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Janson, O., Gururaj, S., Pujari-Palmer, S., Karlsson Ott, M., Strømme, M., Engqvist, H. & Welch, K. (2019). Titanium surface modification to enhance antibacterial and bioactive properties while retaining biocompatibility. Materials science & engineering. C, biomimetic materials, sensors and systems, 96, 272-279
Öppna denna publikation i ny flik eller fönster >>Titanium surface modification to enhance antibacterial and bioactive properties while retaining biocompatibility
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2019 (Engelska)Ingår i: Materials science & engineering. C, biomimetic materials, sensors and systems, ISSN 0928-4931, E-ISSN 1873-0191, Vol. 96, s. 272-279Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Bacterial infections associated with metal implants are severe problems affecting a considerable amount of people with dental or orthopedic implants. This study aims to examine the antibacterial effect of a Titanium-peroxy gel layer on the modified surface of commercially pure titanium grade 2. Variations in a multi-step surface modification procedure were tested to determine the best combination that provided an antibacterial effect while enhancing bioactivity without compromising biocompatibility. Soaking the surfaces in 30 wt% hydrogen peroxide held at 80 °C provided antibacterial activity while subsequent surface treatments in concentrated sodium and calcium hydroxide solutions were preformed to enhance bioactivity. Staphylococcus epidermidis was used to determine the antibacterial effect through both direct contact and biofilm inhibition tests while human dermal fibroblast cells and MC3T3 pre osteoblast cells were utilized to test biocompatibility. The greatest antibacterial effect was observed with only hydrogen peroxide treatment, but the resulting surface was neither bioactive nor biocompatible. It was found that subsequent surface treatments with sodium hydroxide followed by calcium hydroxide provided a bioactive surface that was also biocompatible. Additionally, a final treatment with autoclaving showed positive effects with regards to enhanced bioactivity. This multi-step surface modification procedure offers a promising, non-antibiotic, solution for combatting infections associated with biomedical implants.

Nyckelord
Titanium, Antibacterial, Bioactivity, Cell viability, Sodium titanate, Calcium titanate
Nationell ämneskategori
Materialteknik
Identifikatorer
urn:nbn:se:uu:diva-358023 (URN)10.1016/j.msec.2018.11.021 (DOI)000456760700027 ()30606532 (PubMedID)
Forskningsfinansiär
Vinnova
Tillgänglig från: 2018-08-23 Skapad: 2018-08-23 Senast uppdaterad: 2019-03-15Bibliografiskt granskad
Pujari-Palmer, S., Lu, X., Singh, V. P., Engman, L., Pujari-Palmer, M. & Karlsson Ott, M. (2017). Incorporation and delivery of an organoselenium antioxidant from a brushite cement. Materials letters (General ed.), 197, 115-119
Öppna denna publikation i ny flik eller fönster >>Incorporation and delivery of an organoselenium antioxidant from a brushite cement
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2017 (Engelska)Ingår i: Materials letters (General ed.), ISSN 0167-577X, E-ISSN 1873-4979, Vol. 197, s. 115-119Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

An inflammatory reaction occurs following biomaterial implantation in the body, which produce toxic byproducts such as reactive oxygen species (ROS). Although ROS is required to clear the wound, excessive ROS can damage the tissue around the implant site, eventually leading to implant failure. One approach to control the inflammatory response is to incorporate an antioxidant into the biomaterial in order to scavenge ROS produced by activated phagocytes. In the present study, an organoselenium antioxidative compound was incorporated into a brushite cement, with the goal of scavenging ROS generated from activated primary human mononuclear leukocytes (MNCs), in vitro. The effect of the antioxidant on the physical properties of brushite cement, and its release from the cement were investigated via compressive strength, setting time, phase composition, and UV spectroscopy analysis. The physical properties of brushite remained unchanged following incorporation of the antioxidant. The antioxidant was slowly released from the cement, following a non-Fickian transport mechanism, with approximately 60% of the loaded antioxidant released over five days. The released antioxidant was then tested for its ability to scavenge ROS released by MNCs using the luminol amplified chemiluminescence assay. The results show that antioxidative released at both early stages (24 h) and late stages (120 h) retained its scavenging capacity and effectively reduced ROS production. These results indicate that brushite cements loaded with organoselenium compounds can modulate ROS production after implantation and potentially modulate the inflammatory response to improve device integration.

