| 1. |
- Atefyekta, Saba, 1987, et al.
(författare)
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Antimicrobial Peptide-Functionalized Mesoporous Hydrogels
- 2021
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Ingår i: ACS Biomaterials Science & Engineering. - : American Chemical Society (ACS). - 2373-9878. ; 7:4, s. 1693-1702
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Tidskriftsartikel (refereegranskat)abstract
- Antimicrobial peptides (AMPs) are seen as a promising replacement to conventional antibiotics for the prevention of skin wound infections. However, due to the short half-life of AMPs in biological environments, such as blood, their use in clinical applications has been limited. The covalent immobilization of AMPs onto suitable substrates is an effective solution to create contact-killing surfaces with increased long-term stability. In this work, an antimicrobial peptide, RRPRPRPRPWWWW-NH2 (RRP9W4N), was covalently attached to amphiphilic and ordered mesoporous Pluronic F127 hydrogels made of cross-linked lyotropic liquid crystals through 1-ethyl-3-(3-(dimethylamino)propyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS) chemistry. The AMP-hydrogels showed high antibacterial activity against Staphylococcus epidermidis, Staphylococcus aureus, Pseudomonas aeruginosa, methicillin-resistant S. aureus (MRSA), and multidrug-resistant Escherichia coli for up to 24 h. Furthermore, the AMP-hydrogels did not present any toxicity to human fibroblasts. The AMPs retained their antimicrobial activity up to 48 h in human blood serum, which is a significant increase in stability compared to when used in dissolved state. A pilot in vivo rat model showed 10-100x less viable counts of S. aureus on AMP-hydrogels compared with control hydrogels during the first 3 days of infection. Studies performed on human whole blood showed that blood coagulated more readily in the presence of AMP-hydrogels as compared to hydrogels without AMPs, indicating potential hemostatic activity. Overall, the results suggest that the combination of amphiphilic hydrogels with covalently bonded AMPs has potential to be used as antibacterial wound dressing material to reduce infections and promote hemostatic activity as an alternative to antibiotics or other antimicrobial agents, whose use should be restricted.
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| 2. |
- Basu, Alex, et al.
(författare)
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Hemocompatibility of Ca2+-Crosslinked Nanocellulose Hydrogels : Toward Efficient Management of Hemostasis
- 2017
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Ingår i: Macromolecular Bioscience. - : Wiley. - 1616-5187 .- 1616-5195. ; 17:11
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Tidskriftsartikel (refereegranskat)abstract
- The present work investigates Ca2+-crosslinked nanofibrillated cellulose hydrogels as potential hemostatic wound dressings by studying core interactions between the materials and a central component of wounds and wound healing—the blood. Hydrogels of wood-derived anionic nanofibrillated cellulose (NFC) and NFC hydrogels that incorporate kaolin or collagen are studied in an in vitro whole blood model and with platelet-free plasma assays. The evaluation of thrombin and factor XIIa formation, platelet reduction, and the release of activated complement system proteins, shows that the NFC hydrogel efficiently triggered blood coagulation, with a rapid onset of clot formation, while displaying basal complement system activation. By using the NFC hydrogel as a carrier of kaolin, the onset of hemostasis is further boosted, while the NFC hydrogel containing collagen exhibits blood activating properties comparable to the anionic NFC hydrogel. The herein studied NFC hydrogels demonstrate great potential for being part of advanced wound healing dressings that can be tuned to target certain wounds (e.g., strongly hemorrhaging ones) or specific phases of the wound healing process for optimal wound management.
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| 3. |
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| 4. |
- Bexborn, Fredrik, et al.
(författare)
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Hirudin versus heparin for use in whole blood in vitro biocompatibility models
- 2009
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Ingår i: Journal of Biomedical Materials Research. Part A. - Hoboken, NJ, US : John Wiley & Sons Inc. - 1549-3296 .- 1552-4965. ; 89A:4, s. 951-959
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Tidskriftsartikel (refereegranskat)abstract
- Background: Heparin has traditionally been a widely used anticoagulant in blood research, but has been shown to be inappropriate for work with the complement system because of its complement-interacting properties. In this work, we have compared the effects of heparin with those of the specific thrombin inhibitor hirudin on complement and blood cells in vitro. Methods: Whole blood collected in the presence of hirudin (50 µg/mL) or heparin (1 IU/mL) was incubated in the slide chamber model. The plasma was analyzed for complement activation markers C3a and sC5b-9, and the polyvinylchloride test slides were stained for adhering cells. The integrity of the complement system was tested by incubating serum and hirudin-treated plasma in the presence of various activating agents.Results: In contrast to heparin, the addition of hirudin generally preserved the complement reactivity, and complement activation in hirudin plasma closely resembled that in normal serum. Importantly, immunochemical staining of surface-bound cells demonstrated the inducible expression of tissue factor on bound monocytes from hirudin-treated blood, an effect that was completely abolished in heparin-treated blood.Conclusion: Our results indicate that hirudin as an anticoagulant produces more physiological conditions than heparin, making hirudin well-suited for in vitro studies, especially those addressing the regulation of cellular processes.
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| 5. |
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| 6. |
- Ek, Rebecca, 1985-, et al.
(författare)
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Blood coagulation on electron beam melted implant surfaces, implications for bone growth
- 2011
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Ingår i: Proccedings of EBS 2011. - Dublin.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- INTRODUCTIONImplants for arthroplasty, plates and screws for orthopedics, maxillofacial and dentistry are more frequently being customised. Ti and CoCr alloys are common materials for bone implants. Surface roughness, porosity and choice of material may have an impact on the bone ingrowth. EBM (Electron Beam Melting) is a 3D-printing technique melting metallic powder layer by layer according to the corresponding CAD (Computer Aided Design) model of implants1.With EBM technology customised implants can be manufactured with a lower cost compared to conventional technologies2. Implants for bone replacement made from CT images with EBM technology will fit accurate and lead to simpler and better planed surgeries also3. The EBM technique, as such, is always resulting with rough surface on the implants (typically 20-45µm). That roughness can be controlled, in some extent, by changing the process parameters. Some authors claim that roughened surfaces are promoting bone ingrowth4.This work was aiming on the question: are EBM made surfaces good for bone ingrowth and is it possible to change the bone ingrowth by varying the machine settings? In order to answer this question a number of coin like specimens of CoCr were manufactured with the different surface roughness. The blood chamber model has shown how the first steps of bone healing were proceeding on specimen surfaces, indicating how the coagulation and complement systems can behave in vivo5. EXPERIMENTAL METHODSThe manufacture of the test specimens was carried out with Arcam A2 EBM® equipment. Process parameters were changed in the software EBM controle6 and three groups of eight specimens with different parameter setting were made. The specimens were then tested with whole blood from two individuals in a modified version of the blood chamber model named above7. Surface roughness was characterised with a stylus profiler Dektak® 6M. RESULTS AND DISCUSSIONTable 1 percents Ra (average roughness) and plt (platelets) activated for each group. Table 1group Ra mean std plt mean std1 35.0µm 3.24µm 92.9% 5.25%2 28.5µm 2.14µm 85.3% 7.61%3 28.2µm 1.75µm 84.4% 10.3% The results indicate that rougher surfaces are more thrombogenic which could imply that they are more suitable for bone ingrowth then smooth surfaces. Increase of total surface area (due to larger roughness) might be a reason for the improved trombogenic response. Figure 1 shows how many platelets were stuck on the specimen surfaces. Horizontal lines represent mean values and standard deviation. CONCLUSIONThe surface properties of EBM produced implants are affected by the made parameters. The results in Figure 1 corresponds well with previous results that rougher surfaces promotes bone ingrowth4. The increased thrombogenicity and platelet binding with rougher surfaces indicates that EBM made surfaces can affect the final bone response and will possibly suit as implant material. REFERENCES1. Raennar, L.E., et al., Efficientcooling with tool inserts manufactured by electronbeam melting. Rapid Prototyping Journal. 13:128-35, 20072. Cronskaer, M. Applications of Electron Beam Melting to Titanium Hip Stem Implants3. Mazzoli, A., et al., Direct fabrication through electron beam melting technology of custom cranial implants designed in a PHANToM-based haptic environment. Materials and Design. 30:318-3192, 20094. Frosch, K.H., et al., Metallic Biomaterials in Skeletal Rapair. Eur J Trauma. 32:149-59, 20065. Thor A., et al.. The role of whole blood in thrombin generation in contact with various titanium surfaces. Biomaterials. 28:966-97, 20076. Arcam AB (www.arcam.com)7. Hong, J., et al., A new in vitro model to study interaction between whole blood and biomaterials. Studies of platelet and coagulation activation acid the effect of aspirin. Biomaterials. 20:603-611, 1999
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| 7. |
- Ekstrand-Hammarström, Barbro, et al.
