| 1. |
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| 2. |
- 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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| 3. |
- 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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| 4. |
- 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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| 5. |
- 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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| 6. |
- 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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| 7. |
- 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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| 8. |
- 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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| 9. |
- 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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| 10. |
- 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
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Ingår i: Complement Therapeutics. - Boston, MA : Springer. - 9781461441175 - 9781461441182 ; 735, s. 257-270
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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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| 11. |
- Nilsson, Per H., et al.
(författare)
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Autoregulation of thromboinflammation on biomaterial surfaces by a multicomponent therapeutic coating
- 2013
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Ingår i: Biomaterials. - : Elsevier BV. - 0142-9612 .- 1878-5905. ; 34:4, s. 985-994
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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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| 12. |
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| 13. |
- 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
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Ingår i: Clinical implant dentistry and related research. - : Wiley. - 1708-8208 .- 1523-0899. ; 15:5, s. 759-768
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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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