroxyapatite composites, which are applied and shaped in situ before being rapidly cured on demand via high-energy visible-light-induced thiol–ene coupling chemistry. The method is developed on porcine metacarpals with transverse and multifragmented fractures, resulting in strong and stable fixations with a bending rigidity of 0.28 (0.03) N m2 and a maximum load before break of 220 (15) N. Evaluations on human cadaver hands with proximal phalanx fractures show that AdhFix withstands the forces from finger flexing exercises, while short- and long-term in vivo rat femur fracture models show that AdhFix successfully supports bone healing without degradation, adverse effects, or soft-tissue adhesions. This procedure represents a radical new approach to fracture fixation, which grants surgeons unparalleled customizability and does not result in soft-tissue adhesions. © 2021 The Authors.
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| 35. |
- Muneer, Faraz, et al.
(författare)
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Innovative Green Way to Design Biobased Electrospun Fibers from Wheat Gluten and These Fibers' Potential as Absorbents of Biofluids
- 2022
-
Ingår i: ACS Environmental Au. - : American Chemical Society (ACS). - 2694-2518. ; 2:3, s. 232-241
-
Tidskriftsartikel (refereegranskat)abstract
- In this study, a new method was developed to successfully design sustainable microfibers from wheat gluten proteins using a nonreducing solvent and electrospinning. We explored the morphology by X-ray tomography, scanning electron microscopy (SEM), and confocal laser scanning microscopy (CLSM), protein chemistry and cross-linking by size exclusion-high-performance liquid chromatography (SE-HPLC), and secondary structure by Fourier transform infrared spectroscopy (FT-IR) of fibers containing 15 and 20% of gluten. The impact of heat (130 °C) post-treatment on the polymerization properties of fibers and their absorption performance in different biofluids were also evaluated. The fibers with 20% gluten showed a uniform architecture supported by a relatively stronger fibrous network as compared to irregular and brittle fibers from 15% gluten. Heat treatment of fibers increased the protein cross-linking in all electrospun fibers as compared to the non-heat-treated fibers, as evidenced by SE-HPLC. An increase in the amount of α-helices and random coils was observed in the proteins of all of the heat-treated fibers compared to the nontreated fibers by FT-IR. This suggested that the heat treatment contributed positively to the gluten protein's chemical rearrangements, e.g., aggregation, new hydrogen and isopeptide bonding, and conversion of some of the sulfhydryl groups into disulfide cross-links, contributing positively to the functional performance. The heat-treated electrospun fibers with 20% gluten showed a very attractive blood absorption capacity (323%) and reasonable stability in phosphate-buffered saline (PBS) buffer compared to 15% gluten fibers and non-heat-treated fibers. Cotton-like fiber architecture, high blood absorption capacity, and reasonable stability in PBS buffer are properties desired for absorbents of biofluids and should be further explored in healthcare and medical applications.
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| 36. |
- Cardemil, Carina
(författare)
-
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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| 37. |
- Apelgren, Peter, et al.
(författare)
-
Vascularization of tissue engineered cartilage-Sequential in vivo MRI display functional blood circulation
- 2021
-
Ingår i: Biomaterials. - : Elsevier BV. - 0142-9612 .- 1878-5905. ; 276
-
Tidskriftsartikel (refereegranskat)abstract
- Establishing functional circulation in bioengineered tissue after implantation is vital for the delivery of oxygen and nutrients to the cells. Native cartilage is avascular and thrives on diffusion, which in turn depends on proximity to circulation. Here, we investigate whether a gridded three-dimensional (3D) bioprinted construct would allow ingrowth of blood vessels and thus prove a functional concept for vascularization of bioengineered tissue. Twenty 10 x 10 x 3-mm 3Dbioprinted nanocellulose constructs containing human nasal chondrocytes or cell-free controls were subcutaneously implanted in 20 nude mice. Over the next 3 months, the mice were sequentially imaged with a 7 T small-animal MRI system, and the diffusion and perfusion parameters were analyzed. The chondrocytes survived and proliferated, and the shape of the constructs was well preserved. The diffusion coefficient was high and well preserved over time. The perfusion and diffusion patterns shown by MRI suggested that blood vessels develop over time in the 3D bioprinted constructs; the vessels were confirmed by histology and immunohistochemistry. We conclude that 3D bioprinted tissue with a gridded structure allows ingrowth of blood vessels and has the potential to be vascularized from the host. This is an essential step to take bioengineered tissue from the bench to clinical practice.
