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Fowler, L., Janson, O., Engqvist, H., Norgren, S. & Öhman, C. (2019). Antibacterial investigation of titanium-copper alloys using luminescent Staphylococcus epidermidis in a direct contact test. Materials science & engineering. C, biomimetic materials, sensors and systems, 97, 707-714
Open this publication in new window or tab >>Antibacterial investigation of titanium-copper alloys using luminescent Staphylococcus epidermidis in a direct contact test
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2019 (English)In: Materials science & engineering. C, biomimetic materials, sensors and systems, ISSN 0928-4931, E-ISSN 1873-0191, Vol. 97, p. 707-714Article in journal (Refereed) Published
Abstract [en]

Commercially pure titanium (CP-Ti), used as oral implants, is often populated by various bacterial colonies in the oral cavity. These bacteria can cause Peri-implantitis, leading to loss of bone tissue and failure of implants. With the increased awareness of antibiotic resistance, research has been directed towards alternative solutions and recent findings have indicated titanium-copper (Ti-Cu) alloys as a promising antibacterial material. The aim of this study was to produce homogeneous Ti-Cu alloys, with various concentrations of copper, and to characterise their antibacterial properties through direct contact tests, using luminescent bacteria, in addition to traditional materials characterisation techniques. Samples of CP-Ti and four different Ti-Cu alloys (1, 2.5, 3 and 10 wt%Cu) were produced in an arc-furnace, heated treated and rapidly quenched. X-ray diffraction revealed that Ti2Cu, was present only in the 10 wt%Cu alloy, however, scanning electron microscopy (SEM) indicated precipitates at the grain boundaries of the 3 wt%Cu alloy, which were confirmed to be of a copper rich phase by energy dispersive x-ray spectroscopy (EDS) analysis. EDS line scans confirmed that the alloys were homogenous. After 6 h, a trend between copper content and antibacterial rate could be observed, with the 10 wt%Cu alloy having the highest rate. SEM confirmed fewer bacteria on the 3 wt%Cu and especially the 10 wt%Cu samples. Although the 10 wt%Cu alloy gave the best antibacterial results, it is desired that the Cu concentration is below similar to 3 wt%Cu to maintain similar mechanical and corrosive performance as CP-Ti. Therefore, it is proposed that future work focuses on the 3 wt%Cu alloy.

Place, publisher, year, edition, pages
ELSEVIER SCIENCE BV, 2019
Keywords
Copper, Titanium, Antibacterial, S. epidermidis, Ti2Cu
National Category
Metallurgy and Metallic Materials
Identifiers
urn:nbn:se:uu:diva-378615 (URN)10.1016/j.msec.2018.12.050 (DOI)000457952800069 ()30678959 (PubMedID)
Available from: 2019-03-11 Created: 2019-03-11 Last updated: 2019-03-11Bibliographically approved
Sladkova, M., Cheng, J., Palmer, M., Chen, S., Lin, C., Xia, W., . . . de Peppo, G. M. (2019). Comparison of Decellularized Cow and Human Bone for Engineering Bone Grafts with Human Induced Pluripotent Stem Cells. Tissue Engineering. Part A, 25(3-4), 288-301
Open this publication in new window or tab >>Comparison of Decellularized Cow and Human Bone for Engineering Bone Grafts with Human Induced Pluripotent Stem Cells
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2019 (English)In: Tissue Engineering. Part A, ISSN 1937-3341, E-ISSN 1937-335X, Vol. 25, no 3-4, p. 288-301Article in journal (Refereed) Published
Abstract [en]