Nyckelord
Antioxidants, Reactive oxygen species, Calcium phosphate cements, Inflammation, Biomaterial, Drug delivery
Nationell ämneskategori
Materialteknik
Identifikatorer
urn:nbn:se:uu:diva-322444 (URN)10.1016/j.matlet.2017.03.139 (DOI)000399500300031 ()
Forskningsfinansiär
Carl Tryggers stiftelse för vetenskaplig forskning , CTS 13:346Magnus Bergvalls Stiftelse, 2015-01111Stiftelsen Längmanska kulturfonden, 16-2-41
Tillgänglig från: 2017-05-23 Skapad: 2017-05-23 Senast uppdaterad: 2017-05-23Bibliografiskt granskad
Singh, V. P., Poon, J.-f., Yan, J., Lu, X., Karlsson Ott, M., Butcher, R. J., . . . Engman, L. (2017). Nitro-, Azo-, and Amino Derivatives of Ebselen: Synthesis, Structure, and Cytoprotective Effects. Journal of Organic Chemistry, 82(1), 313-321
Öppna denna publikation i ny flik eller fönster >>Nitro-, Azo-, and Amino Derivatives of Ebselen: Synthesis, Structure, and Cytoprotective Effects
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2017 (Engelska)Ingår i: Journal of Organic Chemistry, ISSN 0022-3263, E-ISSN 1520-6904, Vol. 82, nr 1, s. 313-321Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Novel azo-bis-ebselen compounds 7 were prepared by reduction of 7-nitro-2-aryl-1,2-benzisoselenazol-3(2H)ones 3 and 6 with sodium benzenetellurolate; NaTeC6H5, and by reaction of 2-bromo-3-nitrobenzamides with Na2Se2. The X-ray structure of 7b showed that the molecule, due to strong intramolecular secondary Se center dot center dot center dot N interactions, is completely planar. Azo-compounds 7 upon further reaction with NaTeC6H5 were reductively cleaved to provide 2 equiv of the corresponding aromatic amine. The weak Se-N bond was not stable enough to survive the reaction conditions, and diselenides 8 were isolated after workup. Whereas azo-bis-ebselens 7 were poor mimics of the glutathione peroxidase (GPx)-enzymes, nitroebselens 3, 6, and 11b and diselenides 8 were 3-6-fold more active than ebselen. Based on Se-77 NMR. spectroscopy, a catalytic cycle for diselenide 8b, involving aminoebselen 14, was proposed. As assessed by chemiluminescence measurements, the good GPx-mimics could reduce production of reactive oxygen species (ROS) in stimulated human mononuclear cells more efficiently than Trolox. No toxic effects of the, compounds were seen in MC3T3-cells at 25 mu M.

