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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.
    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.

  • 2.
    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.

  • 3.
    Carlsson, Daniel O.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Hua, Kai
    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.
    Mihranyan, Albert
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Aspirin degradation in surface-charged TEMPO-oxidized mesoporous crystalline nanocellulose2013In: International Journal of Pharmaceutics, ISSN 0378-5173, E-ISSN 1873-3476, Vol. 461, no 1-2, p. 74-81Article in journal (Refereed)
    Abstract [en]

    TEMPO-mediated surface oxidation of mesoporous highly crystalline Cladophora cellulose was used to introduce negative surface charges onto cellulose nanofibrils without significantly altering other structural characteristics. This enabled the investigation of the influence of mesoporous nanocellulose surface charges on aspirin chemical stability to be conducted. The negative surface charges (carboxylate content 0.44 ± 0.01 mmol/g) introduced on the mesoporous crystalline nanocellulose significantly accelerated aspirin degradation, compared to the starting material which had significantly less surface charge (0.06 ± 0.01 mmol/g). This effect followed from an increased aspirin amorphisation ability in mesopores of the oxidized nanocellulose. These results highlight the importance of surface charges in formulating nanocellulose for drug delivery.

  • 4.
    Carlsson, Daniel O
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Hua, Kai
    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.
    Mihranyan, Albert
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Aspirin stability in anionically charged crystalline nanocellulose2013Conference paper (Refereed)
  • 5.
    Carlsson, Daniel O.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Hua, Kai
    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.
    Forsgren, Johan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Aspirin degradation in surface-charged TEMPO-oxidized mesoporous crystalline nanocellulose2014In: International Journal of Pharmaceutics, ISSN 0378-5173, E-ISSN 1873-3476, Vol. 461, p. 74-81Article in journal (Refereed)
  • 6.
    Forsgren, Johan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Assessment of Batch-to-Batch-Variability in Representative Nanoparticle Syntheses with Characterisation of OECD Proposed Parameters.2013Conference paper (Refereed)
  • 7.
    Forsgren, Johan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Batch-to-batch reproducibility: a challenge for safety assessment and regulation2013Conference paper (Refereed)
  • 8.
    Forsgren, Johan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Functional Ceramics in Biomedical Applications: On the Use of Ceramics for Controlled Drug Release and Targeted Cell Stimulation2010Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Ceramics are distinguished from metals and polymers by their inorganic nature and lack of metallic properties. They can be highly crystalline to amorphous, and their physical and chemical properties can vary widely. Ceramics can, for instance, be made to resemble the mineral phase in bone and are therefore an excellent substitute for damaged hard tissue. They can also be made porous, surface active, chemically inert, mechanically strong, optically transparent or biologically resorbable, and all these properties are of interest in the development of new materials intended for a wide variety of applications. In this thesis, the focus was on the development of different ceramics for use in the controlled release of drugs and ions. These concepts were developed to obtain improved therapeutic effects from orally administered opioid drugs, and to reduce the number of implant-related infections as well as to improve the stabilization of prosthetic implants in bone.

    Geopolymers were used to produce mechanically strong and chemically inert formulations intended for oral administration of opioids. The carriers were developed to allow controlled release of the drugs over several hours, in order to improve the therapeutic effect of the substances in patients with severe chronic pain. The requirement for a stable carrier is a key feature for these drugs, as the rapid release of the entire dose, due to mechanical or chemical damage to the carrier, could have lethal effects on the patient because of the narrow therapeutic window of opioids. It was found that it was possible to profoundly retard drug release and to achieve almost linear release profiles from mesoporous geopolymers when the aluminum/silicon ratio of the precursor particles and the curing temperature were tuned.

    Ceramic implant coatings were produced via a biomimetic mineralization process and used as carriers for various drugs or as an ion reservoir for local release at the site of the implant. The formation and characteristics of these coatings were examined before they were evaluated as potential drug carriers. It was demonstrated that these coatings were able to carry antibiotics, bisphosphonates and bone morphogenetic proteins to obtain a sustained local effect, as they were slowly released from the coatings.