(författare)
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TiO2 nanoparticles tested in a novel screening whole human blood model of toxicity trigger adverse activation of the kallikrein system at low concentrations
- 2015
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Ingår i: Biomaterials. - : Elsevier BV. - 0142-9612 .- 1878-5905. ; 51, s. 58-68
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Tidskriftsartikel (refereegranskat)abstract
- There is a compelling need to understand and assess the toxicity of industrially produced nanoparticles (NPs). In order to appreciate the long-term effects of NPs, sensitive human-based screening tests that comprehensively map the NP properties are needed to detect possible toxic mechanisms. Animal models can only be used in a limited number of test applications and are subject to ethical concerns, and the interpretation of experiments in animals is also distorted by the species differences. Here, we present a novel easy-to-perform highly sensitive whole-blood model using fresh non-anticoagulated human blood, which most justly reflects complex biological cross talks in a human system. As a demonstrator of the tests versatility, we evaluated the toxicity of TiO2 NPs that are widely used in various applications and otherwise considered to have relatively low toxic properties. We show that TiO2 NPs at very low concentrations (50 ng/mL) induce strong activation of the contact system, which in this model elicits thromboinflammation. These data are in line with the finding of components of the contact system in the protein corona of the TiO2 NPs after exposure to blood. The contact system activation may lead to both thrombotic reactions and generation of bradykinin, thereby representing fuel for chronic inflammation in vivo and potentially long-term risk of autoimmunity, arteriosclerosis and cancer. These results support the notion that this novel whole-blood model represents an important contribution to testing of NP toxicity. (C) 2015 Elsevier Ltd. All rights reserved.
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| 8. |
- Ferraz, Natalia, 1976-
(författare)
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Effect of Surface Nanotopography on Blood-Biomaterial Interactions
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Biologically inspired materials are being developed with the aim of improving the integration of medical implants and minimizing non-desirable host reactions. A promising strategy is the design of topographically patterned surfaces that resemble those found in the extracellular environment. Nanoporous alumina has been recognized as a potential biomaterial and as an important template for the fabrication of nanostructures. In this thesis in vitro studies were done to elucidate the role of alumina nanoporosity on the inflammatory response. Specifically, by comparing alumina membranes with two pore sizes (20 and 200 nm in diameter). Complement and platelet activation were evaluated as well as monocyte/macrophage behaviour. Whole blood was incubated with the alumina membranes and thereafter the biomaterial surfaces were evaluated in terms of protein and platelet adhesion as well as procoagulant properties. The fluid phase was analyzed for complement activation products and platelet activation markers. Besides, human mononuclear cells were cultured on the alumina membranes and cell adhesion, viability, morphology and release of pro-inflammatory cytokines were evaluated. The results indicated that nanoporous alumina with 200 nm pores promotes higher complement activation than alumina with 20 nm pores. In addition, platelet response to nanoporous alumina was found to be highly dependent on the material porosity, as reflected by differences in adhesion, PMP generation and procoagulant characteristics. A clear difference in monocyte/macrophage adhesion and activation was found between the two pore size alumina membranes. Few but highly activated cells adhered to the 200 nm membrane in contrast to many but less activated monocytes/macrophages on the 20 nm surface. The outcome of this work emphasizes that nanotopography plays an important role in the host response to biomaterials. Better understanding of molecular interactions on nano-level will undoubtedly play a significant role in biomaterial implant development and will contribute to design strategies for controlling specific biological events.
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| 9. |
- Ferraz, Natalia, et al.
(författare)
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Haemocompatibility and ion exchange capability of nanocellulose polypyrrole membranes intended for blood purification
- 2012
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Ingår i: Journal of the Royal Society Interface. - : The Royal Society. - 1742-5689 .- 1742-5662. ; 9:73, s. 1943-1955
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Tidskriftsartikel (refereegranskat)abstract
- Composites of nanocellulose and the conductive polymer polypyrrole (PPy) are presented as candidates for a new generation of haemodialysis membranes. The composites may combine active ion exchange with passive ultrafiltration, and the large surface area (about 80 m2 g−1) could potentially provide compact dialysers. Herein, the haemocompatibility of the novel membranes and the feasibility of effectively removing small uraemic toxins by potential-controlled ion exchange were studied. The thrombogenic properties of the composites were improved by applying a stable heparin coating. In terms of platelet adhesion and thrombin generation, the composites were comparable with haemocompatible polymer polysulphone, and regarding complement activation, the composites were more biocompatible than commercially available membranes. It was possible to extract phosphate and oxalate ions from solutions with physiological pH and the same tonicity as that of the blood. The exchange capacity of the materials was found to be 600 ± 26 and 706 ± 31 μmol g−1 in a 0.1 M solution (pH 7.4) and in an isotonic solution of phosphate, respectively. The corresponding values with oxalate were 523 ± 5 in a 0.1 M solution (pH 7.4) and 610 ± 1 μmol g−1 in an isotonic solution. The heparinized PPy–cellulose composite is consequently a promising haemodialysis material, with respect to both potential-controlled extraction of small uraemic toxins and haemocompatibility.
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| 10. |
- Ferraz, Natalia, et al.
(författare)
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Influence of nanoporesize on platelet adhesion and activation
- 2008
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Ingår i: Journal of materials science. Materials in medicine. - : Springer Science and Business Media LLC. - 0957-4530 .- 1573-4838. ; 19:9, s. 3115-21
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Tidskriftsartikel (refereegranskat)abstract
- In this study we have evaluated the influence of biomaterial nano-topography on platelet adhesion and activation. Nano-porous alumina membranes with pore diameters of 20 and 200 nm were incubated with whole blood and platelet rich plasma. Platelet number, adhesion and activation were determined by using a coulter hematology analyzer, scanning electron microscopy, immunocytochemical staining in combination with light microscopy and by enzyme immunoassay. Special attention was paid to cell morphology, microparticle generation, P-selectin expression and beta-TG production. Very few platelets were found on the 200 nm alumina as compared to the 20 nm membrane. The platelets found on the 20 nm membrane showed signs of activation such as spread morphology and protruding filipodia as well as P-selectin expression. However no microparticles were detected on this surface. Despite the fact that very few platelets were found on the 200 nm alumina in contrast to the 20 nm membrane many microparticles were detected on this surface. Interestingly, all microparticles were found inside circular shaped areas of approximately 3 mum in diameter. Since this is the approximate size of a platelet we speculate that this is evidence of transient, non-adherent platelet contact with the surface, which has triggered platelet microparticle generation. To the authors knowledge, this is the first study that demonstrates how nanotexture can influence platelet microparticle generation. The study highlights the importance of understanding molecular and cellular events on nano-level when designing new biomaterials.