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| 38. |
- 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
-
Ingår i: Biofabrication. - : Institute of Physics (IOP). - 1758-5090 .- 1758-5082. ; 5:2, s. 025009-
-
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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| 39. |
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| 40. |
- Wickham, Abeni, et al.
(författare)
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Near-Infrared Emitting and Pro-Angiogenic Electrospun Conjugated Polymer Scaffold for Optical Biomaterial Tracking
- 2015
-
Ingår i: Advanced Functional Materials. - : Wiley: 12 months. - 1616-301X .- 1616-3028. ; 25:27, s. 4274-4281
-
Tidskriftsartikel (refereegranskat)abstract
- Noninvasive tracking of biomaterials is vital for determining the fate and degradation of an implant in vivo, and to show its role in tissue regeneration. Current biomaterials have no inherent capacity to enable tracing but require labeling with, for example, fluorescent dyes, or nanoparticles. Here a novel biocompatible fully conjugated electrospun scaffold is described, based on a semiconducting luminescent polymer that can be visualized in situ after implantation using fluorescence imaging. The polymer, poly [2,3-bis-(3-octyloxyphenyl)quinoxaline-5,8-diyl-alt -thiophene-2,5-diyl] (TQ1), is electrospun to form a fibrous mat. The fibers display fluorescence emission in the near-infrared region with lifetimes in the sub-nanosecond range, optimal for in situ imaging. The material shows no cytotoxic behaviors for embryonic chicken cardiomyocytes and mouse myoblasts, and cells migrate onto the TQ1 fibers even in the presence of a collagen substrate. Subcutaneous implantations of the material in rats show incorporation of the TQ1 fibers within the tissue, with limited inflammation and a preponderance of small capillaries around the fibers. The fluorescent properties of the TQ1 fibers are fully retained for up to 90 d following implantation and they can be clearly visualized in tissue using fluorescence and lifetime imaging, thus making it both a pro-angiogenic and traceable biomaterial.
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| 41. |
- 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-
-
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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| 42. |
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| 43. |
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| 44. |
- Apelgren, Peter, et al.
(författare)
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In Vivo Human Cartilage Formation in Three-Dimensional Bioprinted Constructs with a Novel Bacterial Nanocellulose Bioink
- 2019
-
Ingår i: Acs Biomaterials Science & Engineering. - : American Chemical Society (ACS). - 2373-9878. ; 5:5, s. 2482-2490
-
Tidskriftsartikel (refereegranskat)abstract
- Bacterial nanocellulose (BNC) is a 3D network of nanofibrils exhibiting excellent biocompatibility. Here, we present the aqueous counter collision (ACC) method of BNC disassembly to create bioink with suitable properties for cartilage-specific 3D-bioprinting. BNC was disentangled by ACC, and fibril characteristics were analyzed. Bioink printing fidelity and shear-thinning properties were evaluated. Cell-laden bioprinted grid constructs (5 X 5 X 1 mm(3)) containing human nasal chondrocytes (10 M mL(-1)) were implanted in nude mice and explanted after 30 and 60 days. Both ACC and hydrolysis resulted in significantly reduced fiber lengths, with ACC resulting in longer fibrils and fewer negative charges relative to hydrolysis. Moreover, ACC-BNC bioink showed outstanding printability, postprinting mechanical stability, and structural integrity. In vivo, cell-laden structures were rapidly integrated, maintained structural integrity, and showed chondrocyte proliferation, with 32.8 +/- 13.8 cells per mm(2) observed after 30 days and 85.6 +/- 30.0 cells per mm(2) at day 60 (p = 0.002). Furthermore, a full-thickness skin graft was attached and integrated completely on top of the 3D-bioprinted construct. The novel ACC disentanglement technique makes BNC biomaterial highly suitable for 3D-bioprinting and clinical translation, suggesting cell-laden 3D-bioprinted ACC-BNC as a promising solution for cartilage repair.