     

    List of papers
    1. A ceramic drug delivery vehicle for oral administration of highly potent opioids
    Open this publication in new window or tab >>A ceramic drug delivery vehicle for oral administration of highly potent opioids
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    2010 (English)In: Journal of Pharmaceutical Sciences, ISSN 0022-3549, E-ISSN 1520-6017, Vol. 99, no 1, p. 219-226Article in journal (Refereed) Published
    Abstract [en]

    Pellets composed of the ceramic material Halloysite and microcrystalline cellulose were synthesized with the aim of producing a drug delivery vehicle for sustained release of the opioid Fentanyl with low risk for dose dumping at oral intake of the highly potent drug. Drug release profiles of intact and crushed pellets, to simulate swallowing without or with chewing, in pH 6.8, pH 1, and in 48% ethanol were recorded in order to replicate the conditions in the small intestines, in the stomach, as well as cointake of the drug with alcohol. The drug release was analyzed by employing the Weibull equation, which showed that the release profiles were either governed by fickian diffusion (intact pellets in pH 6.8 and in ethanol) or by diffusion in a fractal or disordered pore network (intact pellets in pH 1 and crushed pellets in all solutions). A sustained release for approximately 3-4 h was obtained in all studied solutions from intact pellets, whereas crushed pellets released the drug content during approximately 2-3 h. The finding that a sustained release profile could be obtained both in alcohol and after crushing of the pellets, shows that the ceramic carrier under investigation, at least to some extent, hampers dose dumping, and may thus be a promising material in future developments of new opioid containing oral dosage forms.

    National Category
    Other Materials Engineering
    Research subject
    Engineering Science with specialization in Nanotechnology and Functional Materials
    Identifiers
    urn:nbn:se:uu:diva-111786 (URN)10.1002/jps.21814 (DOI)000273151500016 ()19492338 (PubMedID)
    Available from: 2009-12-21 Created: 2009-12-21 Last updated: 2018-11-05Bibliographically approved
    2. Mechanically strong geopolymers offer new possibilities in treatment of chronic pain
    Open this publication in new window or tab >>Mechanically strong geopolymers offer new possibilities in treatment of chronic pain
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    2010 (English)In: Journal of Controlled Release, ISSN 0168-3659, E-ISSN 1873-4995, Vol. 146, no 3, p. 370-377Article in journal (Refereed) Published
    Abstract [en]

    We propose that a clay derived class of materials, known as geopolymers, may solve the problem of finding materials for controlled release with the right combination of properties necessary for a safe and sustained oral delivery of highly potent opioids. We show that the opioid Fentanyl, and its structurally similar sedative Zolpidem, can be embedded into metakaolin based geopolymer pellets to provide prolonged release dosage forms with mechanical strengths of the same order of magnitude as that of human teeth. The results presented in the current work may open up new opportunities for future development of drug delivery for high potency drugs employing high-strength and variable-pore-structure geopolymers and materials alike.

    National Category
    Engineering and Technology
    Identifiers
    urn:nbn:se:uu:diva-131243 (URN)10.1016/j.jconrel.2010.05.029 (DOI)000282398100014 ()20685295 (PubMedID)
    Available from: 2010-09-28 Created: 2010-09-28 Last updated: 2018-11-05Bibliographically approved
    3. Adjustable nanostructure of synthetic geopolymers enables tunable and sustained release of oxycodone
    Open this publication in new window or tab >>Adjustable nanostructure of synthetic geopolymers enables tunable and sustained release of oxycodone
    (English)Article in journal (Refereed) Submitted
    Identifiers
    urn:nbn:se:uu:diva-132372 (URN)
    Available from: 2010-10-19 Created: 2010-10-19 Last updated: 2011-01-13Bibliographically approved
    4. Formation and adhesion of biomimetic hydroxyapatite deposited on titanium substrates
    Open this publication in new window or tab >>Formation and adhesion of biomimetic hydroxyapatite deposited on titanium substrates
    2007 (English)In: Acta Biomaterialia, ISSN 1742-7061, Vol. 3, no 6, p. 980-984Article in journal (Refereed) Published
    Abstract [en]