Nationell ämneskategori
Organisk kemi Teknik och teknologier
Identifikatorer
urn:nbn:se:uu:diva-312514 (URN)10.1021/acs.joc.6b02418 (DOI)000391781900030 ()27966348 (PubMedID)
Forskningsfinansiär
ÅForsk (Ångpanneföreningens Forskningsstiftelse), 16-364Stiftelsen Olle Engkvist Byggmästare, 2016/159Carl Tryggers stiftelse för vetenskaplig forskning , CTS 13:346
Tillgänglig från: 2017-01-10 Skapad: 2017-01-10 Senast uppdaterad: 2017-11-29Bibliografiskt granskad
Kovacs, D., Lu, X., Meszaros, L. S., Ott, M., Andres, J. & Borbas, K. E. (2017). Photophysics of Coumarin and Carbostyril-Sensitized Luminescent Lanthanide Complexes: Implications for Complex Design in Multiplex Detection. Journal of the American Chemical Society, 139(16), 5756-5767
Öppna denna publikation i ny flik eller fönster >>Photophysics of Coumarin and Carbostyril-Sensitized Luminescent Lanthanide Complexes: Implications for Complex Design in Multiplex Detection
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2017 (Engelska)Ingår i: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 139, nr 16, s. 5756-5767Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Luminescent lanthanide (Ln(III)) complexes with coumarin or carbostyril antennae were synthesized and their photophysical properties evaluated using steady-state and time-resolved UV-vis spectroscopy. Ligands bearing distant hydroxycoumarin-derived antennae attached through triazole linkers were modest sensitizers for Eu(III) and Tb(III), whereas ligands with 7-amidocarbostyrils directly linked to the coordination site could reach good quantum yields for multiple Ln(III), including the visible emitters Sm(III) and Dy(III), and the near-infrared emitters Nd(III) and Yb(III). The highest lanthanide-centered luminescence quantum yields were 35% (Tb), 7.9% (Eu), 0.67% (Dy), and 0.18% (Sm). Antennae providing similar luminescence intensities with 2-4 Ln-emitters were identified. Photoredox quenching of the carbostyril antenna excited states was observed for all Eu(III)-complexes and should be sensitizing in the case of Yb(III); the scope of the process extends to Ln(III) for which it has not been seen previously, specifically Dy(III) and Sm(III). The proposed process is supported by photophysical and electrochemical data. A FRET-type mechanism was identified in architectures with both distant and close antennae for all of the Lns. This mechanism seems to be the only sensitizing one at long distance and probably contributes to the sensitization at shorter distances along with the triplet pathway. The complexes were nontoxic to either bacterial or mammalian cells. Complexes of an ester-functionalized ligand were taken up by bacteria in a concentration-dependent manner. Our results suggest that the effects of FRET and photoredox quenching should be taken into consideration when designing luminescent Ln complexes. These results also establish these Ln(III)-complexes for multiplex detection beyond the available two-color systems.

Ort, förlag, år, upplaga, sidor
AMER CHEMICAL SOC, 2017
Nationell ämneskategori
Kemi Teknik och teknologier
Identifikatorer
urn:nbn:se:uu:diva-322722 (URN)10.1021/jacs.6b11274 (DOI)000400321500029 ()28388066 (PubMedID)
Forskningsfinansiär
Vetenskapsrådet, 2013-4655Stiftelsen Olle Engkvist Byggmästare
Tillgänglig från: 2017-05-29 Skapad: 2017-05-29 Senast uppdaterad: 2019-04-16Bibliografiskt granskad
Lu, X., Mestres, G., Singh, V. P., Effati, P., Poon, J.-F., Engman, L. & Marjam, K. O. (2017). Selenium- and tellurium-based antioxidants for modulating inflammation and effects on osteoblastic activity. Antioxidants, 6(13), 1-13
Öppna denna publikation i ny flik eller fönster >>Selenium- and tellurium-based antioxidants for modulating inflammation and effects on osteoblastic activity
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2017 (Engelska)Ingår i: Antioxidants, E-ISSN 2076-3921, Vol. 6, nr 13, s. 1-13Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Increased oxidative stress plays a significant role in the etiology of bone diseases. Heightened levels of H2O2 disrupt bone homeostasis, leading to greater bone resorption than bone formation. Organochalcogen compounds could act as free radical trapping agents or glutathione peroxidase mimetics, reducing oxidative stress in inflammatory diseases. In this report, we synthesized and screened a library of organoselenium and organotellurium compounds for hydrogen peroxide scavenging activity, using macrophagic cell lines RAW264.7 and THP-1, as well as human mono- and poly-nuclear cells. These cells were stimulated to release H2O2, using phorbol 12-myristate 13-acetate, with and without organochalogens. Released H2O2 was then measured using a chemiluminescent assay over a period of 2 h. The screening identified an organoselenium compound which scavenged H2O2 more effectively than the vitamin E analog, Trolox. We also found that this organoselenium compound protected MC3T3 cells against H2O2 -induced toxicity, whereas Trolox did not. The organoselenium compound exhibited no cytotoxicity to the cells and had no deleterious effects on cell proliferation, viability, or alkaline phosphatase activity. The rapidity of H2O2 scavenging and protection suggests that the mechanism of protection is due to the direct scavenging of extracellular H2O2. This compound is a promising modulators of inflammation and could potentially treat diseases involving high levels of oxidative stress.