Bone engineering makes it possible to grow unlimited amounts of viable tissue products for basic and applied research, and for clinical applications. A common trend in tissue engineering is the use of decellularized tissue matrices as scaffolding materials, which display structural, mechanical, and biological attributes typical of the native tissue. Due to the limited availability and high cost of human samples, decellularized tissue matrices are typically derived from animal sources. It is unclear, however, whether interspecies differences in tissue parameters will influence the quality of tissue grafts that are engineered using human stem cells. In this study, decellularized cow and human bone scaffolds were compared for engineering bone grafts using human induced pluripotent stem cell-derived mesodermal progenitor cells. After seeding, the cell-scaffold constructs were cultured for 5 weeks in osteogenic medium under dynamic conditions in perfusion bioreactors. The architectural and chemical properties of the scaffolds were studied using microscopic, spectroscopic, and thermogravimetric techniques, while cell behavior and formation of mineralized tissue were assessed using a combination of molecular assays, histological methods, and imaging technologies. The results show that while scaffolds derived from cow and human bone differ somewhat in architecture and composition, both equally support cell viability, tissue growth, and formation of a mineralized bone matrix. Taken together, the results suggest that scaffolds derived from cow bone represent a suitable and convenient alternative to engineer human bone grafts for various biomedical applications.

Place, publisher, year, edition, pages
MARY ANN LIEBERT, INC, 2019
Keywords
biomaterial scaffold, bone engineering, induced pluripotent stem cells, mesenchymal stem cells, osteogenic differentiation, tissue decellularization
National Category
Biomaterials Science Engineering and Technology
Identifiers
urn:nbn:se:uu:diva-369891 (URN)10.1089/ten.tea.2018.0149 (DOI)000448565100001 ()
Funder
EU, FP7, Seventh Framework Programme
Note

De 2 första författarna delar förstaförfattarskapet.

Available from: 2018-12-19 Created: 2018-12-19 Last updated: 2019-04-17Bibliographically approved
Tkachenko, S., Datskevich, O., Kulak, L., Persson, C. & Engqvist, H. (2019). The Effect of Al Addition on the Tribological Behavior of Ti-Si-Zr Alloys. Journal of tribology, 141(4), Article ID 041604.
Open this publication in new window or tab >>The Effect of Al Addition on the Tribological Behavior of Ti-Si-Zr Alloys
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2019 (English)In: Journal of tribology, ISSN 0742-4787, E-ISSN 1528-8897, Vol. 141, no 4, article id 041604Article in journal (Refereed) Published
Abstract [en]

While commercial biomedical titanium alloys present excellent biocompatibility and corrosion resistance, their poor wear resistance remains a major limitation. In this study, alloying with aluminum was used to improve the tribological performance of an experimental Ti-Si-Zr alloy. The effect of Al content on the alloy's microstructure and mechanical properties was evaluated using X-ray diffraction (XRD), scanning electron microscopy (SEM), and Vickers hardness measurements. Sliding wear testing was performed in a ball-on-disk setup, using stainless steel and silicon nitride counterparts and serum solution lubrication. Microstructural examinations showed that an increase in Al content induced a change from eutectic cell microstructure to regular near-equiaxed particles and produced a solid solution strengthening, increasing alloy's hardness. The adhesive tendencies of the alpha-Ti matrix to the counterpart dominated the frictional response, and a lower friction coefficient was found against silicon nitride compared to stainless steel. In wear tests against stainless steel counterparts, the alloys showed significantly higher wear rates than the CoCr and Ti-6Al-4V references due to severe abrasive wear, induced by the adhesion of titanium matrix to the counterpart. The Al addition had a positive effect on the wear resistance against silicon nitride due to the solid solution strengthening and the change in microstructure, which reduced the risk of brittle delamination. However, while this gave a trend for a lower wear rate against silicon nitride than the Ti-6Al-4V alloy, the wear rate was still approximately three times higher than that of CoCr.