    This study has been carried out to investigate the bioactivity of rutile and to deposit hydroxyapatite (HA) on heat-treated titanium through a biomimetic method. Biomimetic deposition of HA has gained large interest because of its low deposition temperature and good step coverage; however, it demands a substrate with bioactive properties. Commercially pure titanium is not bioactive but it can acquire bioactive properties through various surface treatments. In the present study, titanium plates were heat-treated at 800 °C to achieve rutile TiO2 surfaces. These samples were immersed in a phosphate-buffered saline solution for seven days in order to deposit a HA layer on the surface. The rutile TiO2 surfaces were found to be highly bioactive: after seven days of immersion, a layer of HA several micrometers thick covered the plates. The HA surfaces were confirmed by electron microscopy and X-ray diffraction. A scratch test was used to assess the adhesion of the HA coatings. This is a standard method to provide a measure of the coating-to-substrate adhesion and was found to be a useful method to test the thin HA coatings deposited on the bioactive surfaces. The critical pressure of the layer was estimated to be 2.4 ± 0.1 GPa.

    Keywords
    Hydroxyapatite, Bioactivity, Biomimetic deposition, Rutile, Adhesion
    National Category
    Engineering and Technology
    Identifiers
    urn:nbn:se:uu:diva-13067 (URN)10.1016/j.actbio.2007.03.006 (DOI)000250394000017 ()17512265 (PubMedID)
    Available from: 2008-06-09 Created: 2008-06-09 Last updated: 2018-02-08Bibliographically approved
    5. Structural change of biomimetic hydroxyapatite coatings due to heat treatment
    Open this publication in new window or tab >>Structural change of biomimetic hydroxyapatite coatings due to heat treatment
    2007 (English)In: Journal of Applied Biomaterials & Biomechanics, ISSN 1722-6899, Vol. 5, no 1, p. 23-27Article in journal (Refereed) Published
    Abstract [en]

    Biomimetic deposition of hydroxyapatite (HA) coatings on implants could be done for two reasons, one is to study their possible bioactivity, and one is to generate bioactive coatings on implants before implantation surgery to improve the osseointegration. Heat treatment of coated implants can be performed for several reasons, for example, to ensure coating sterility and to increase the adhesion. This paper describes the morphology and crystalline structure changes occurring due to the heat treatment of biomimetic HA coatings on rutile TiO2. Rutile TiO2 surfaces were produced on titanium (Ti) plates by heating at 800 C. Afterwards, these samples were immersed in a phosphate buffer saline solution for 7 days at 37 C in order to deposit HA coatings on their surfaces. These HA coatings were then either untreated or heat treated at 600 or 800 C for 1 hr. The coatings microstructural changes were studied using X-ray diffraction (XRD), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Cross-sectional TEM samples were produced using a sample preparation method based on focused ion beam microscopy (FIB). Rutile was found to be bioactive due to HA formation on the surface. The 600 C heat treatment of the HA coating changed its morphology, increased its grain size and also increased the porosity. At 800 C the coating was completely transformed to beta-TCP according to XRD. Sample preparation using FIB and TEM analysis proved to be a useful method for high-resolution analysis of biomimetic coatings in cross-section.

    Keywords
    microstructure, titanium, biomimetic coating, stability
    National Category
    Engineering and Technology
    Research subject
    Engineering Science with specialization in Nanotechnology and Functional Materials
    Identifiers
    urn:nbn:se:uu:diva-16172 (URN)000255726200003 ()
    Available from: 2008-06-09 Created: 2009-02-26 Last updated: 2018-02-08Bibliographically approved
    6. Assessing Surface Area Evolution during Biomimetic Growth of Hydroxyapatite Coatings
    Open this publication in new window or tab >>Assessing Surface Area Evolution during Biomimetic Growth of Hydroxyapatite Coatings
    2009 (English)In: Langmuir, ISSN 0743-7463, E-ISSN 1520-5827, Vol. 25, no 3, p. 1292-1295Article in journal (Refereed) Published
    Abstract [en]

