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  • 1.
    Brohede, Ulrika
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Atluri, Rambabu
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Garcia Bennett, Alfonso
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Strömme, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Sustained Release from Mesosporous Nanoparticles: evaluation of structural properties associated with controlled release rate2008In: Current Drug Delivery, ISSN 1567-2018, E-ISSN 1875-5704, Vol. 5, no 3, p. 177-185Article in journal (Refereed)
    Abstract [en]

    We present here a detailed study of the controlled release of amino acid derived amphiphilic molecules from the internal pore structure of mesoporous nanoparticle drug delivery systems with different structural properties; namely cubic and hexagonal structures of various degrees of complexity. The internal pore surface of the nanomaterials presented has been functionalised with amine moieties through a one pot method. Release profiles obtained by Alternating Ionic Current measurements are interpreted in terms of specific structural and textural parameters of the porous nanoparticles such as pore geometry and connectivity. Results indicate that diffusion coefficients are lower by as much as four orders of magnitude in 2-dimensional structures in comparison to 3-dimensional mesoporous solids. A fast release in turn is observed from mesocaged materials AMS-9 and AMS-8 where the presence of structural defects is thought to lead to a slightly lower diffusion coefficient in the latter. Amount of pore wall functionalisation and number of binding sites on the model drug are found to have little effect on the drug release rate.

  • 2.
    Brohede, Ulrika
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Forsgren, Johan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Roos, Stefan
    Mihranyan, Albert
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Engqvist, Håkan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Strömme, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Multifunctional implant coatings providing possibilities for fast antibiotics loading with subsequent slow release2009In: Journal of materials science. Materials in medicine, ISSN 0957-4530, E-ISSN 1573-4838, Vol. 20, no 9, p. 1859-1867Article in journal (Refereed)
    Abstract [en]

    The possibility to fast-load biomimetic hydroxyapatite coatings on surgical implant with the antibiotics Amoxicillin, Gentamicin sulfate, Tobramycin and Cephalothin has been investigated in order to develop a multifunctional implant device offering sustained local anti-bacterial treatment and giving the surgeon the possibility to choose which antibiotics to incorporate in the implant at the site of surgery. Physical vapor deposition was used to coat titanium surfaces with an adhesion enhancing gradient layer of titanium oxide having an amorphous oxygen poor composition at the interface and a crystalline bioactive anatase TiO2 composition at the surface. Hydroxyapatite (HA) was biomimetically grown on the bioactive TiO2 to serve as a combined bone in-growth promoter and drug delivery vehicle. The coating was characterized using scanning and transmission electron microscopy, X-ray diffraction and X-ray photoelectron spectroscopy. The antibiotics were loaded into the HA coatings via soaking and the subsequent release and antibacterial effect were analyzed using UV spectroscopy and examination of inhibition zones in a Staphylococcus aureus containing agar. It was found that a short drug loading time of 15 min ensured antibacterial effects after 24 h for all antibiotics under study. It was further found that the release processes of Cephalothin and Amoxicillin consisted of an initial rapid drug release that varied unpredictably in amount followed by a reproducible and sustained release process with a release rate independent of the drug loading times under study. Thus, implants that have been fast-loaded with drugs could be stored for ~10 min in a simulated body fluid after loading to ensure reproducibility in the subsequent release process. Calculated release rates and measurements of drug amounts remaining in the samples after 22 h of release indicated that a therapeutically relevant dose could be achieved close to the implant surface for about 2 days. Concluding, the present study provides an outline for the development of a fast-loading slow-release surgical implant kit where the implant and the drug are separated when delivered to the surgeon, thus constituting a flexible solution for the surgeon by offering the choice of quick addition of antibiotics to the implant coating based on the patient need.