Keywords
nonferrous metals, sliding wear, electron microscopy, hardness, two-body abrasion
National Category
Tribology (Interacting Surfaces including Friction, Lubrication and Wear) Metallurgy and Metallic Materials
Identifiers
urn:nbn:se:uu:diva-379021 (URN)10.1115/1.4042098 (DOI)000459212000009 ()
Available from: 2019-03-12 Created: 2019-03-12 Last updated: 2019-03-12Bibliographically approved
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
Open this publication in new window or tab >>Titanium surface modification to enhance antibacterial and bioactive properties while retaining biocompatibility
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2019 (English)In: Materials science & engineering. C, biomimetic materials, sensors and systems, ISSN 0928-4931, E-ISSN 1873-0191, Vol. 96, p. 272-279Article in journal (Refereed) 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.

Keywords
Titanium, Antibacterial, Bioactivity, Cell viability, Sodium titanate, Calcium titanate
National Category
Materials Engineering
Identifiers
urn:nbn:se:uu:diva-358023 (URN)10.1016/j.msec.2018.11.021 (DOI)000456760700027 ()30606532 (PubMedID)
Funder
Vinnova
Available from: 2018-08-23 Created: 2018-08-23 Last updated: 2019-03-15Bibliographically approved
Filho, L., Schmidt, S., Leifer, K., Engqvist, H., Högberg, H. & Persson, C. (2019). Towards Functional Silicon Nitride Coatings for Joint Replacements. Coatings, 9(2), Article ID 73.
Open this publication in new window or tab >>Towards Functional Silicon Nitride Coatings for Joint Replacements
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2019 (English)In: Coatings, ISSN 2079-6412, Vol. 9, no 2, article id 73Article in journal (Refereed) Published
Abstract [en]

Silicon nitride (SiNx) coatings are currently under investigation as bearing surfaces for joint implants, due to their low wear rate and the good biocompatibility of both coatings and their potential wear debris. The aim of this study was to move further towards functional SiNx coatings by evaluating coatings deposited onto CoCrMo surfaces with a CrN interlayer, using different bias voltages and substrate rotations. Reactive direct current magnetron sputtering was used to coat CoCrMo discs with a CrN interlayer, followed by a SiNx top layer, which was deposited by reactive high-power impulse magnetron sputtering. The interlayer was deposited using negative bias voltages ranging between 100 and 900 V, and 1-fold or 3-fold substrate rotation. Scanning electron microscopy showed a dependence of coating morphology on substrate rotation. The N/Si ratio ranged from 1.10 to 1.25, as evaluated by X-ray photoelectron spectroscopy. Vertical scanning interferometry revealed that the coated, unpolished samples had a low average surface roughness between 16 and 33 nm. Rockwell indentations showed improved coating adhesion when a low bias voltage of 100 V was used to deposit the CrN interlayer. Wear tests performed in a reciprocating manner against Si3N4 balls showed specific wear rates lower than, or similar to that of CoCrMo. The study suggests that low negative bias voltages may contribute to a better performance of SiNx coatings in terms of adhesion. The low wear rates found in the current study support further development of silicon nitride-based coatings towards clinical application.

