| 1. |
- Palmquist, Anders, 1977, et al.
(author)
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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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In: Acta Biomaterialia. - : Elsevier BV. - 1742-7061 .- 1878-7568. ; 156, s. 125-145
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Research review (peer-reviewed)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.
(author)
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Evidence for wastewaters as environments where mobile antibiotic resistance genes emerge
- 2023
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In: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 6
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Journal article (peer-reviewed)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-
(author)
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Extracellular Matrix Based Materials for Tissue Engineering
- 2010
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Doctoral thesis (other academic/artistic)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
(author)
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Hyperthermia-responsive liposomal systems
- 2015
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Doctoral thesis (other academic/artistic)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.
(author)
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AHA! festival 2015
- 2015
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Other publication (other academic/artistic)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.
(author)
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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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In: Acta Biomaterialia. - : Elsevier. - 1742-7061 .- 1878-7568. ; 136, s. 582-591
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Journal article (peer-reviewed)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.
(author)
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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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In: PLosOne. - : Public Library of Science (PLoS). - 1932-6203. ; 8:12
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Journal article (peer-reviewed)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.
(author)
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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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In: Journal of materials science. Materials in medicine. - : Springer. - 0957-4530 .- 1573-4838. ; 20:11, s. 2337-2347
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Journal article (peer-reviewed)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.
(author)
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Chondrocytes and stem cells in 3D-bioprinted structures create human cartilage in vivo.
- 2017
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In: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 12:12
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Journal article (peer-reviewed)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.
(author)
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Mineralization at Titanium Surfaces is a Two-Step Process.
- 2016
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In: Journal of functional biomaterials. - : MDPI AG. - 2079-4983. ; 7:1
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Journal article (peer-reviewed)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.
(author)
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Biomimetic spinning of artificial spider silk from a chimeric minispidroin
- 2017
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In: Nature Chemical Biology. - : Springer Science and Business Media LLC. - 1552-4450 .- 1552-4469. ; 254
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Journal article (peer-reviewed)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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| 21. |
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| 22. |
- Nilsson, Per H., 1980-
(author)
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Interactions between platelets and complement with implications for the regulation at surfaces
- 2012
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Doctoral thesis (other academic/artistic)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.
(author)
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Biomaterial Integration in the Joint: Pathological Considerations, Immunomodulation, and the Extracellular Matrix
- 2022
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In: Macromolecular Bioscience. - : Wiley. - 1616-5195 .- 1616-5187. ; 22:7
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Research review (peer-reviewed)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-
(author)
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Synthesis of xyloglucan oligo- and polysaccharides with glycosynthase technology
- 2009
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Licentiate thesis (other academic/artistic)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
(author)
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Polyelectrolyte Brush Electrodes for Protein Capture and Release
- 2020
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Doctoral thesis (other academic/artistic)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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