  • 3.
    Brohede, Ulrika
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Technology, Department of Engineering Sciences. Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Nilsson, Martin
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Technology, Department of Engineering Sciences. Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Strömme, Maria
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Technology, Department of Engineering Sciences. Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    The importance of water-cellulose interactions for the drug release process2004In: The Swedish Academy of Pharmaceutical Sciences conference “Styrning av läkemedelstillförsel aktuell svensk forskning” 2-3 June, Göteborg, contribution P9 (2004), 2004Conference paper (Refereed)
  • 4.
    Brohede, Ulrika
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials. Nanoteknologi.
    Strömme, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials. Nanoteknologi.
    Percolating ion transport in binary mixtures with high dielectric loss: Dry dielectric spectroscopy recordings and wet time-dependent salt release measurements.2006Conference paper (Other academic)
  • 5.
    Brohede, Ulrika
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Strømme, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Percolation phenomena in controlled drug release matrices studied by dielectric spectroscopy and the alternating ionic current method2007In: Journal of Non-Crystalline Solids, ISSN 0022-3093, E-ISSN 1873-4812, Vol. 353, no 47-51, p. 4506-4514Article in journal (Refereed)
    Abstract [en]

    The combined radial and axial ionic drug release from – as well as the percolating ionic conductivity in – cylindrical tablets was investigated by the alternating ionic current (AIC) method and dielectric spectroscopy (DS), respectively. The binary tablets consisted of mixtures of insulating ethyl cellulose and the poor ionic conductor model drug NaCl at nine different concentrations. We found that the dc conductivity, extracted from DS in a well-defined range of frequencies by a power-law method, could be described by a NaCl volume fraction percolation threshold of 0.06 in a 3D conducting network. The low threshold was explained by water-layer-assisted ion conduction in μm-sized ethyl cellulose channels between NaCl grains as probed by Hg porosimetry and SEM. The drug release process, as probed by AIC, could be described by a matrix porosity percolation threshold of 0.22, equivalent to a NaCl volume fraction of 0.13. The higher percolation threshold found in the drug release experiments as compared to the DS recordings could be explained by the different probing mechanisms of the analysis methods. The present study should provide valuable knowledge for the analysis of a broad class of ion conducting systems for which the frequency response of the dc ion conductivity is superimposed on other dielectric processes in the dielectric spectrum. It also brings forward knowledge important for the development of controlled drug-delivery vehicles as the presented findings show that the drug release from matrix tablets with unsealed tablet walls substantially differs from earlier investigated release processes for which the drug has only been allowed to escape through one of the flat tablet surfaces.

  • 6.
    Brohede, Ulrika
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Valizadeh, Sima
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Strømme, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Frenning, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Percolative drug diffusion from cylindrical matrix systems with unsealed boundaries2007In: Journal of Pharmaceutical Sciences, ISSN 0022-3549, E-ISSN 1520-6017, Vol. 96, no 11, p. 3087-3099Article in journal (Refereed)
    Abstract [en]

    Release of NaCl in both the axial and radial directions from cylindrical ethyl cellulose tablets were investigated by the alternating ionic current method. The pore structure of the investigated binary mixtures was examined by mercury porosimetry and scanning electron microscopy, and the nm range fractal surface dimension of tablet pore walls was extracted from krypton gas adsorption isotherms. The drug release was shown to consist of two overlapping processes of which the first was ascribed to dissolution of NaCl close to the tablet boundary followed by subsequent diffusion through a thin ethyl cellulose layer and a second from which a porosity percolation threshold of 0.22 could be extracted. As well, a cross-over to effective-medium behaviour at a porosity of 0.44 was observed. The presented findings showed that drug release from matrix tablets with unsealed tablet walls substantially differs from earlier investigated release processes for which the drug has only been allowed to escape through one of the flat tablet surfaces. Thus, the present study brings forward knowledge important for the tailoring of controlled drug delivery vehicles with optimum release patterns.