Keywords
silicon nitride, coating, reactive high-power impulse magnetron sputtering, wear, joint replacements
National Category
Manufacturing, Surface and Joining Technology
Identifiers
urn:nbn:se:uu:diva-379945 (URN)10.3390/coatings9020073 (DOI)000460700700011 ()
Available from: 2019-03-25 Created: 2019-03-25 Last updated: 2019-03-25Bibliographically approved
Procter, P., Pujari-Palmer, M., Hulsart Billström, G., Insley, G., Larsson, S. & Engqvist, H. (2018). A new ex-vivo murine model for evaluation of adhesiveness of a novel biomimetic bone glue. In: : . Paper presented at 34th Annual Meeting of Orthopaedic Trauma association, October 17 – 20, 2018, Kissimmee (Orlando), FL, USA.
Open this publication in new window or tab >>A new ex-vivo murine model for evaluation of adhesiveness of a novel biomimetic bone glue
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2018 (English)Conference paper, Oral presentation with published abstract (Refereed)
Keywords
Tissue adhesive, biomaterial, calcium phosphate
National Category
Medical Materials
Research subject
Engineering Science with specialization in Materials Science
Identifiers
urn:nbn:se:uu:diva-366372 (URN)
Conference
34th Annual Meeting of Orthopaedic Trauma association, October 17 – 20, 2018, Kissimmee (Orlando), FL, USA
Funder
Swedish Foundation for Strategic Research , RMA15-0110
Available from: 2018-11-20 Created: 2018-11-20 Last updated: 2019-03-06Bibliographically approved
Pujari-Palmer, M., Guo, H., Wenner, D., Autefage, H., Spicer, C. D., Stevens, M. M., . . . Engqvist, H. (2018). A Novel Class of Injectable Bioceramics that Glue Tissues and Biomaterials. Materials, 11(12), Article ID 2492.
Open this publication in new window or tab >>A Novel Class of Injectable Bioceramics that Glue Tissues and Biomaterials
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2018 (English)In: Materials, ISSN 1996-1944, E-ISSN 1996-1944, Vol. 11, no 12, article id 2492Article in journal (Refereed) Published
Abstract [en]

Calcium phosphate cements (CPCs) are clinically effective void fillers that are capable of bridging calcified tissue defects and facilitating regeneration. However, CPCs are completely synthetic/inorganic, unlike the calcium phosphate that is found in calcified tissues, and they lack an architectural organization, controlled assembly mechanisms, and have moderate biomechanical strength, which limits their clinical effectiveness. Herein, we describe a new class of bioinspired CPCs that can glue tissues together and bond tissues to metallic and polymeric biomaterials. Surprisingly, alpha tricalcium phosphate cements that are modified with simple phosphorylated amino acid monomers of phosphoserine (PM-CPCs) bond tissues up to 40-fold stronger (2.5–4 MPa) than commercial cyanoacrylates (0.1 MPa), and 100-fold stronger than surgical fibrin glue (0.04 MPa), when cured in wet-field conditions. In addition to adhesion, phosphoserine creates other novel properties in bioceramics, including a nanoscale organic/inorganic composite microstructure, and templating of nanoscale amorphous calcium phosphate nucleation. PM-CPCs are made of the biocompatible precursors calcium, phosphate, and amino acid, and these represent the first amorphous nano-ceramic composites that are stable in liquids.

Keywords
cement, tissue adhesive, phosphoserine, self-assembly, amorphous calcium phosphate (ACP), correlation nuclear magnetic resonance (NMR) spectroscopy, bioinspired, biomaterial
National Category
Composite Science and Engineering Ceramics Medical Materials Biomaterials Science
Research subject
Engineering Science with specialization in Materials Science
Identifiers
urn:nbn:se:uu:diva-369970 (URN)10.3390/ma11122492 (DOI)000456419200150 ()30544596 (PubMedID)
Funder
Swedish Foundation for Strategic Research , RMA15-0110
Available from: 2018-12-18 Created: 2018-12-18 Last updated: 2019-02-18Bibliographically approved
Qin, T., Qin, W., Ma, M., Zhang, D., Hu, S., Zhang, P., . . . Engqvist, H. (2018). A novel rapid synthesis, characterization and applications of calcium phosphate nanospheres from Baltic seawater. Ceramics International, 44(8), 9076-9079
Open this publication in new window or tab >>A novel rapid synthesis, characterization and applications of calcium phosphate nanospheres from Baltic seawater
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2018 (English)In: Ceramics International, ISSN 0272-8842, E-ISSN 1873-3956, Vol. 44, no 8, p. 9076-9079Article in journal (Refereed) Published
Abstract [en]

Due to the considerable high bio-compatibility, calcium phosphate nanoparticles are widely used in biomedical applications. This study proposes a novel strategy for low-cost manufacturing calcium phosphate nanoporous spheres. The controlled reaction only took less than five minutes, when using Baltic seawater with the dissolved calcium concentration of 2.2 mM as the calcium resources. Porous nanospheres were obtained, with spheres ranging from 50 to 130 nm. The obtained nanospheres possess high drug-loading capacity and exhibit sustained release and pH-dependent properties. In addition, this method provides a general efficient strategy to synthesize other low-cost inorganic nanospheres from seawater.