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| 11. |
- Ferraz, Natalia, et al.
(författare)
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Nanoporesize affects complement activation
- 2008
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Ingår i: Journal of biomedical materials research. Part A. - : Wiley. - 1552-4965 .- 1549-3296. ; 87:3, s. 575-81
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Tidskriftsartikel (refereegranskat)abstract
- In the present study, we have shown the vast importance of biomaterial nanotexture when evaluating inflammatory response. For the first time in an in vitro whole blood system, we have proven that a small increase in nanoporesize, specifically 180 nm (from 20 to 200 nm), has a huge effect on the complement system. The study was done using nanoporous aluminiumoxide, a material that previously has been evaluated for potential implant use, showing good biocompatibility. This material can easily be manufactured with different pore sizes making it an excellent candidate to govern specific protein and cellular events at the tissue-material interface. We performed whole blood studies, looking at complement activation after blood contact with two pore size alumina membranes (pore diameters, 20 and 200 nm). The fluid phase was analyzed for complement soluble components, C3a and sC5b-9. In addition, surface adsorbed proteins were eluted and dot blots were performed to detect IgG, IgM, C1q, and C3. All results point to the fact that 200 nm pore size membranes are more complement activating. Significantly, higher values of complement soluble components were found after whole blood contact with 200 nm alumina and all studied proteins adsorbed more readily to this membrane than to the 20 nm pore size membrane. We hypothesize that the difference in complement activation between our two test materials is caused by the type and the amount of adsorbed proteins, as well as their conformation and orientation. The different protein patterns created on the two alumina membranes are most likely a consequence of the material topography.
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| 12. |
- Ferraz, Natalia, 1976-, et al.
(författare)
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Nanoporosity of alumina surfaces induces different patterns of activation in adhering monocytes/macrophages
- 2010
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Ingår i: International Journal of Biomaterials. - : Hindawi Limited. - 1687-8787 .- 1687-8795. ; 2010, s. 402715-
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Tidskriftsartikel (refereegranskat)abstract
- The present study shows that alumina nanotopography affects monocyte/macrophage behaviour. Human mononuclear cells cultured on alumina membranes with pore diameters of 20 and 200 nm were evaluated in terms of cell adhesion, viability, morphology and release of pro-inflammatory cytokines. After 24 hours, cell adhesion was assessed by means of light microscopy and cell viability by measuring LDH release. The inflammatory response was evaluated by quantifying interleukin-1ß and tumour necrosis factor-α. Finally, scanning electron microscopy was used to study cell morphology. Results showed pronounced differences in cell number, morphology and cytokine release depending on the nanoporosity. Few but highly activated cells were found on the 200 nm porous alumina, while relatively larger number of cells was found on the 20 nm porous surface. However, despite their larger number, the cells adhering on the 20 nm surface exhibited reduced pro-inflammatory activity. It can be speculated that the difference in surface topography may lead to distinct protein adsorption patterns and therefore to different degree of cell activation. The data of this paper emphasize the role played by the material nanotexture in dictating cell responses and implies that nanotopography could be exploited for controlling the inflammatory response to implants.
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| 13. |
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| 14. |
- Ferraz, Natalia, 1976-, et al.
(författare)
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Procoagulant behavior and platelet microparticle generation on nanoporous alumina
- 2010
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Ingår i: Journal of biomaterials applications. - : SAGE. - 0885-3282 .- 1530-8022. ; 24:8, s. 675-692
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Tidskriftsartikel (refereegranskat)abstract
- In the present work, we have investigated platelet microparticle(PMP) generation in whole blood after contact with nanoporous alumina.Alumina membranes with pore sizes of 20 and 200nm in diameter were incubated with whole blood and the number of PMP in the fluid phase was determined by flow cytometry. The role of the complement system in PMP generation was investigated using an analog of the potent complement inhibitor compstatin. Moreover, the procoagulant activity of the two pore size membranes were compared by measuring thrombin formation. Results indicated that PMP were not present in the fluid phase after whole blood contact with either of the alumina membranes. However, scanning electron microscope micrographs clearly showed the presence of PMP clusters on the 200nm pore size alumina, while PMP were practically absent on the 20nm membrane. We probed no influence of complement activation in PMP generation and adhesion and we hypothesize that other specific material-related protein–platelet interactions are taking place. A clear difference in procoagulant activity between the membranes could also be seen, 20nm alumina showed 100% higher procoagulant activity than 200nm membrane. By combining surface evaluation and flow cytometry analyses of the fluid phase, we are able to conclude that 200nm pore size alumina promotes PMP generation and adhesion while the 20nm membrane does not appreciably cause any release or adhesion of PMP, thus indicating a direct connection between PMP generation and nanoporosity.
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| 15. |
- Ferraz, Natalia, 1976-, et al.
(författare)
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Time sequence of blood activation by nanoporous alumina : Studies on platelets and complement system
- 2010
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Ingår i: Microscopy research and technique (Print). - : Wiley-Liss Inc.. - 1059-910X .- 1097-0029. ; 73:12, s. 1101-1109
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Tidskriftsartikel (refereegranskat)abstract
- In the present work the time sequence of blood activation by alumina membranes with different porosities (20 and 200 nm in diameter) was studied. The membranes were incubated with whole blood from 2 min to 4 h. Platelet adhesion and activation in addition to complement activation were monitored at different time points. Evaluation of platelet adhesion and activation was done by determining the change in platelet number and the levels of thrombospondin-1 in the fluid phase. Scanning electron microscopy studies were done to further evaluate platelet adhesion and morphology. Immunocytochemical staining was used to evaluate the presence of CD41 and CD62P antigens on the material surface. Complement activation was monitored by measuring C3a and sC5b-9 in plasma samples by means of enzyme immunoassays. Both alumina membranes displayed similar complement activation time profiles, with levels of C3a and sC5b-9 increasing with incubation time. A statistically significant difference between the membranes was found after 60 min of incubation. Platelet activation characteristics and time profile were different between the two membranes. Platelet adhesion increased over time for the 20 nm surface, while the clusters of microparticles on the 200 nm surface did not appreciably change during the course of the experiment. The release of thrombospondin-1 increased with time for both membranes, however much later for the 200 nm alumina (240 min) as compared to the 20 nm membrane (60 min). The surface topography of the alumina most probably influence protein transition rate, which in turn affects material-platelet activation kinetics.
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| 16. |
- Fink, Helen, 1978, et al.