  • 7.
    Brohede, Ulrika
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Zhao, Shuxi
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Solid State Physics.
    Lindberg, Fredrik
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Mihranyan, Albert
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Forsgren, Johan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Strömme, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Engqvist, Håkan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    A novel graded bioactive high adhesion implant coating2009In: Applied Surface Science, ISSN 0169-4332, E-ISSN 1873-5584, Vol. 255, no 17, p. 7723-7728Article in journal (Refereed)
    Abstract [en]

     One method to increase the clinical success rate of metal implants is to increase their bone bonding properties, i.e. to develop a bone   bioactive surface leading to reduced risks of interfacial problems.   Much research has been devoted to modifying the surface of metals to   make them become bioactive. Many of the proposed methods include   depositing a coating on the implant. However, there is a risk of coating failure due to low substrate adhesion. This paper describes a method to obtain bioactivity combined with a high coating adhesion via   a gradient structure of the coating. Gradient coatings were deposited   on Ti (grade 5) using reactive magnetron sputtering with increasing   oxygen content. To increase the grain size in the coating, all coatings   were post annealed at 385 degrees C. The obtained coating exhibited a gradual transition over 70 nm from crystalline titanium oxide (anatase)  at the surface to metallic Ti in the substrate, as shown using  cross-section transmission electron microscopy and X-ray photoelectron   spectroscopy depth pro. ling. Using scratch testing, it could be shown that the adhesion to the substrate was well above 1 GPa. The bioactivity of the coating was verified in vitro by the spontaneous   formation of hydroxylapatite upon storage in phosphate buffer solution at 37 degrees C for one week.   The described process can be applied to implants irrespective of bulk  metal in the base and should introduce the possibility to create safer permanent implants like reconstructive devices, dental, or spinal implants.

  • 8.
    Brohede, Ulrika
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Zhao, Suxi
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Lindberg, Fredrik
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Mihranyan, Albert
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Engqvist, Håkan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Strömme, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Bioactive coatings on metal implants combined with drug delivery features2008Conference paper (Refereed)
  • 9.
    Engqvist, Håkan
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Brohede, Ulrika
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials. Nanoteknologi och Funktionella Material.
    Mihranyan, Albert
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials. Nanoteknologi och Funktionella material.
    Zhao, Shuxi
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials. Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Strömme, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials. Nanoteknologi och Funktionella material.
    Bioactive Coatings Combined with Drug Delivery Features2007Conference paper (Refereed)
  • 10.
    Forsgren, Johan
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Brohede, Ulrika
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Mihranyan, Albert
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Engqvist, Håkan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Strömme, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Fast loading, slow release: a new strategy for incorporating antibiotics2009In: Key Engineering Materials, ISSN 1662-9795, Vol. 396-398, p. 523-526Article in journal (Refereed)
  • 11.
    Forsgren, Johan
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Brohede, Ulrika
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Mihranyan, Albert
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Engqvist, Håkan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Strömme, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Fast loading, slow release a new strategy for incorporating antibiotics to hydroxyapatite2008In: Bioceramics 21, 2008Conference paper (Refereed)
  • 12.
    Forsgren, Johan
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials. Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Brohede, Ulrika
    Sandvik AB, Stockholm.
    Piskounova, Sonya
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Materials Chemistry, Polymer Chemistry.
    Mihranyan, Albert
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Maria, Strømme
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Engqvist, Håkan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    In Vivo Evaluation of Functionalized Biomimetic Hydroxyapatite for Local Delivery of Active Agents2011In: Journal of Biomaterials and Nanobiotechnology, ISSN 2158-7027, 2158-7043, Vol. 2, no 2, p. 149-154Article in journal (Refereed)
    Abstract [en]

    This study was carried out to investigate the biological response in vivo to biomimetic hydroxyapatite implant coatings functionalized with bisphosphonates and bone morphogenetic proteins. The functionalization was carried out by a simple soaking procedure in the operating room immediately prior to surgery. Cylindrical titanium samples with and without coatings were implanted in the distal femoral epiphysis of sheep and retrieved after 6 weeks. The histological analysis proved that all samples were integrated well in the tissue with no signs of intolerance. Fewer osteoclasts were observed in the vicinity of bisphosphonate-functionalized samples and the bone was denser around these samples compared to the other samples. Samples functionalized with bone morphogenetic protein induced more bone/implant contact but showed a more inconsistent outcome with reduced bone density around the samples. This study demonstrates a simple method to functionalize implant coatings, which provides surgeons with an option of patient-specific functionalization of implants. The observed biological impact due to the delivery of active molecules from the coatings suggests that this strategy may also be employed to deliver antibiotics from similar coatings.