Place, publisher, year, edition, pages
ELSEVIER SCI LTD, 2018
Keywords
Seawater, Nanosphere, Low cost, Drug, Calcium phosphate
National Category
Materials Chemistry Engineering and Technology
Identifiers
urn:nbn:se:uu:diva-356619 (URN)10.1016/j.ceramint.2018.02.114 (DOI)000430522200044 ()
Available from: 2018-08-20 Created: 2018-08-20 Last updated: 2018-08-23Bibliographically approved
Luo, J., Engqvist, H. & Persson, C. (2018). A ready-to-use acidic, brushite-forming calcium phosphate cement. Acta Biomaterialia, 81, 304-314
Open this publication in new window or tab >>A ready-to-use acidic, brushite-forming calcium phosphate cement
2018 (English)In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 81, p. 304-314Article in journal (Refereed) Published
Abstract [en]

Premixed calcium phosphate cements have been developed to simplify the usage of traditional calcium phosphate cements and reduce the influence of the setting reaction on the delivery process. However, difficulties in achieving a good cohesion, adequate shelf life and sufficient mechanical properties have so far impeded their use in clinical applications, especially for the more degradable acidic calcium phosphate cements. In this study, a brushite cement was developed from a series of ready-to-use calcium phosphate pastes. The brushite cement paste was formed via mixing of a monocalcium phosphate monohydrate (MCPM) paste and a beta-tricalcium phosphate (beta-TCP) paste with good injectability and adequate shelf life. The MCPM paste was based on a water-immiscible liquid with two surfactants and the beta-Tcp paste on a sodium hyaluronate aqueous solution. The effect of citric acid as a retardant was assessed. Formulations with suitable amounts of citric acid showed good cohesion and mechanical performance with potential for future clinical applications. Statement of Significance Acidic calcium phosphate cements have attracted extensive attention as bone substitute materials due to their ability to resorb faster than basic calcium phosphate cements in vivo. However, traditionally, short working times and low mechanical strength have limited their clinical application. Premixed cements could simplify the clinical use as well as improve property reproducibility, but short shelf lives, low cohesion and low mechanical properties have restricted the development. In this study, an injectable ready-to-use two-phase system consisting of an MCPM paste and a beta-TCP paste was developed based on acidic cement. It shows good cohesion, compressive strength and adequate shelf life, which has the potential to be used in a dual chamber system for simplified and fast filling of bone defects in a minimally invasive manner. This will reduce surgery time, decrease the risk of contamination and ensure repeatable results.

Keywords
Ready-to-use, Acidic calcium phosphate cement, Brushite, Cohesion, Injectability, Shelf life
National Category
Ceramics
Identifiers
urn:nbn:se:uu:diva-372719 (URN)10.1016/j.actbio.2018.10.001 (DOI)000451937500024 ()30291976 (PubMedID)
Funder
Swedish Foundation for Strategic Research
Available from: 2019-01-08 Created: 2019-01-08 Last updated: 2019-01-08Bibliographically approved
Xia, W., Cai, B., Engqvist, H. & Bredenberg, S. (2018). A transdermal drug administration device. JP2018513121A.
Open this publication in new window or tab >>A transdermal drug administration device
2018 (English)Patent (Other (popular science, discussion, etc.))
National Category
Engineering and Technology
Identifiers
urn:nbn:se:uu:diva-372236 (URN)
Patent
JP2018513121A
Available from: 2019-01-07 Created: 2019-01-07 Last updated: 2019-01-07
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0001-9529-650X

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