(författare)
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An in vitro study of blood compatibility of vascular grafts made of bacterial cellulose in comparison with conventionally-used graft materials
- 2011
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Ingår i: Journal of Biomedical Materials Research - Part A. - : Wiley. - 1549-3296 .- 1552-4965. ; 97A:1, s. 52-58
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Tidskriftsartikel (refereegranskat)abstract
- In this study we analyzed the blood compatibility of bacterial cellulose (BC) as a new biosynthetic material for use as a vascular graft. As reference materials we used expanded polytetrafluoroethylene (ePTFE) and poly(ethylene terephthalate) (PET) vascular grafts. These materials are in clinical use today. Tubes with inner diameters of both 4 (not PET) and 6 mm were tested. Heparin-coated PVC tubes (hepPVC) were used as a negative control. Platelet consumption and thrombin-antithrombin complex (TAT) were used as parameters of coagulation and for complement activation, sC3a and sC5b-9 were used. The investigated parameters were measured after 1-h exposure to freshly drawn human blood supplemented with a low dose of heparin in a Chandler loop system. The results showed that BC exhibits no significant difference in platelet consumption, as compared with PET 16 mm), ePTFE and hepPVC. The PET material consumed more platelets than any of the other materials. The TAT generation for 4 mm tubes was not significantly different between BC and the other materials. For 6 mm tubes, however, differences were observed between hepPVC and PET (p < 0.0001); BC and hepPVC (p = 0.0016); ePTFE and PET (p < 0.0001); BC and ePTFE (p = 0.0029); BC and PET (p = 0.0141). Surprisingly, considering the low platelet consumption, the complement activation parameters (sC3a and sC5b-9) were much higher for BC, as compared with the other materials for both 4 and 6 mm tubes.
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| 17. |
- Frykstrand, Sara, et al.
(författare)
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Study of mesoporous magnesium carbonate in contact with whole human blood
- 2016
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Ingår i: RSC Advances. - : Royal Society of Chemistry (RSC). - 2046-2069. ; 6:58, s. 52810-52816
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Tidskriftsartikel (refereegranskat)abstract
- The interaction of mesoporours magnesium carbonate (Upsalite) particles (50-100 mm) with human whole blood was investigated using an in vitro loop model and the effect on the complement system, blood coagulation and red blood cell lysis was assessed. The removal of Ca2+ by Upsalite and the possible exchange with and/or release of Mg2+ were explored as well. Upsalite was found to present anticoagulant properties, most probably due to the uptake of Ca2+ by the particles. No hemolytic activity was detected at Upsalite concentrations up to 1 mg ml(-1). Moderate to high levels of C3a and sC5b-9 were observed for Upsalite, however such levels were statistically different from the negative control only when the particle concentrations were 0.25 mg ml(-1) and 1.0 mg ml(-1), respectively. The presented findings are promising for the future development of mesoporous magnesium carbonate-based materials for biomedical applications.
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| 18. |
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| 19. |
- Hong, Jaan, et al.
(författare)
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A Hydrophilic Dental Implant Surface Exhibit Thrombogenic Properties In Vitro
- 2013
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Ingår i: Clinical Implant Dentistry and Related Research. - : Wiley. - 1523-0899 .- 1708-8208. ; 15:1, s. 105-112
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Tidskriftsartikel (refereegranskat)abstract
- Background: Surface modifications of dental implants have gained attention during several years and the thrombotic response from blood components with these materials has become more important during recent years.Purpose:The aims of this study were to evaluate the thrombogenic response of whole blood, in contact with clinically used dental surfaces, Sandblasted Large grit Acid etched titanium (SLA) and Sandblasted Large grit Acid etched, and chemically modified titanium with hydrophilic properties (SLActive).Methods: An in vitro slide chamber model, furnished with heparin, was used in which whole blood came in contact with slides of the test surfaces. After incubation (60-minute rotation at 22 rpm in a 37°C water bath), blood was mixed with ethylenediaminetetraacetic acid (EDTA) or citrate, further centrifuged at +4°C. Finally, plasma was collected pending analysis.Results:Whole blood in contact with surfaces resulted in significantly higher binding of platelets to the hydrophilic surface, accompanied by a significant increase of contact activation of the coagulation cascade. In addition, the platelet activation showed a similar pattern with a significant elevated release of β-TG from platelet granule.Conclusions:The conclusion that can be drawn from the results in our study is that the hydrophilic modification seems to augment the thrombogenic properties of titanium with implications for healing into bone of, that is titanium dental implants.
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| 20. |
- Hong, Jaan, et al.
(författare)
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A new in vitro model to study interaction between whole blood and biomaterials. Studies of platelet and coagulation activation and the effect of aspirin
- 1999
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Ingår i: Biomaterials. - : Elsevier. - 0142-9612 .- 1878-5905. ; 20:7, s. 603-611
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Tidskriftsartikel (refereegranskat)abstract
- We have developed a versatile in vitro chamber model with a double purpose: first, to be able to study mechanisms of bio- incompatibility, and, second, to test biomaterials at all levels of interactions, in whole blood. The use of biomaterials in the form of microscope slides as walls in the chamber makes it possible to analyse both the biomaterial surface with regard to protein and cell binding, as well as the molecular events taking place in the fluid. Incubation of blood in the chamber, for 60 min at 37°C resulted in the rapid binding of complement and coagulation proteins and of leukocytes and platelets to polyvinylchloride (PVC) slides. The cells formed a layer which more or less covered the underlying surface. Unlike complement activation, as reflected by soluble C3a and C5b-9, the thrombin—antithrombin formation was completely nullified in cell-depleted plasma. Despite the fact that throm- bin—antithrombin generation was also negligible in platelet-rich plasma, inhibition of platelet aggregation on the material surface with aspirin resulted in suppressed generation of thrombin—antithrombin complexes. Taken together, the coagulation activation in the chamber was dependent on the presence of blood cells which suggests that bound/aggregated platelets initiate a sequence of events involving leukocytes that results in coagulation activation.
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| 21. |
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| 22. |
- Hong, Jaan
(författare)
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Investigation of Incompatibility Reactions Caused by Biomaterials in Contact with Whole Blood Using a New in vitro Model.
- 2001
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis describes a new in vitro slide chamber model that makes it possible to conduct studies of molecular and cellular interactions between whole blood and biomaterials. The model proved to be a suitable tool for detection of cell and platelet binding to a biomaterial surface. It was possible to monitor activation of the blood cascade systems and cells in the fluid phase and detect surface-bound molecules.One finding was that thrombin generation is primarily triggered by FXII on a biomaterial surface since corn trypsin inhibitor, inhibited thrombin generation in blood.Another finding was that thrombin generation was dependent on variety types of blood cells, since thrombin generation was almost negligible in platelet-rich plasma. When various preparations of blood cells were used to reconstitute platelet-rich and platelet-poor plasma, erythrocytes were shown to be the most efficient cell type in triggering thrombin generation. Inhibition of platelet aggregation with aspirin and Ro44-9883 was associated with a decrease in thrombin generation, confirming that platelet activation is necessary for normal coagulation activation. These findings suggest that the central events consist of an initial low-grade generation of thrombin that involves erythrocytes and possibly leukocytes which leads to activation of platelets; and a second platelet-dependent amplification loop that produces most of the thrombin.Titanium exposed to whole blood produced high amounts of thrombin. Stainless steel and PVC, generated lower amounts. This indicates that titanium might be less suitable as a biomaterial in devices that are in direct contact with blood for prolonged time. Considering the superior osteointegrating properties of titanium and titanium's response to blood, a correlation between high thrombogenicity and good osteointegration seems to exist.Compstatin, that binds to complement component C3, effectively inhibited the generation of C3a and sC5b-9 and the binding of C3/C3 fragments to the surface. Our results suggest that a biomaterial is able to activate complement through both the classical and alternative pathways and that the classical pathway alone is able to maintain a substantial bioincompatibility reaction. The results show that complement activation is a prerequisite for activation and binding of PMNs to the surface in the in vitro model.