  • 13.
    Forsgren, Johan
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials. Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Brohede, Ulrika
    Sandvik AB, Stockholm.
    Strømme, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Engqvist, Håkan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Co-loading of bisphosphonates and antibiotics to a biomimetic hydroxyapatite coating2011In: Biotechnology letters, ISSN 0141-5492, E-ISSN 1573-6776, Vol. 33, no 6, p. 1265-1268Article in journal (Refereed)
    Abstract [en]

    We have incorporated bisphosphonates and antibiotics simultaneously into a biomimetic hydroxyapatite implant coating aiming to use the interaction between drug-molecules and hydroxyapatite to enable local release of the two different substances to obtain a dual biological effect. A sustained release over for 43 h of antibiotics (cephalothin) was achieved without negative interference from the presence of the bisphosphonate (clodronate) which, in turn, successfully bonded to the coating surface. To our knowledge, this is the first study that indicates the possibility to simultaneously incorporate both antibiotics and bisphosphonates to an implant coating, a strategy that is believed to improve implant stability and reduce implant-related infections.

  • 14.
    Garcia-Bennett, Alfonso E.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Brohede, Ulrika
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Hodgkins, Robert
    Hedin, Niklas
    Strømme, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    A mechanistic study of the formation of mesoporous structures from in situ AC conductivity measurements2007In: Langmuir, ISSN 0743-7463, E-ISSN 1520-5827, Vol. 23, no 19, p. 9875-9881Article in journal (Refereed)
    Abstract [en]

    The purpose of this work is to study the kinetics of self-assembly in the formation mechanism of anionic templated mesoporous solids (AMS-n) during die first few seconds of the synthesis as well as to demonstrate the use of alternating ion current (AIC) conductivity measurements to follow the self-assembly in complex hybrid systems. The formation of different AMS-n caged-type mesostructures through the delayed addition of the silica source is demonstrated and explained in terms of the interaction between the co-structure-directing agent (CSDA) and the oppositely charged surfactant headgroup regions. Our findings, supported by transmission electron microscopy, 29Si magic angle spinning nuclear magnetic resonance (MAS NMR) spectroscopy, dynamic light scattering (DLS) measurements, and powder X-ray diffraction suggest that the interaction of the CSDA with the surfactant headgroup occurs within seconds after its addition to the synthesis gel leading to interaction between the polymerizing CSDAs and the oppositely charged micelle and to an increase in the micelle-CSDA aggregate size. Both DLS and AIC measurements agree that this process occurs within the first 1000 s after addition of the CSDA to the synthesis gel at room temperature. In addition to the mechanistic study it was found that the intermediate materials are comprised of a three-layer entity. Time-dependent 29Si MAS NMR studies reveal that an organo-silica layer forms around the micelles prior to a condensed outer inorganic shell of silica.