    The surface area of biomimetically deposited hydroxyapatite (HA) coatings on metallic implants is important for the biological performance of the implant. Thus, a nondestructive method of assessing this quantity directly on the solid substrate would be highly valuable. The objective of this study was to develop such a method and for the first time assess the evolution of surface area of HA during biomimetic growth. The surface area of a TiO2-covered titanium substrate was measured prior to and following the biomimetic coating deposition using Ar gas adsorption at 77 K. The presence of HA on the surface was verified with scanning electron microscopy and X-ray diffraction. The specific surface area of the coating was found to increase linearly during 1 week of deposition at a rate of ∼100 cm2 day−1 (g substrate)−1. The presented method may be used as a tool for studying the evolution in surface area of coatings on solid substrates during biomimetic deposition or other growth processes.

    National Category
    Engineering and Technology
    Identifiers
    urn:nbn:se:uu:diva-88439 (URN)10.1021/la803520k (DOI)000262827400007 ()19115807 (PubMedID)
    Available from: 2009-02-02 Created: 2009-02-02 Last updated: 2018-02-08Bibliographically approved
    7. Multifunctional implant coatings providing possibilities for fast antibiotics loading with subsequent slow release
    Open this publication in new window or tab >>Multifunctional implant coatings providing possibilities for fast antibiotics loading with subsequent slow release
    Show others...
    2009 (English)In: Journal of materials science. Materials in medicine, ISSN 0957-4530, E-ISSN 1573-4838, Vol. 20, no 9, p. 1859-1867Article in journal (Refereed) Published
    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.

    National Category
    Engineering and Technology Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-122095 (URN)10.1007/s10856-009-3749-6 (DOI)000268786400010 ()19399593 (PubMedID)
    Available from: 2010-04-06 Created: 2010-04-06 Last updated: 2018-02-08Bibliographically approved
    8. Co-loading of bisphosphonates and antibiotics to a biomimetic hydroxyapatite coating
    Open this publication in new window or tab >>Co-loading of bisphosphonates and antibiotics to a biomimetic hydroxyapatite coating
    2011 (English)In: Biotechnology letters, ISSN 0141-5492, E-ISSN 1573-6776, Vol. 33, no 6, p. 1265-1268Article in journal (Refereed) Published
    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.

    National Category
    Nano Technology Medical Biotechnology
    Research subject
    Engineering Science with specialization in Nanotechnology and Functional Materials
    Identifiers
    urn:nbn:se:uu:diva-145824 (URN)10.1007/s10529-011-0542-7 (DOI)000291655200027 ()21287232 (PubMedID)
    Available from: 2011-02-11 Created: 2011-02-11 Last updated: 2018-02-08Bibliographically approved
    9. In vitro characterization of bioactive titanium dioxide/hydroxyapatite surfaces functionalized with BMP-2
    Open this publication in new window or tab >>In vitro characterization of bioactive titanium dioxide/hydroxyapatite surfaces functionalized with BMP-2
    Show others...
    2009 (English)In: Journal of biomedical materials research. Part B, Applied biomaterials, ISSN 1552-4981, Vol. 91B, no 2, p. 780-787Article in journal (Refereed) Published
    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.

    Keywords
    biomimetic hydroxyapatite, growth factors, BMP-2, anatase titanium dioxide, mesenchymal stem cells, differentiation, viability, morphology
    National Category
    Engineering and Technology
    Research subject
    Engineering Science with specialization in Nanotechnology and Functional Materials
    Identifiers
    urn:nbn:se:uu:diva-108680 (URN)10.1002/jbm.b.31456 (DOI)000270868600034 ()19582842 (PubMedID)
    Available from: 2009-09-26 Created: 2009-09-26 Last updated: 2018-02-08Bibliographically approved
    10. In Vivo Evaluation of Functionalized Biomimetic Hydroxyapatite for Local Delivery of Active Agents
    Open this publication in new window or tab >>In Vivo Evaluation of Functionalized Biomimetic Hydroxyapatite for Local Delivery of Active Agents
    Show others...
    2011 (English)In: Journal of Biomaterials and Nanobiotechnology, ISSN 2158-7027, 2158-7043, Vol. 2, no 2, p. 149-154Article in journal (Refereed) Published
    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.