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| 23. |
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| 24. |
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| 25. |
- Hulander, Mats, et al.
(författare)
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Blood interactions with noble metals: coagulation and immune complement activation.
- 2009
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Ingår i: ACS applied materials & interfaces. - : American Chemical Society (ACS). - 1944-8244 .- 1944-8252. ; 1:5, s. 1053-62
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Tidskriftsartikel (refereegranskat)abstract
- Noble metals are interesting biomaterials for a number of reasons, e.g., their chemical inertness and relative mechanical softness, silver's long known antimicrobial properties, and the low allergenic response shown by gold. Although important for the final outcome of biomaterials, little is reported about early events between pure noble metals and blood. In this article, we used whole blood in the "slide chamber model" to study the activation of the immune complement activation, generation of thrombin/antithrombin (TAT) complexes, and platelet depletion from blood upon contact with silver (Ag), palladium (Pd), gold (Au), titanium (Ti), and Bactiguard, a commercial nanostructured biomaterial coating comprised of Ag, Pd, and Au. The results show the highest TAT generation and platelet depletion on Ti and Au and lower on Pd, Ag, and the Bactiguard coating. The immune complement factor 3 fragment (C3a) was generated by the surfaces in the following order: Ag > Au > Pd > Bactiguard > Ti. Quartz crystal microbalance adsorption studies with human fibrinogen displayed the highest deposition to Ag and the lowest onto the Bactiguard coating. The adsorbed amounts of fibrinogen did not correlate with thrombogenicity in terms of TAT formation and platelet surface accumulation in blood. The combined results suggest, hence, that noble metal chemistry has a different impact on the protein adsorption properties and general blood compatibility. The low thrombogenic response by the Bactiguard coating cannot be explained by any of the single noble metal properties but is likely a successful combination of the nanostructure, nanogalvanic effects, or combinatory chemical and physical materials properties.
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| 26. |
- Hulsart Billström, Gry, 1982-, et al.
(författare)
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Thromboinflammation as bioactivity assessment of H2O2-alkali modified titanium surfaces
- 2019
-
Ingår i: Journal of materials science. Materials in medicine. - : Springer Science and Business Media LLC. - 0957-4530 .- 1573-4838. ; 30:6
-
Tidskriftsartikel (refereegranskat)abstract
- The release of growth factors from platelets, mediated by the coagulation and the complement system, plays an important role in the bone formation around implants. This study aimed at exploring the thromboinflammatory response of H2O2-alkali soaked commercially pure titanium grade 2 discs exposed to whole human blood, as a way to assess the bioactivity of the discs. Commercially pure titanium grade 2 discs were modified by soaking in H2O2, NaOH and Ca(OH)2. The platelet aggregation, coagulation activation and complement activation was assessed by exposing the discs to fresh whole blood from human donors. The platelet aggregation was examined by a cell counter and the coagulation and complement activation were assessed by ELISA-measurements of the concentration of thrombin-antithrombin complex, C3a and terminal complement complex. The modified surface showed a statistically significant increased platelet aggregation, coagulation activation and complement activation compared to unexposed blood. The surface also showed a statistically significant increase of coagulation activation compared to PVC. The results of this study showed that the H2O2-alkali soaked surfaces induced a thromboinflammatory response that indicates that the surfaces are bioactive.
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| 27. |
- Hårdstedt, Maria, 1971-, et al.
(författare)
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A novel model for studies of blood-mediated long-term responses to cellular transplants
- 2015
-
Ingår i: Upsala Journal of Medical Sciences. - : Upsala Medical Society. - 0300-9734 .- 2000-1967. ; 120:1, s. 28-39
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Tidskriftsartikel (refereegranskat)abstract
- AimsInteraction between blood and bio-surfaces is important in many medical fields. With the aim of studying blood-mediated reactions to cellular transplants, we developed a whole-blood model for incubation of small volumes for up to 48 h.MethodsHeparinized polyvinyl chloride tubing was cut in suitable lengths and sealed to create small bags. Multiple bags, with fresh venous blood, were incubated attached to a rotating wheel at 37°C. Physiological variables in blood were monitored: glucose, blood gases, mono- and divalent cations and chloride ions, osmolality, coagulation (platelet consumption, thrombin-antithrombin complexes (TAT)), and complement activation (C3a and SC5b-9), haemolysis, and leukocyte viability.ResultsBasic glucose consumption was high. Glucose depletion resulted in successive elevation of extracellular potassium, while sodium and calcium ions decreased due to inhibition of energy-requiring ion pumps. Addition of glucose improved ion balance but led to metabolic acidosis. To maintain a balanced physiological environment beyond 6 h, glucose and sodium hydrogen carbonate were added regularly based on analyses of glucose, pH, ions, and osmotic pressure. With these additives haemolysis was prevented for up to 72 h and leukocyte viability better preserved. Despite using non-heparinized blood, coagulation and complement activation were lower during long-term incubations compared with addition of thromboplastin and collagen.ConclusionA novel whole-blood model for studies of blood-mediated responses to a cellular transplant is presented allowing extended observations for up to 48 h and highlights the importance of stringent evaluations and adjustment of physiological conditions.
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| 28. |
- Klingvall Ek, Rebecca, 1985-
(författare)
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Electron beam melting: Impact of part surface properties on metal fatigue and bone ingrowth
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- AbstractThe aim of this thesis is to investigate aspects on how additive manufacturing (AM) contributes to functional bone implants with the use of the electron beam melting (EBM) technology. AM manufactures parts according to computer-aided design, and the EBM technology melts powder using an electron beam, which acts similar to a laser beam. The topics discussed in this thesis are related to surface roughness that originate from the melted metal powder, and the thesis tries to define some aspects that affect implant functionality. Process parameters steering the electron beam and biocompatibility arising from the surface texture were the initial parts of the PhD studies, and the other half focused on post-processing and fatigue, which are important for medical and industrial applications. There are six studies in this compilation thesis. They are abbreviated as P - process parameters, M - medical applications, and F - fatigue. Studies P, M2, F2, and F3 are journal articles, and M1 and F1 are conference proceedings.Study P used design of experiments to investigate how process parameters affect the surface roughness of as-built EBM-manufactured parts and concluded that beam speed and energy (current) were the most important parameters that influence the surface roughness.In studies M1 and M2, EBM-manufactured specimens of cobalt-chromium and titanium alloys were used to evaluate biocompatibility. The blood chamber method quantified the reactions of the human whole blood in contact with the metal surfaces, and the results showed how the as-built EBM surface roughness contributed to coagulation and bone healing.Rotating beam fatigue equipment was used in studies F1–F3 and study F1 discussed the size effect on fatigue loaded as-built specimens and included specimens with different sizes and with or without hot isostatic pressing (HIP). Study F2 compared as-built and machined specimens and study F3 investigated how Hirtisation, which is a patented electrochemical surface treatment, and HIP affect the fatigue properties that originate from the electrochemical polishing surface topography. The studies showed that a decreased surface roughness increased the fatigue resistance while the stress concentrations (Kt) in the surface of EBM-manufactured specimens decreased.The thesis concludes that EBM-manufactured as-built surfaces are suitable for direct contact with the bone, and that HIP does not improve the fatigue resistance of parts with as-built surfaces, where crack initiation starts at notches.
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| 29. |
- Klingvall Ek, Rebecca, 1985-, et al.