Nyckelord
antioxidants, reactive oxygen species, inflammation
Nationell ämneskategori
Immunologi Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci) Teknik och teknologier
Identifikatorer
urn:nbn:se:uu:diva-315564 (URN)10.3390/antiox6010013 (DOI)000398677900012 ()
Tillgänglig från: 2017-02-15 Skapad: 2017-02-15 Senast uppdaterad: 2017-05-18Bibliografiskt granskad
Pujari-Palmer, S., Lu, X. & Karlsson Ott, M. (2017). The Influence of Hydroxyapatite Nanoparticle Morphology on Embryonic Development in a Zebrafish Exposure Model. NANOMATERIALS, 7(4), Article ID 89.
Öppna denna publikation i ny flik eller fönster >>The Influence of Hydroxyapatite Nanoparticle Morphology on Embryonic Development in a Zebrafish Exposure Model
2017 (Engelska)Ingår i: NANOMATERIALS, ISSN 2079-4991, Vol. 7, nr 4, artikel-id 89Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Nanomaterials are used in many different industries such as cosmetics, food, clothing, and electronics. There is increasing concern that exposure to nanoparticles (NPs) during pregnancy can adversely affect fetal development. It is well known that the size, charge, and chemistry of a nanoparticle can modulate embryological development. The role that particle morphology plays on early development, however, is still widely unknown. The present study aims to investigate the effect of hydroxyapatite nanoparticle (HANP) morphology on embryological development in a zebrafish exposure model. Four distinct HANP morphologies (dots, long rods, sheets, and fibers) were fabricated and characterized. Zebrafish embryos were exposed to HANPs (0-100 mg/L), and viability and developmental deformities were evaluated for up to 5 days post-fertilization (dpf). Malformations such as pericardial edema and axial curvature were apparent in embryos as early as 1 dpf, following exposure to the dot and fiber particles, and developed in embryos by 3 dpf in the sheet and long rod particle groups. Minimal death was observed in response to dot, long rod, and sheet particles (<= 25%), while fiber particles induced overwhelming toxicity (<= 60%) after 1 dpf, and complete toxicity during all subsequent time points. Collectively, these results suggest that nanoparticle morphology can significantly impact embryological development and should be a required consideration when designing nanomaterials for commercial use.

Nyckelord
nanoparticle morphology, hydroxyapatite, zebrafish development
Nationell ämneskategori
Nanoteknik
Identifikatorer
urn:nbn:se:uu:diva-329136 (URN)10.3390/nano7040089 (DOI)000404048100018 ()
Forskningsfinansiär
Science for Life Laboratory - a national resource center for high-throughput molecular bioscience
Tillgänglig från: 2017-10-10 Skapad: 2017-10-10 Senast uppdaterad: 2017-10-11Bibliografiskt granskad
Mestres, G., Kugiejko, K., Pastorino, D., Unosson, J., Öhman, C., Karlsson Ott, M., . . . Persson, C. (2016). Changes in the drug release pattern of fresh and set simvastatin-loaded brushite cement. Materials science & engineering. C, biomimetic materials, sensors and systems, 58, 88-96
Öppna denna publikation i ny flik eller fönster >>Changes in the drug release pattern of fresh and set simvastatin-loaded brushite cement
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2016 (Engelska)Ingår i: Materials science & engineering. C, biomimetic materials, sensors and systems, ISSN 0928-4931, E-ISSN 1873-0191, Vol. 58, s. 88-96Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Calcium phosphate cements are synthetic bone graft substitutes able to set at physiological conditions.They can be applied by minimally invasive surgery and can also be used as drug delivery systems.Consequently, the drug release pattern from the cement paste (fresh cement) is of high clinical interest.However, previous studies have commonly evaluated the drug release using pre-set cements only.Therefore, the aim of this work was to determine if the time elapsed from cement preparation untilimmersion in the solution (3 min for fresh cements, and 1 h and 15 h for pre-set cements) had aninfluence on its physical properties, and correlating these to the drug release profile. Simvastatin wasselected as a model drug, while brushite cement was used as drug carrier. This study quantified howthe setting of a material reduces the accessibility of the release media to the material, thus preventingdrug release. A shift in the drug release pattern was observed, from a burst-release for fresh cements toa sustained release for pre-set cements.