    National Category
    Engineering and Technology Polymer Chemistry
    Research subject
    Engineering Science with specialization in Materials Science; Engineering Science with specialization in Nanotechnology and Functional Materials; Chemistry with specialization in Polymer Chemistry
    Identifiers
    urn:nbn:se:uu:diva-156129 (URN)10.4236/jbnb.2011.22019 (DOI)
    Funder
    Swedish Research Council
    Available from: 2011-07-11 Created: 2011-07-11 Last updated: 2018-02-08Bibliographically approved
    11. A novel method for local administration of strontium from implant surfaces
    Open this publication in new window or tab >>A novel method for local administration of strontium from implant surfaces
    2010 (English)In: Journal of materials science. Materials in medicine, ISSN 0957-4530, E-ISSN 1573-4838, Vol. 21, no 5, p. 1605-1609Article in journal (Refereed) Published
    Abstract [en]

    This study proves that a film of Strontianite (SrCO(3)) successfully can be formed on a bioactive surface of sodium titanate when exposed to a strontium acetate solution. This Strontianite film is believed to enable local release of strontium ions from implant surfaces and thus stimulate bone formation in vivo. Depending on the method, different types of films were achieved with different release rates of strontium ions, and the results points at the possibility to tailor the rate and amount of strontium that is to be released from the surface. Strontium has earlier been shown to be highly involved in the formation of new bone as it stimulates the replication of osteoblasts and decreases the activity of osteoclasts. The benefit of strontium has for example been proved in studies where the number of vertebral compression fractures in osteoporotic persons was drastically reduced in patients receiving therapeutical doses of strontium. Therefore, it is here suggested that the bone healing process around an implant may be improved if strontium is administered locally at the site of the implant. The films described in this paper were produced by a simple immersion process where alkali treated titanium was exposed to an aqueous solution containing strontium acetate. By heating the samples at different times during the process, different release rates of strontium ions were achieved when the samples were exposed to simulated body fluid. The strontium containing films also promoted precipitation of bone like apatite when exposed to a simulated body fluid.

    National Category
    Engineering and Technology
    Identifiers
    urn:nbn:se:uu:diva-125407 (URN)10.1007/s10856-010-4022-8 (DOI)000277603000023 ()20162327 (PubMedID)
    Available from: 2010-05-18 Created: 2010-05-18 Last updated: 2018-02-08Bibliographically approved
  • 9.
    Forsgren, Johan
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Andersson, Mattias
    Nilsson, Peter
    Mihranyan, Albert
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Mesoporous Calcium Carbonate as a Phase Stabilizer of Amorphous Celecoxib - An Approach to Increase the Bioavailability of Poorly Soluble Pharmaceutical Substances.2013In: Advanced healthcare materials, ISSN 2192-2640, Vol. 2, no 11, p. 1469-1476Article in journal (Refereed)
    Abstract [en]