(författare)
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Micro- to Macroroughness of Additively Manufactured Titanium Implants in Terms of Coagulation and Contact Activation
- 2017
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Ingår i: International Journal of Oral & Maxillofacial Implants. - : Quintessence Publishing. - 0882-2786 .- 1942-4434. ; 32:3, s. 565-574
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: This study aimed to evaluate how as-built electron beam melting (EBM) surface properties affect the onset of blood coagulation. The properties of EBM-manufactured implant surfaces for placement have, until now, remained largely unexplored in literature. Implants with conventional designs and custom-made implants have been manufactured using EBM technology and later placed into the human body. Many of the conventional implants used today, such as dental implants, display modified surfaces to optimize bone ingrowth, whereas custom-made implants, by and large, have machined surfaces. However, titanium in itself demonstrates good material properties for the purpose of bone ingrowth. Materials and Methods: Specimens manufactured using EBM were selected according to their surface roughness and process parameters. EBM-produced specimens, conventional machined titanium surfaces, as well as PVC surfaces for control were evaluated using the slide chamber model. Results: A significant increase in activation was found, in all factors evaluated, between the machined samples and EBM-manufactured samples. The results show that EBM-manufactured implants with as-built surfaces augment the thrombogenic properties. Conclusion: EBM that uses Ti6Al4V powder appears to be a good manufacturing solution for load-bearing implants with bone anchorage. The as-built surfaces can be used "as is" for direct bone contact, although any surface treatment available for conventional implants can be performed on EBM-manufactured implants with a conventional design.
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| 30. |
- Klingvall Ek, Rebecca, 1985-
(författare)
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SURFACE PROPERTIES OF IMPLANTS MANUFACTURED USING ELECTRON BEAM MELTING
- 2016
-
Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis summarizes the results concerning the manufacture of medical implants for bone replacement using electron beam melting (EBM) which is an additive manufacturing (AM) technology, and aims to satisfy the engineering needs for the medical functionality of manufacturing technology. This thesis has focused on some microscopic properties for surfaces and bone integration. The process parameters of EBM manufacturing were studied to ascertain whether they have impacts on surface appearance, as surface properties have impacts on bone integration and implant performance.EBM manufacturing uses an electron beam to melt metal powder onto each layer in a manner akin to welding. The electron beam is controlled by process parameters that may be altered to a certain extent by the operator. There are individual process parameters for every material, and new parameters are set when developing new materials. In this thesis, process parameters in default settings were altered to ascertain whether it was possible to specify process parameters for implant manufacturing. The blood chamber model was used for thromboinflammation validation, using human whole blood. The model is used to identify early reactions of coagulation and immunoreactions. The material used in this study was Ti6Al4V-ELI, which is corrosion resistant and has the same surface oxide layers as titanium, and CoCr-F75, which has high stiffness, is wear-resistant and is commonly used in articulating joints.The study shows that among the process parameters researched, a combination of speed and current have the most impact on surface roughness and an interaction of parameters were found using design of experiment (DOE). As-built EBM surfaces show thrombogenicity, which in previous studies has been associated with bone ingrowth.Surface structure of as-build EBM manufactured surfaces are similar to implants surfaces described by Pilliar (2005), but with superior material properties than those of implants with sintered metals beads. By altering the process parameters controlling the electron beam, surface roughness of as-build parts may be affected, and the rougher EBM manufactured surfaces tend to be more thrombogen than the finer EBM manufactured surfaces. As-build EBM manufactured surfaces in general show more thrombogenicity than conventional machined implants surfaces.
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| 31. |
- Lopes, Viviana, et al.
(författare)
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Human Whole Blood Interactions with Craniomaxillofacial Reconstruction Materials : Exploring In Vitro the Role of Blood Cascades and Leukocytes in Early Healing Events
- 2023
-
Ingår i: Journal of Functional Biomaterials. - : MDPI AG. - 2079-4983. ; 14:7
-
Tidskriftsartikel (refereegranskat)abstract
- The present study investigated early interactions between three alloplastic materials (calcium phosphate (CaP), titanium alloy (Ti), and polyetheretherketone (PEEK) with human whole blood using an established in vitro slide chamber model. After 60 min of contact with blood, coagulation (thrombin-antithrombin complexes, TAT) was initiated on all test materials (Ti > PEEK > CaP), with a significant increase only for Ti. All materials showed increased contact activation, with the KK-AT complex significantly increasing for CaP (p < 0.001), Ti (p < 0.01), and PEEK (p < 0.01) while only CaP demonstrated a notable rise in KK-C1INH production (p < 0.01). The complement system had significant activation across all materials, with CaP (p < 0.0001, p < 0.0001) generating the most pronounced levels of C3a and sC5b-9, followed by Ti (p < 0.001, p < 0.001) and lastly, PEEK (p < 0.001, p < 0.01). This activation correlated with leukocyte stimulation, particularly myeloperoxidase release. Consequently, the complement system may assume a more significant role in the early stages post implantation in response to CaP materials than previously recognized. Activation of the complement system and the inevitable activation of leukocytes might provide a more favorable environment for tissue remodeling and repair than has been traditionally acknowledged. While these findings are limited to the early blood response, complement and leukocyte activation suggest improved healing outcomes, which may impact long-term clinical outcomes.
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| 32. |
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| 33. |
- Nederberg, Fredrik, et al.
(författare)
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Phosphoryl Choline Introduces Dual Activity in Biomimetic Ionomers
- 2004
-
Ingår i: Journal of the American Chemical Society. ; :126, s. 15350-15351
-
Tidskriftsartikel (refereegranskat)abstract
- Dual activity of phosphoryl choline (PC) functional poly(trimethylenecarbonate) (PTMC) was found which induces the zwitterionic biomimetic PC group to form physical cross-links with ionomers in the bulk, and at the same time enrich at the surface of cast films. The formation of zwitterionic domains from a bifunctional PC-PTMC-PC (ionomer) provided firm films with a low elastic modulus in contrast to the tacky PTMC starting material (Mn 3900 g/mol) with poor mechanical performance. In addition, the ionomer possessed improved hemocompatible properties that was explained by the enrichment of PC at the surface, suggesting a way to tailor the mechanical performance of biodegradable PTMC-based ionomers while providing its bioactivity. Tailored elasticity while maintaining hemocompatibility of a biodegradable ionomer should be of particular interest for a variety of in vivo applications.
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| 34. |
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| 35. |
- Nilsson, Bo, et al.
(författare)
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Compstatin inhibits complement and cellular activation in whole blood in two models of extracorporeal circulation
- 1998
-
Ingår i: Blood. - 0006-4971 .- 1528-0020. ; 92:5, s. 1661-1667
-
Tidskriftsartikel (refereegranskat)abstract
- Recently, a C3-binding cyclic synthetic peptide (Compstatin) has been identified that binds to complement component C3 and inhibits complement activation. Here we have examined the influence of Compstatin on complement activation and its indirect effects on cellular responses in whole blood in two models for extracorporeal circulation. Compstatin effectively inhibited the generation of C3a and sC5b-9 and the binding of C3/ C3 fragments to the polymer surface. As a result of the inhibition of complement activation, the activation of polymorphonuclear leukocytes (PMNs; as assessed by the expression of CD11b) and the binding of these cells (CD16(+)) to the polymer surface were almost completely lost. In contrast, blood cell counts were not affected. Using surface plasmon resonance technology, we have confirmed that Compstatin exerts its inhibitory effect on complement activation by binding to native C3. These data show that complement activation, leading to activation and binding of PMNs to the biomaterial surface, can be abolished by the addition of Compstatin. The properties of Compstatin make Compstatin a promising drug for use in extracorporeal circuits to avoid bioincompatibility reactions, eg, during cardiopulmonary bypass, but also a favorable precursor peptide for the development of an anticomplement drug for oral use.