  • 15.
    Lilja, Mirjam
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Sörensen, Jan
    Brohede, Ulrica
    Åstrand, Maria
    Procter, Philip
    Arnoldi, Jörg
    Steckel, Hartwig
    Strömme, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Drug eluting hydroxyapatite coatings for biomedical applications2013In: European Cells and Materials, ISSN 1473-2262, E-ISSN 1473-2262, ISSN 1473-2262, Vol. 26, no 2, p. 36-Article in journal (Refereed)
  • 16.
    Lilja, Mirjam
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Sörensen, Jan
    Brohede, Ulrica
    Åstrand, Maria
    Procter, Philip
    Arnoldi, Jörg
    Steckel, Hartwig
    Strömme, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Drugeluting hydroxyapatite coatings for biomedical applications2013In: Scandinavian Society for Biomaterials, 2013Conference paper (Refereed)
  • 17.
    Lilja, Mirjam
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Sörensen, Jan Henrik
    Christian-Albrechts Universitet Kiel.
    Brohede, Ulrika
    Sandvik Coromant.
    Åstrand, Maria
    Sandvik Coromant.
    Procter, Philip
    Arnoldi, Jörg
    Steckel, Hartwig
    Christian-Albrechts Universitet Kiel.
    Strømme, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Drug loading and release of Tobramycin from Hydroxyapatite coated fixation pins2013In: Journal of materials science. Materials in medicine, ISSN 0957-4530, E-ISSN 1573-4838, Vol. 24, no 9, p. 2265-2274Article in journal (Refereed)
    Abstract [en]

    This paper evaluates the loading and release properties of Tobramycin incorporated by adsorptive loading from a solution into plasma sprayed and biomimetically coated Hydroxyapatite (HA) fixation pins. The aim of this study is to contribute towards designing a functional implant surface offering local release of the antibiotic agent to prevent post-surgical infections. Cathodic arc deposition is used to coat stainless steel fixation pins with a bioactive, anatase phase dominated, TiO2 coating onto which a HA layer is grown biomimetically. The loading and release properties are evaluated by studying the subsequent release of Tobramycin using high performance liquid chromatography and correlated to the differences in HA coating microstructure and the physical conditions under loading. The results from these studies show that a dual loading strategy consisting of a solution temperature of 90 °C and a pressure of 6 bar during a loading time of 5 min release a sufficient amount of Tobramycin to guarantee the inhibition of Staphylococcus aureus up to 2 days for plasma sprayed HA coatings and for 8 days for biomimetic coatings. The present study emphasizes the advantages of the nanoporous structure of biomimetically deposited HA over the more dense structure of plasma sprayed HA coatings in terms of antibiotic incorporation and subsequent sustained release and provides a valuable outline for the design of implant surfaces aiming for a fast-loading and controlled, local drug administration.

  • 18. Piskounova, S.
    et al.
    Forsgren, Johan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Brohede, Ulrika
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Engqvist, Håkan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Strömme, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Immobilization of bone morphogenetic protein 2 on bioactive titanium/hydroxyapatite surfaces for multifaceted osteogenetic effect2009Conference paper (Refereed)
  • 19. Piskounova, S.
    et al.
    Forsgren, Johan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Brohede, Ulrika
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Engqvist, Håkan
    Strömme, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Mesenchymal stem cell behavior on bioactive crystalline titanium dioxide/hydroxyapatite surfaces functionalized with bone morphogenetic protein 22009Conference paper (Refereed)
  • 20.
    Piskounova, Sonya
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Materials Chemistry, Polymer Chemistry.
    Forsgren, Johan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Brohede, Ulrika
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Engqvist, Håkan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Strømme, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    In vitro characterization of bioactive titanium dioxide/hydroxyapatite surfaces functionalized with BMP-22009In: Journal of biomedical materials research. Part B, Applied biomaterials, ISSN 1552-4981, Vol. 91B, no 2, p. 780-787Article in journal (Refereed)
    Abstract [en]

    Poor implant fixation and bone resorption are two of the major challenges in modern orthopedics and are caused by poor bone/implant integration. In this work, bioactive crystalline titanium dioxide (TiO(2))/hydroxyapatite (HA) surfaces, functionalized with bone morphogenetic protein 2 (BMP-2), were evaluated as potential implant coatings for improved osseointegration. The outer layer consisted of HA, which is known to be osteoconductive, and may promote improved initial bone attachment when functionalized with active molecules such as BMP-2 in a soaking process. The inner layer of crystalline TiO(2) is bioactive and ensures long-term fixation of the implant, once the hydroxyapatite has been resorbed. The in vitro response of mesenchymal stem cells on bioactive crystalline TiO(2)/HA surfaces functionalized with BMP-2 was examined and compared with the cell behavior on nonfunctionalized HA layers, crystalline TiO(2) surfaces, and native titanium oxide surfaces. The crystalline TiO(2) and the HA surfaces showed to be more favorable than the native titanium oxide surface in terms of cell viability and cell morphology as well as initial cell differentiation. Furthermore, cell differentiation on BMP-2-functionalized HA surfaces was found to be significantly higher than on the other surfaces indicating that the simple soaking process can be used for incorporating active molecules, promoting fast bone osseointegration to HA layers.