    The bioavailability of crystalline pharmaceutical substances is often limited by their poor aqueous solubility but it can be improved by formulating the active substance in the amorphous state that is featured with a higher apparent solubility. Although the possibility of stabilizing amorphous drugs inside nano-sized pores of carbon nanotubes and ordered mesoporous silica has been shown, no conventional pharmaceutical excipients have so far been shown to possess this property. This study demonstrates the potential of using CaCO3 , a widely used excipient in oral drug formulations, to stabilize the amorphous state of active pharmaceutical ingredients, in particular celecoxib. After incorporation of celecoxib in the vaterite particles, a five to sixfold enhancement in apparent solubility of celecoxib is achieved due to pore-induced amorphization. To eliminate the possibility of uncontrolled phase transitions, the vaterite particles were stored in an inert atmosphere at 5 °C throughout the study. Also, to demonstrate that the amorphization effect was indeed associated with vaterite mesopores, accelerated stress conditions of 100% relative humidity was employed to impose transition from mesoporous vaterite to an essentially non-porous aragonite phase of CaCO3 , which shows only limited amorphization ability. Further, an improvement in solubility was also confirmed for ketoconazole when formulated with the mesoporous vaterite. Synthesis of the carrier particles and the incorporation of the active substances were carried out simultaneously in a one-step procedure, enabling easy fabrication. These results represent a promising approach to achieve enhanced bioavailability in new formulations of Type II BCS drugs.

  • 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.
    Forsgren, Johan
    et al.
    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 method for local administration of strontium from implant surfaces2010In: Journal of materials science. Materials in medicine, ISSN 0957-4530, E-ISSN 1573-4838, Vol. 21, no 5, p. 1605-1609Article in journal (Refereed)
    Abstract [en]

    This study proves that a film of Strontianite (SrCO(3)) successfully can be formed on a bioactive surface of sodium titanate when exposed to a strontium acetate solution. This Strontianite film is believed to enable local release of strontium ions from implant surfaces and thus stimulate bone formation in vivo. Depending on the method, different types of films were achieved with different release rates of strontium ions, and the results points at the possibility to tailor the rate and amount of strontium that is to be released from the surface. Strontium has earlier been shown to be highly involved in the formation of new bone as it stimulates the replication of osteoblasts and decreases the activity of osteoclasts. The benefit of strontium has for example been proved in studies where the number of vertebral compression fractures in osteoporotic persons was drastically reduced in patients receiving therapeutical doses of strontium. Therefore, it is here suggested that the bone healing process around an implant may be improved if strontium is administered locally at the site of the implant. The films described in this paper were produced by a simple immersion process where alkali treated titanium was exposed to an aqueous solution containing strontium acetate. By heating the samples at different times during the process, different release rates of strontium ions were achieved when the samples were exposed to simulated body fluid. The strontium containing films also promoted precipitation of bone like apatite when exposed to a simulated body fluid.

  • 15.
    Forsgren, Johan
    et al.
    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 surface modification enabling local administration of strontium from implants2010Conference paper (Refereed)
  • 16.
    Forsgren, Johan
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Frykstrand, Sara
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Grandfield, Kathryn
    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.
    Strømme, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    A Template-Free, Ultra-Adsorbing, High Surface Area Carbonate Nanostructure2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 7, p. e68486-Article in journal (Refereed)
    Abstract [en]

    We report the template-free, low-temperature synthesis of a stable, amorphous, and anhydrous magnesium carbonate nanostructure with pore sizes below 6 nm and a specific surface area of ~ 800 m2 g−1, substantially surpassing the surface area of all previously described alkali earth metal carbonates. The moisture sorption of the novel nanostructure is featured by a unique set of properties including an adsorption capacity ~50% larger than that of the hygroscopic zeolite-Y at low relative humidities and with the ability to retain more than 75% of the adsorbed water when the humidity is decreased from 95% to 5% at room temperature. These properties can be regenerated by heat treatment at temperatures below 100°C.The structure is foreseen to become useful in applications such as humidity control, as industrial adsorbents and filters, in drug delivery and catalysis.