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| 36. |
- Nilsson Ekdahl, Kristina, et al.
(författare)
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Contact (kallikrein/kinin) system activation in whole human blood induced by low concentrations of α-Fe2O3 nanoparticles
- 2018
-
Ingår i: Nanomedicine. - : Elsevier. - 1549-9634 .- 1549-9642. ; 14:3, s. 735-744
-
Tidskriftsartikel (refereegranskat)abstract
- Iron-oxide nanoparticles (NPs) generated by environmental events are likely to represent health problems. α-Fe2O3 NPs were synthesized, characterized and tested in a model for toxicity utilizing human whole blood without added anticoagulant. MALDI-TOF of the corona was performed and activation markers for plasma cascade systems (complement, contact and coagulation systems), platelet consumption and release of growth factors, MPO, and chemokine/cytokines from blood cells were analyzed. The coronas formed on the pristine α-Fe2O3 NPs contained contact system proteins and they induced massive activation of the contact (kinin/kallikrein) system, as well as thrombin generation, platelet activation, and release of two pro-angiogeneic growth factors: platelet-derived growth factor and vascular endothelial growth factor, whereas complement activation was unaffected. The α-Fe2O3 NPs exhibited a noticeable toxicity, with kinin/kallikreinactivation, which may be associated with hypotension and long-term angiogenesis in vivo, with implications for cancer, arteriosclerosis and pulmonary disease.
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| 37. |
- Nilsson Ekdahl, Kristina, et al.
(författare)
-
Dangerous liaisons : complement, coagulation, and kallikrein/kinin cross-talk act as a linchpin in the events leading to thromboinflammation
- 2016
-
Ingår i: Immunological Reviews. - : Wiley. - 0105-2896 .- 1600-065X. ; 274:1, s. 245-269
-
Forskningsöversikt (refereegranskat)abstract
- Innate immunity is fundamental to our defense against microorganisms. Physiologically, the intravascular innate immune system acts as a purging system that identifies and removes foreign substances leading to thromboinflammatory responses, tissue remodeling, and repair. It is also a key contributor to the adverse effects observed in many diseases and therapies involving biomaterials and therapeutic cells/organs. The intravascular innate immune system consists of the cascade systems of the blood (the complement, contact, coagulation, and fibrinolytic systems), the blood cells (polymorphonuclear cells, monocytes, platelets), and the endothelial cell lining of the vessels. Activation of the intravascular innate immune system in vivo leads to thromboinflammation that can be activated by several of the system's pathways and that initiates repair after tissue damage and leads to adverse reactions in several disorders and treatment modalities. In this review, we summarize the current knowledge in the field and discuss the obstacles that exist in order to study the cross-talk between the components of the intravascular innate immune system. These include the use of purified in vitro systems, animal models and various types of anticoagulants. In order to avoid some of these obstacles we have developed specialized human whole blood models that allow investigation of the cross-talk between the various cascade systems and the blood cells. We in particular stress that platelets are involved in these interactions and that the lectin pathway of the complement system is an emerging part of innate immunity that interacts with the contact/coagulation system. Understanding the resulting thromboinflammation will allow development of new therapeutic modalities.
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| 38. |
- Nilsson Ekdahl, Kristina, et al.
(författare)
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Evaluation of the blood compatibility of materials, cells and tissues: Basic concepts, test models and practical guidelines
- 2013
-
Ingår i: Complement Therapeutics. - Boston, MA : Springer. - 9781461441175 - 9781461441182 ; 735, s. 257-270
-
Bokkapitel (refereegranskat)abstract
- Medicine today uses a wide range of biomaterials, most of which make contact with blood permanently or transiently upon implantation. Contact between blood and nonbiological materials or cells or tissue of nonhematologic origin initiates activation of the cascade systems (complement, contact activation/coagulation) of the blood, which induces platelet and leukocyte activation.Although substantial progress regarding biocompatibility has been made, many materials and medical treatment procedures are still associated with severe side effects. Therefore, there is a great need for adequate models and guidelines for evaluating the blood compatibility of biomaterials. Due to the substantial amount of cross talk between the different cascade systems and cell populations in the blood, it is advisable to use an intact system for evaluation.Here, we describe three such in vitro models for the evaluation of the biocompatibility of materials and therapeutic cells and tissues. The use of different anticoagulants and specific inhibitors in order to be able to dissect interactions between the different cascade systems and cells of the blood is discussed. In addition, we describe two clinically relevant medical treatment modalities, the integration of titanium implants and transplantation of islets of Langerhans to patients with type 1 diabetes, whose mechanisms of action we have addressed using these in vitro models.
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| 39. |
- Nilsson, Per H., et al.
(författare)
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Autoregulation of thromboinflammation on biomaterial surfaces by a multicomponent therapeutic coating
- 2013
-
Ingår i: Biomaterials. - : Elsevier BV. - 0142-9612 .- 1878-5905. ; 34:4, s. 985-994
-
Tidskriftsartikel (refereegranskat)abstract
- Activation of the thrombotic and complement systems is the main recognition and effector mechanisms in the multiple adverse biological responses triggered when biomaterials or therapeutic cells come into blood contact. We have created a surface which is auto-protective to human innate immunity by combining three fundamentally different strategies, all developed by us previously, which have been shown to induce substantial, but incomplete hemocompatibility when used separately. In summary, we have conjugated a factor H-binding peptide; and an ADP-degrading enzyme; using a PEG linker on both material and cellular surfaces. When exposed to human whole blood, factor H was specifically recruited to the modified surfaces and inhibited complement attack. In addition, activation of platelets and coagulation was efficiently attenuated, by degrading ADP. Thus, by inhibiting thromboinflammation using a multicomponent approach, we have created a hybrid surface with the potential to greatly reduce incompatibility reactions involving biomaterials and transplantation.
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| 40. |
- Nordling, Sofia, et al.
(författare)
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Vascular repair utilising immobilised heparin conjugate for protection against early activation of inflammation and coagulation
- 2015
-
Ingår i: Thrombosis and Haemostasis. - 0340-6245 .- 2567-689X. ; 113:6, s. 1312-1322
-
Tidskriftsartikel (refereegranskat)abstract
- Ischaemia-reperfusion injury (IRI) poses a major challenge in many thrombotic conditions and in whole organ transplantation. Activation of the endothelial cells and shedding of the protective vascular glycocalyx during IRI increase the risk of innate immune activation, cell infiltration and severe thrombus formation, promoting damage to the tissue. Here, we present a novel one-step strategy to protect the vas, culature by immobilisation of a unique multi-arm heparin conjugate to the endothelium. Applying a new in vitro blood endothelial cell chamber model, the heparin conjugate was found to bind not only to primary human endothelial cells but also directly to the collagen to which the cells adhered. Incubation of hypoxic endothelial cells with freshly drawn human blood in the blood chambers elicited coagulation activation reflected by thrombin anti-thrombin formation and binding of platelets and neutrophils. Immobilisation of the heparin conjugate to the hypoxic endothelial cells created a protective coating, leading to a Significant reduction of the recruitment of blood cells and coagulation activation compared to untreated hypoxic endothelial cells. This novel approach of immobilising multi-arm heparin conjugates on the endothelial cells and collagen of the basement membrane ensures to protect the endothelium against IRI in thrombotic disorders and in transplantation.