  • 21. Stenlund, Patrik
    et al.
    Omar, Omar
    Brohede, Ulrika
    Norgren, Susanne
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Norlindh, Birgitta
    Johansson, Anna
    Lausmaa, Jukka
    Thomsen, Peter
    Palmquist, Anders
    Bone response to a novel Ti–Ta–Nb–Zr alloy2015In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 20, p. 165-175Article in journal (Refereed)
  • 22. Stenlund, Patrik
    et al.
    Omar, Omar
    Brohede, Ulrika
    Norgren, Susanne
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Norlindh, Birgitta
    Johansson, Anna
    Lausmaa, Jukka
    Thomsen, Peter
    Palmquist, Anders
    Bone response to a novel Ti-Ta-Nb-Zr alloy2015In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 20, p. 165-175Article in journal (Refereed)
    Abstract [en]

    Commercially pure titanium (cp-Ti) is regarded as the state-of-the-art material for bone-anchored dental devices, whereas the mechanically stronger alloy (Ti-6Al-4V), made of titanium, aluminum (Al) and vanadium (V), is regarded as the material of choice for high-load applications. There is a call for the development of new alloys, not only to eliminate the potential toxic effect of Al and V but also to meet the challenges imposed on dental and maxillofacial reconstructive devices, for example. The present work evaluates a novel, dual-stage, acid-etched, Ti-Ta-Nb-Zr alloy implant, consisting of elements that create low toxicity, with the potential to promote osseointegration in vivo. The alloy implants (denoted Ti-Ta-Nb-Zr) were evaluated after 7 days and 28 days in a rat tibia model, with reference to commercially pure titanium grade 4 (denoted Ti). Analyses were performed with respect to removal torque, histomorphometry and gene expression. The Ti-Ta-Nb-Zr showed a significant increase in implant stability over time in contrast to the Ti. Further, the histological and gene expression analyses suggested faster healing around the Ti-Ta-Nb-Zr, as judged by the enhanced remodeling, and mineralization, of the early-formed woven bone and the multiple positive correlations between genes denoting inflammation, bone formation and remodeling. Based on the present experiments, it is concluded that the Ti-Ta-Nb-Zr alloy becomes osseointegrated to at least a similar degree to that of pure titanium implants. This alloy is therefore emerging as a novel implant material for clinical evaluation.

  • 23.
    Strømme, Maria
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Atluri, Rambabu
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Brohede, Ulrika
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Frenning, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Garcia-Bennett, Alfonso. E
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Proton Absorption in As-Synthesized Mesoporous Silica Nanoparticles as a Structure-Function Relationship Probing Mechanism2009In: Langmuir, ISSN 0743-7463, E-ISSN 1520-5827, Vol. 25, no 8, p. 4306-4310Article in journal (Refereed)
    Abstract [en]

    A new method to investigate the effect of pore geometry on diffusion processes in mesoporous silica nanoparticles and other types of micro- and mesoporous structures is put forward. The method is based onthe study of proton diffusion from a liquid surrounding the mesoporous particles into the particle pore system. The proton diffusion properties are assessed for a variety of as-synthesized mesoporous nano- and microparticles with two-dimensional and three-dimensional connectivity. Results show that the diffusion coefficients are higher for the proton absorption process than for the release of surfactant template molecules, and that they overall follow the same trend with the more complex three-dimensional mesocaged particles showing the highest diffusion coefficients. The pore geometry (cylindrical pores versus cage-type pores) and structure connectivity are found to play a key role for the effects observed. The results put forward in the present work should offer a valuable tool in the development of porous nanomaterials in a range of applications including the use as catalysis and separation enhancers in the petrochemical industry, as scaffolds for hydrogen storage, and as drug delivery vehicles for sustained release and gene transfection.