  • 17.
    Forsgren, Johan
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Frykstrand, Sara
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Zhang, Peng
    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.
    Porous alkali earth metal carbonates as enhancers of solubility for poorly soluble drugs2015In: Nanotechnologies in Drug Delivery, London 2015, 2015Conference paper (Refereed)
  • 18.
    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.
    Hoess, Andreas
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Ott, Marjam
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    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.
    A Soluble Strontium Carbonate Implant Coating for Local and Targeted Cell Stimulation2011In: MRS Spring Meeeting 2011, 2011Conference paper (Refereed)
  • 19.
    Forsgren, Johan
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Jämstorp, Erik
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Bredenberg, Susanne
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    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.
    A ceramic drug delivery vehicle for oral administration of highly potent opioids2010In: Journal of Pharmaceutical Sciences, ISSN 0022-3549, E-ISSN 1520-6017, Vol. 99, no 1, p. 219-226Article in journal (Refereed)
    Abstract [en]

    Pellets composed of the ceramic material Halloysite and microcrystalline cellulose were synthesized with the aim of producing a drug delivery vehicle for sustained release of the opioid Fentanyl with low risk for dose dumping at oral intake of the highly potent drug. Drug release profiles of intact and crushed pellets, to simulate swallowing without or with chewing, in pH 6.8, pH 1, and in 48% ethanol were recorded in order to replicate the conditions in the small intestines, in the stomach, as well as cointake of the drug with alcohol. The drug release was analyzed by employing the Weibull equation, which showed that the release profiles were either governed by fickian diffusion (intact pellets in pH 6.8 and in ethanol) or by diffusion in a fractal or disordered pore network (intact pellets in pH 1 and crushed pellets in all solutions). A sustained release for approximately 3-4 h was obtained in all studied solutions from intact pellets, whereas crushed pellets released the drug content during approximately 2-3 h. The finding that a sustained release profile could be obtained both in alcohol and after crushing of the pellets, shows that the ceramic carrier under investigation, at least to some extent, hampers dose dumping, and may thus be a promising material in future developments of new opioid containing oral dosage forms.

  • 20.
    Forsgren, Johan
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Lilja, Mirjam
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Åstrand, Maria
    Sandvik AB.
    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.
    Welch, Ken
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Photocatalytic and antimicrobial properties of a TiO2 implant coating deposited through cathodic arc evaporation2012In: European Cells and Materials, ISSN 1473-2262, E-ISSN 1473-2262, Vol. 23, no Suppl. 5, p. 36-Article in journal (Refereed)
  • 21.
    Forsgren, Johan
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Lilja, Mirjam
    Nanoteknologi och funktionella material, Nanotechnology and Functional Materials.
    Åstrand, Maria
    Sandvik Sverige AB.
    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.
    Welch, Ken
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Photocatalytic and antimicrobial properties of a TiO2 implant coating deposited through cathodic arc evaporation2012In: Scandinavian Society of Biomaterials, Uppsala, Sweden, May 2012, 2012Conference paper (Refereed)
  • 22.
    Forsgren, Johan
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Paz, Loli
    Vigo University, Spain.
    Léon, Betty
    Vigo University, Spain.
    Engqvist, Håkan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    A rapid method to improve the biological response to titanium by laser induced conversion of Ti4+ to Ti3+ sites in titanium oxide surfaces.2010In: Sicot/Sirot - Ortopediveckan 2010, 2010Conference paper (Refereed)
  • 23.
    Forsgren, Johan
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Paz, María Dolores
    León, Betty
    Engqvist, Håkan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Laser induced surface structuring and ion conversion in the surface oxide of titanium: possible implications for the wetability of laser treated implants.2013In: Journal of materials science. Materials in medicine, ISSN 0957-4530, E-ISSN 1573-4838, Vol. 24, no 1, p. 11-15Article in journal (Refereed)
    Abstract [en]

    In the present study, commercially pure titanium was irradiated with UV-light with varying wavelengths using a Q-switched Nd:YAG-laser. This was performed in order to investigate if a laser treatment can be employed to rapidly introduce hydrophilic properties to titanium surfaces, which is believed to facilitate protein adsorption and cell attachment. It was demonstrated that irradiation with 355 nm light (10 Hz, 90 mJ/shot) for 1 min or more caused an ion conversion of Ti(4+) to Ti(3+) sites in the surface oxide which lead to an increase in hydrophilicity of the surface. Furthermore, shorter irradiation times at 355 nm caused a surface structuring that gave rise to an unexpected and unstable hydrophobic state at the surface. Irradiation with 266 nm light (10 Hz, 40 mJ/shot) did not introduce any ion conversion in the surface oxide, nor did it give rise to any hydrophobicity of the surface.

