| 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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