  • 24.
    Strømme, Maria
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Brohede, Ulrika
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Atluri, Rambabu
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Garcia Bennett, Alfonso
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Mesoporous silica-based nanomaterials for drug delivery: evaluation of structural properties associated with release rate2009In: Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology, ISSN 1939-5116, Vol. 1, no 1, p. 140-148Article in journal (Refereed)
    Abstract [en]

    We present here a study of the controlled release of amino acid-derived amphiphilic molecules from the internal pore structure of mesoporous nanoparticle drug delivery systems with different structural properties, namely cubic and hexagonal structures of various degrees of complexity. The internal pore surface of the nanomaterials presented has been functionalised with amine moieties through a one-pot method. Release profiles obtained by conductivity measurements are interpreted in terms of specific structural and textural parameters of the porous nanoparticles, such as pore geometry and connectivity. Results indicate that diffusion coefficients are lower by as much 4 orders of magnitude in two-dimensional structures in comparison to three-dimensional mesoporous solids. A fast release in turn is observed from mesocaged materials AMS-9 and AMS-8, where the presence of structural defects is thought to lead to a slightly lower diffusion coefficient in the latter. We conclude that the use of single or mixed phases of these porous systems can be utilized to provide sustained release over long time periods and expect their use in a variety of formulations.

  • 25.
    Åberg, Jonas
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Brohede, Ulrika
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Mihranyan, Albert
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Strömme, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Engqvist, Håkan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Targeted local delivery of bisphophonate from orthopedic implants2008Conference paper (Refereed)
  • 26.
    Åberg, Jonas
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Brohede, Ulrika
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Mihranyan, Albert
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Strömme, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Engqvist, Håkan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Targeted Local Delivery of Bisphosphonate From Orthopaedic Implants2009In: BIOCERAMICS 21 / [ed] Prado M, Zavaglia C, 2009, Vol. 396-398, p. 543-546Conference paper (Refereed)
  • 27.
    Åberg, Jonas
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Brohede, Ulrika
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Mihranyan, Albert
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Strømme, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Engqvist, Håkan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Bisphosphonate incorporation in surgical implant coatings by fast loading and co-precipitation at low drug concentrations2009In: Journal of materials science. Materials in medicine, ISSN 0957-4530, E-ISSN 1573-4838, Vol. 20, no 10, p. 2053-2061Article in journal (Refereed)
    Abstract [en]

    The objectives of the present work was to evaluate the possibility for fast loading by soaking of bisphosphonates (BPs) into hydroxylapatite (HA) implant coatings biomimetically grown on crystalline TiO(2) surfaces, and also investigate the influence of different BP loading concentrations in a buffer during co-precipitation of a calcium phosphate containing layer onto these surfaces. The co-precipitation method created coatings that contained BPs throughout most of the coating layer, but the presence of BPs in the buffer hindered the formation of a bulk HA-layer, thus resulting in very thin coatings most likely consisting of islands built up by a calcium phosphate containing BPs. The coatings biomimetically grown on TiO(2) surfaces, were shown to consist of crystalline HA. Soaking of these coatings during 15 min only in a low BPs concentration containing buffer yielded a concentration on the coating surface of the same order of magnitude as obtained with soaking during 60 min in significantly higher concentrated buffers. This could be of advantage during surgery since the operating surgeon could make a fast decision whether or not to include the drugs in the coating based on the need of the particular patient at hand. The BPs present on the surface of the fast-loaded HA coatings were found to be strongly bound, something which should be beneficial for in vivo use. Both the co-precipitation method and the fast loading by soaking method investigated here are promising techniques for loading of BPs onto surgical implants. The simplicity of both methods is an advantage since implants can have spatially complicated structures.

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