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| 41. |
- Rocha, Igor, et al.
(författare)
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Blood Compatibility of Sulfonated Cladophora Nanocellulose Beads
- 2018
-
Ingår i: Molecules. - : MDPI AG. - 1431-5157 .- 1420-3049. ; 23:3
-
Tidskriftsartikel (refereegranskat)abstract
- Sulfonated cellulose beads were prepared by oxidation of Cladophora nanocellulose to 2,3-dialdehyde cellulose followed by sulfonation using bisulfite. The physicochemical properties of the sulfonated beads, i.e., high surface area, high degree of oxidation, spherical shape, and the possibility of tailoring the porosity, make them interesting candidates for the development of immunosorbent platforms, including their application in extracorporeal blood treatments. A desired property for materials used in such applications is blood compatibility; therefore in the present work, we investigate the hemocompatibility of the sulfonated cellulose beads using an in vitro whole blood model. Complement system activation (C3a and sC5b-9 levels), coagulation activation (thrombin-antithrombin (TAT) levels) and hemolysis were evaluated after whole blood contact with the sulfonated beads and the results were compared with the values obtained with the unmodified Cladophora nanocellulose. Results showed that neither of the cellulosic materials presented hemolytic activity. A marked decrease in TAT levels was observed after blood contact with the sulfonated beads, compared with Cladophora nanocellulose. However, the chemical modification did not promote an improvement in Cladophora nanocellulose hemocompatibility in terms of complement system activation. Even though the sulfonated beads presented a significant reduction in pro-coagulant activity compared with the unmodified material, further modification strategies need to be investigated to control the complement activation by the cellulosic materials.
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| 42. |
- Sellberg, Felix, et al.
(författare)
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Polyvinylalcohol-carbazate (PVAC) reduces red blood cell hemolysis
- 2019
-
Ingår i: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 14:12
-
Tidskriftsartikel (refereegranskat)abstract
- Background and objectives: The objective of this study was to investigate whether a soluble polymer and aldehyde-scavenger, polyvinylalcohol-carbazate (PVAC), can inhibit hemolysis in the storage of red blood cells (RBC).Study design and methods: The effect of PVAC was assessed over a wide range of concentrations, using absorption spectroscopy to evaluate the level of hemolysis. Moreover, osmotic stability and aldehyde-scavenging potential of RBC were assessed after storage in PVAC.Results: After test tube storage for two weeks, red blood cell hemolysis was lower with PVAC compared to controls (mean difference 23%, 95% CI 16-29%, p < 0.001). A higher level of hemolysis led to a pronounced effect with PVAC. RBC stored in PVAC improved both the binding of free aldehydes (p <0.001) and the osmotic stability (p = 0.0036).Conclusion: Erythrocytes stored with PVAC showed less hemolysis, which might be explained by the ability of PVACs to stabilize the cell membrane and decrease oxidative injury.
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| 43. |
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| 44. |
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| 45. |
- Thor, Andreas Li, et al.
(författare)
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Correlation of Platelet Growth Factor Release in Jawbone Defect Repair - A Study in the Dog Mandible.
- 2013
-
Ingår i: Clinical implant dentistry and related research. - : Wiley. - 1708-8208 .- 1523-0899. ; 15:5, s. 759-768
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Platelet concentrate/platelet-rich plasma (PRP) has been studied extensively in various experimental models and there is some agreement among workers to its early effect in bone regeneration and healing. We have earlier showed in vitro that titanium in whole blood activates the thrombogenic response to a higher degree than PRP and that a fluoridated test surface augmented the effect compared with control. Purpose: We designed this study to evaluate the effect of PRP and whole blood on bone regeneration in a dog implant defect model and, in addition, the effect of a test surface modified in hydrofluoric acid. A correlation attempt between platelet count, release of growth factors, and bone regeneration was made. Materials and Methods: Six dogs were used and simultaneously with the experimental surgery and implant installation, autologous PRP was prepared. Defects were prepared (6mm in diameter and 5mm deep), and implants were installed (TiO(2) gritblasted and hydrofluoric acid treated [test] or TiO(2) gritblasted [control], 5mm in diameter and 9mm long) in defects filled with either PRP or whole blood. Randomization of sides between PRP and whole blood, and sites for test and control implants were made. Blood samples were collected from PRP and whole blood. The dogs were killed after 5 weeks of healing, and samples with implants and surrounding bone were collected and processed for analysis. Enzyme linked immunosorbent assays were used for detection of growth factors in PRP. Results: The mean increase of platelet count was 424% in PRP. A correlation for platelet counts and transforming growth factor β was found in each dog (r(2) =0.857). Approximately 50% of the region of interest (ROI) in the defects was filled with new bone after 5 weeks. No difference could be observed in ROI by using PRP or whole blood in the defects regarding new bone formation, bone in contact with implant, or distance to first bone contact. However, the fluoridated implants exhibited more new bone formation (p=.03) compared with control, regardless of comparing PRP or whole blood, and also displayed a shorter distance from first bone contact to the margin of the bone envelope (p=.05). Conclusions: Platelet concentrate/PRP failed to show more new bone regeneration in a peri-implant defect model compared with whole blood. Implants treated with hydrofluoric acid displayed higher percentages of bone fill in the defect.
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| 46. |
- Thor, Andreas, et al.
(författare)
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The role of whole blood in thrombin generation in contact with various titanium surfaces
- 2007
-
Ingår i: Biomaterials. - : Elsevier BV. - 0142-9612 .- 1878-5905. ; 28:6, s. 966-74
-
Tidskriftsartikel (refereegranskat)abstract
- Understanding of the thrombotic response (activation of the intrinsic coagulation system followed by platelet activation) from blood components upon contact with a titanium dental implant is important and not fully understood. The aims of this study were to evaluate: (1) the thrombogenic response of whole blood, platelet-rich plasma (PRP) and platelet-poor plasma (PPP) in contact with a highly thrombogenic surface as titanium, (2) the thrombogenic response of clinically used surfaces as hydroxyapatite (HA), machined titanium (mTi), TiO2 grit-blasted titanium (TiOB) and fluoride ion-modified grit-blasted titanium (TiOB-F). An in vitro slide chamber model, furnished with heparin, was used in which whole blood, PRP or PPP came in contact with slides of the test surfaces. After incubation (60 min rotation at 22 rpm in a 37 degrees C water bath), blood/plasma was mixed with EDTA or citrate, further centrifuged at +4 degrees C (2200 g at 10 min). Finally, plasma was collected pending analysis. Whole blood in contact with Ti alloy resulted in the binding of platelets to the material surface and in the generation of thrombin-antithrombin (TAT) complexes. With whole blood TAT levels increased 1000-fold compared with PRP and PPP, in which both almost no increase of TAT could be detected. In addition, the platelet activation showed a similar pattern with a 15-fold higher release of beta-TG in whole blood. In the in vitro chamber model with the clinically relevant materials, the fluoride-modified surface (TiOB-F) showed pronounced TAT generation compared with TiOB, mTi and HA. Similar results were achieved for platelet consumption and activation markers of the intrinsic coagulation system. Taken together these results implicate first that whole blood is necessary for sufficient thrombin generation and platelet activation during placement of implants. Second, a fluoride ion modification seems to augment the thrombogenic properties of titanium.
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| 47. |
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