Nyckelord
Brushite; Calcium phosphate cement; Local drug release; Tortuosity; Simvastatin; Setting
Nationell ämneskategori
Teknik och teknologier
Identifikatorer
urn:nbn:se:uu:diva-260560 (URN)10.1016/j.msec.2015.08.016 (DOI)000364247500011 ()
Forskningsfinansiär
VINNOVA, GROWTH 291795VINNOVA, 2013-01260Stiftelsen för internationalisering av högre utbildning och forskning (STINT), IG2011-2047
Tillgänglig från: 2015-08-20 Skapad: 2015-08-20 Senast uppdaterad: 2017-12-04Bibliografiskt granskad
Hoess, A., López, A., Engqvist, H., Ott, M. & Persson, C. (2016). Comparison of a quasi-dynamic and a static extraction method for the cytotoxic evaluation of acrylic bone cements. Materials science & engineering. C, biomimetic materials, sensors and systems, 62, 274-282
Öppna denna publikation i ny flik eller fönster >>Comparison of a quasi-dynamic and a static extraction method for the cytotoxic evaluation of acrylic bone cements
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2016 (Engelska)Ingår i: Materials science & engineering. C, biomimetic materials, sensors and systems, ISSN 0928-4931, E-ISSN 1873-0191, Vol. 62, s. 274-282Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

In this study, two different extraction approaches were compared in order to evaluate the cytotoxicity of 7 different acrylic bone cements, mainly developed for spinal applications, to osteoblastic cells. Firstly, a static extraction was carried out continuously over 24 h, a method widely used in literature. Secondly, a quasi-dynamic extraction method that allowed the investigation of time-dependent cytotoxic effects of curing acrylic bone cements to cells was introduced. In both cases the extraction of the cements was started at a very early stage of the polymerization process to simulate the conditions during clinical application. Data obtained by the quasi-dynamic extraction method suggest that the cytotoxicity of the setting materials mainly originates from the release of toxic components during the first hour of the polymerization reaction. It was also shown that a static extraction over 24 h generally represents this initial stage of the curing process. Furthermore, compared to the static extraction, time dependent cytotoxicity profiles could be detected using the quasi-dynamic extraction method. Specifically, a modification of commercial Osteopal (R) V with castor oil as a plasticizer as well as a customized cement formulation showed clear differences in cytotoxic behavior compared to the other materials during the setting process. In addition, it was observed that unreacted monomer released from the castor oil modified cement was not the main component affecting the toxicity of the material extracts. The quasi-dynamic extraction method is a useful tool to get deeper insight into the cytotoxic potential of curing acrylic bone cements under relevant biological conditions, allowing systematic optimization of materials under development.