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| 45. |
- Engberg, Anna E., et al.
(författare)
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Prediction of inflammatory responses induced by biomaterials in contact with human blood using protein fingerprint from plasma
- 2015
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Ingår i: Biomaterials. - : Elsevier BV. - 0142-9612 .- 1878-5905. ; 36, s. 55-65
-
Tidskriftsartikel (refereegranskat)abstract
- Inappropriate complement activation is often responsible for incompatibility reactions that occur when biomaterials are used. Complement activation is therefore a criterion included in legislation regarding biomaterials testing. However, no consensus is yet available regarding appropriate complement-activation-related test parameters. We examined protein adsorption in plasma and complement activation/cytokine release in whole blood incubated with well-characterized polymers. Strong correlations were found between the ratio of C4 to its inhibitor C4BP and generation of 10 (mainly pro-inflammatory) cytokines, including IL-17, IFN-gamma, and IL-6. The levels of complement activation products correlated weakly (C3a) or not at all (C5a, sC5b-9), confirming their poor predictive values. We have demonstrated a direct correlation between downstream biological effects and the proteins initially adhering to an artificial surface after contact with blood. Consequently, we propose the C4/C4BP ratio as a robust, predictor of biocompatibility with superior specificity and sensitivity over the current gold standard. (C) 2014 Elsevier Ltd. All rights reserved.
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| 46. |
- Gatenholm, Paul, 1956, et al.
(författare)
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Effect of cultivation conditions on the structure and morphological properties of BNC biomaterials with a focus on vascular grafts
- 2016
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Ingår i: Bacterial NanoCellulose: A Sophisticated Multifunctional Material. - Boca Raton : CRC Press. - 9781439869925 ; , s. 19-42
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- 20 New materials that are not thrombogenic and have mechanical properties that mimic the native blood vessel are in very great demand. Nanocellulose produced by the bacteria Gluconacetobacter xylinus is a biomaterial that has gained interest in the field of tissue engineering because of its unique properties, such as great mechanical strength, high water content (around 99%), and the ability to be shaped into three-dimensional structures during biosynthesis. The fabrication process of bacterial nanocellulose (BNC) vascular grafts is very unique because the material synthesis and product formation takes place simultaneously. The bio mechanical performance, which includes rupture pressure and compliance along with biological response (endothelialization, blood compatibility, etc.), is dependent on the morphology of a fibrillar network. The network formation is affected by cellulose assembly and bacteria motion, proliferation rate, and other factors. An understanding of the effects of cultivation conditions on BNC network formation is therefore of great importance.
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| 47. |
- Hansson, Magnus L., et al.
(författare)
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Artificial spider silk supports and guides neurite extension in vitro
- 2021
-
Ingår i: The FASEB Journal. - : John Wiley & Sons. - 0892-6638 .- 1530-6860. ; 35:11
-
Tidskriftsartikel (refereegranskat)abstract
- Surgical intervention with the use of autografts is considered the gold standard to treat peripheral nerve injuries. However, a biomaterial that supports and guides nerve growth would be an attractive alternative to overcome problems with limited availability, morbidity at the site of harvest, and nerve mismatches related to autografts. Native spider silk is a promising material for construction of nerve guidance conduit (NGC), as it enables regeneration of cm-long nerve injuries in sheep, but regulatory requirements for medical devices demand synthetic materials. Here, we use a recombinant spider silk protein (NT2RepCT) and a functionalized variant carrying a peptide derived from vitronectin (VN-NT2RepCT) as substrates for nerve growth support and neurite extension, using a dorsal root ganglion cell line, ND7/23. Two-dimensional coatings were benchmarked against poly-d-lysine and recombinant laminins. Both spider silk coatings performed as the control substrates with regards to proliferation, survival, and neurite growth. Furthermore, NT2RepCT and VN-NT2RepCT spun into continuous fibers in a biomimetic spinning set-up support cell survival, neurite growth, and guidance to an even larger extent than native spider silk. Thus, artificial spider silk is a promising biomaterial for development of NGCs.