Nyckelord
Bone cement; PMMA; Cytotoxicity; In vitro; Extraction conditions; Cell culture
Nationell ämneskategori
Materialteknik Medicinska material och protesteknik
Forskningsämne
Teknisk fysik med inriktning mot materialvetenskap
Identifikatorer
urn:nbn:se:uu:diva-280836 (URN)10.1016/j.msec.2016.01.048 (DOI)000372759100034 ()
Externt samarbete:
Forskningsfinansiär
VINNOVA, VINNMER 2010-02073
Tillgänglig från: 2016-03-15 Skapad: 2016-03-15 Senast uppdaterad: 2018-02-08Bibliografiskt granskad
Lee, B., Samantha, H., Gemma, M., Marjam, K. O., Philip, K. & Kathryn, G. (2016). Dual-Topography Electric Discharge Machining of Titanium to Improve Biocompatibility. Surface and Coatings Technology, 296, 149-156
Öppna denna publikation i ny flik eller fönster >>Dual-Topography Electric Discharge Machining of Titanium to Improve Biocompatibility
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2016 (Engelska)Ingår i: Surface and Coatings Technology, ISSN 0257-8972, Vol. 296, s. 149-156Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Surface modifications of titanium are widespread in an effort to improve the osseointegration capabilities of the metal for orthopaedic and dental applications. Here, electrical discharge machining (EDM) was used to create modified, notably, dual-topography surfaces on titanium. By swapping conventional copper electrodes for a titanium electrode and water dielectric, modified surfaces free of trace element contaminants were produced. Three surfaces were produced by varying the peak currents at 10 A, 29 A and a uniquely hierarchical multi current combination of 29 A followed by 2.4 A. The physicochemical properties of these surfaces were analyzed by scanning electron microscopy (SEM), Energy Dispersive X-Ray Spectroscopy (EDX), and Auger Spectroscopy. These revealed the topography of the modified surfaces and a titanium oxide layer that was markedly thicker on the EDM samples compared to controls. In vitro cell testing was carried out with osteoblast-like MC3T3-E1 cells. Cell differentiation was increased in all EDM modified surfaces compared to controls and early differentiation was promoted on the dual-topography surface. The present study suggests the promise of dual-topography surfaces created using EDM for implant applications.

Nyckelord
Bone; Electrical discharge machining; Osseointegration; Titanium; Topography
Nationell ämneskategori
Materialteknik
Identifikatorer
urn:nbn:se:uu:diva-283418 (URN)10.1016/j.surfcoat.2016.04.024 (DOI)000379278900019 ()
Tillgänglig från: 2016-04-12 Skapad: 2016-04-12 Senast uppdaterad: 2016-08-02Bibliografiskt granskad
Mestres, G., Espanol, M., Xia, W., Tenje, M. & Ott, M. (2016). Evaluation of Biocompatibility and Release of Reactive Oxygen Species of Aluminum Oxide-Coated Materials. ACS Omega, 1(4), 706-713
Öppna denna publikation i ny flik eller fönster >>Evaluation of Biocompatibility and Release of Reactive Oxygen Species of Aluminum Oxide-Coated Materials
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2016 (Engelska)Ingår i: ACS Omega, ISSN 2470-1343, Vol. 1, nr 4, s. 706-713Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Surface properties of biomaterials can strongly influence biomaterial−host interactions. For this reason, coating processes open a wide range of possibilities to modulate the fate of a biomaterial in the body. This study evaluates the effect of a coating material intended for drug delivery capsules on biocompatibility and the release of reactive oxygen species (ROS), that is, respiratory burst in macrophages that indicates acute inflammation. In parallel with a new approach to develop drug-delivery capsules by directly coating solid-state drug particles, in this study, glass slides and silicon nanoparticles (NPs) were coated with aluminum oxide (Al2O3) using atomic layer deposition. Different sizes of NPs (20 and 310 nm) were suspended at different concentrations (10, 100, and 1000 μg/mL) and were evaluated. The homogeneous coating of slides was proved using X-ray photoelectron spectroscopy, and the coating on NP was observed using transmission electron microscopy. Human dermal fibroblasts and human osteoblasts were able to proliferate on the coated slides and in the presence of a suspension of coated NPs (20 and 310 nm) at a low concentration (10 μg/mL). The macrophages released ROS only when in contact with NPs at a concentration of 1000 μg/mL, where the 20 nm NPs caused a higher release of ROS than the 310 nm NPs. This study shows that Al2O3 coatings do not affect the cells negatively and that the cell viability was compromised only when in contact with a high concentration (1000 μg/mL) of smaller (20 nm) NPs. 

Nationell ämneskategori
Materialteknik
Identifikatorer
urn:nbn:se:uu:diva-307254 (URN)10.1021/acsomega.6b00198 (DOI)000392717300022 ()
Forskningsfinansiär
VINNOVA, GROWTH 291795Forskningsrådet Formas
Tillgänglig från: 2016-11-11 Skapad: 2016-11-11 Senast uppdaterad: 2017-03-06Bibliografiskt granskad
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