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| 48. |
- Karlsson, Johan, 1984, et al.
(författare)
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Stem cell homing using local delivery of plerixafor and stromal derived growth factor-1alpha for improved bone regeneration around Ti-implants
- 2016
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Ingår i: Journal of Biomedical Materials Research - Part A. - : Wiley. - 1552-4965 .- 1549-3296. ; 104:10, s. 2466-2475
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Tidskriftsartikel (refereegranskat)abstract
- Triggering of the early healing events, including the recruitment of progenitor cells, has been suggested to promote bone regeneration. In implantology, local drug release technologies could provide an attractive approach to promote tissue regeneration. In this study, we targeted the chemotactic SDF-1a/CXCR4 axis that is responsible e.g. for the homing of stem cells to trauma sites. This was achieved by local delivery of plerixafor, an antagonist to CXCR4, and/or SDF-1a from titanium implants coated with mesoporous titania thin films with a pore size of 7.5 nm. In vitro drug delivery experiments demonstrated that the mesoporous coating provided a high drug loading capacity and controlled release. The subsequent in vivo study in rat tibia showed beneficial effects with respect to bone-implant anchorage and bone-formation along the surface of the implants when plerixafor and SDF-1a were delivered locally. The effect was most prominent by the finding that the combination of the drugs significantly improved the mechanical bone anchorage. These observations suggest that titanium implants with local delivery of drugs for enhanced local recruitment of progenitor cells have the ability to promote osseointegration. This approach may provide a potential strategy for the development of novel implant treatments.
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| 49. |
- Pujari-Palmer, Michael, et al.
(författare)
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A Novel Class of Injectable Bioceramics That Glue Tissues and Biomaterials
- 2018
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Ingår i: Materials. - : MDPI AG. - 1996-1944. ; 11:12
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Tidskriftsartikel (refereegranskat)abstract
- Calcium phosphate cements (CPCs) are clinically effective void fillers that are capable of bridging calcified tissue defects and facilitating regeneration. However, CPCs are completely synthetic/inorganic, unlike the calcium phosphate that is found in calcified tissues, and they lack an architectural organization, controlled assembly mechanisms, and have moderate biomechanical strength, which limits their clinical effectiveness. Herein, we describe a new class of bioinspired CPCs that can glue tissues together and bond tissues to metallic and polymeric biomaterials. Surprisingly, alpha tricalcium phosphate cements that are modified with simple phosphorylated amino acid monomers of phosphoserine (PM-CPCs) bond tissues up to 40-fold stronger (2.5-4 MPa) than commercial cyanoacrylates (0.1 MPa), and 100-fold stronger than surgical fibrin glue (0.04 MPa), when cured in wet-field conditions. In addition to adhesion, phosphoserine creates other novel properties in bioceramics, including a nanoscale organic/inorganic composite microstructure, and templating of nanoscale amorphous calcium phosphate nucleation. PM-CPCs are made of the biocompatible precursors calcium, phosphate, and amino acid, and these represent the first amorphous nano-ceramic composites that are stable in liquids.
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| 50. |
- Shah, Furqan A., et al.
(författare)
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Bioactive glass and glass-ceramic scaffolds for bone tissue engineering
- 2018
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Ingår i: Bioactive Glasses (Second Edition). - 9780081009369 ; , s. 201-33
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Bioactive glasses and glass-ceramics are a diverse group of materials possessing a unique set of physicochemical properties that make them useful for bone repair. Scaffolds for bone tissue engineering are subject to many requirements including biocompatibility, osteogenesis, biodegradability, and mechanical competence, all of which must be considered in the design features. This chapter addresses various scaffold fabrication techniques for melt-derived and sol-gel-derived compositions, polymer-based organic-inorganic composites, calcium phosphate-based inorganic-inorganic composites, bioactive bone cements, scaffolds based on glass compositions containing specific therapeutic ions, and hybrid materials where the organic and inorganic phases interact at the molecular level. The most important achievements, challenges and potential solutions, as well as the most promising areas of future research involving bioactive glasses and glass-ceramics for bone tissue engineering are presented.
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