  • 24.
    Forsgren, Johan
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Pedersen, Christian
    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.
    Sustained Drug Release from Mesoporous Geopolymers2011In: MRS Spring Meeting and Exhibit 2011, 2011Conference paper (Refereed)
  • 25.
    Forsgren, Johan
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Pedersen, Christian
    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.
    Synthetic geopolymers for controlled delivery of oxycodone: Adjustable and nanostructured porosity enables tunable and sustained drug release2011In: PLoS ONE, ISSN 1932-6203, Vol. 6, no 3, p. e17759-Article in journal (Refereed)
    Abstract [en]

    In this article we for the first time present a fully synthetic mesoporous geopolymer drug carrier for controlled release of opioids. Nanoparticulate precursor powders with different Al/Si-ratios were synthesized by a sol-gel route and used in the preparation of different geopolymers, which could be structurally tailored by adjusting the Al/Si-ratio and the curing temperatures. In particular, it was shown that the pore sizes of the geopolymers decreased with increasing Al/Si ratio and that completely mesoporous geopolymers could be produced from precursor particles with the Al/Si ratio 2:1. The mesoporosity was shown to be associated with a sustained and linear in vitro release profile of the opioid oxycodone. A clinically relevant release period of about 12 h was obtained by adjusting the size of the pellets. The easily fabricated and tunable geopolymers presented in this study constitute a novel approach in the development of controlled release formulations, not only for opioids, but whenever the clinical indication is best treated with a constant supply of drugs and when the mechanical stability of the delivery vehicle is crucial.

  • 26.
    Forsgren, Johan
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Svahn, Fredrik
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Jarmar, Tobias
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Engqvist, Håkan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Formation and adhesion of biomimetic hydroxyapatite deposited on titanium substrates2007In: Acta Biomaterialia, ISSN 1742-7061, Vol. 3, no 6, p. 980-984Article in journal (Refereed)
    Abstract [en]

    This study has been carried out to investigate the bioactivity of rutile and to deposit hydroxyapatite (HA) on heat-treated titanium through a biomimetic method. Biomimetic deposition of HA has gained large interest because of its low deposition temperature and good step coverage; however, it demands a substrate with bioactive properties. Commercially pure titanium is not bioactive but it can acquire bioactive properties through various surface treatments. In the present study, titanium plates were heat-treated at 800 °C to achieve rutile TiO2 surfaces. These samples were immersed in a phosphate-buffered saline solution for seven days in order to deposit a HA layer on the surface. The rutile TiO2 surfaces were found to be highly bioactive: after seven days of immersion, a layer of HA several micrometers thick covered the plates. The HA surfaces were confirmed by electron microscopy and X-ray diffraction. A scratch test was used to assess the adhesion of the HA coatings. This is a standard method to provide a measure of the coating-to-substrate adhesion and was found to be a useful method to test the thin HA coatings deposited on the bioactive surfaces. The critical pressure of the layer was estimated to be 2.4 ± 0.1 GPa.

  • 27.
    Forsgren, Johan
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Svahn, Fredrik
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Jarmar, Tobias
    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.
    Structural change of biomimetic hydroxyapatite coatings due to heat treatment2007In: Journal of Applied Biomaterials & Biomechanics, ISSN 1722-6899, Vol. 5, no 1, p. 23-27Article in journal (Refereed)
    Abstract [en]

    Biomimetic deposition of hydroxyapatite (HA) coatings on implants could be done for two reasons, one is to study their possible bioactivity, and one is to generate bioactive coatings on implants before implantation surgery to improve the osseointegration. Heat treatment of coated implants can be performed for several reasons, for example, to ensure coating sterility and to increase the adhesion. This paper describes the morphology and crystalline structure changes occurring due to the heat treatment of biomimetic HA coatings on rutile TiO2. Rutile TiO2 surfaces were produced on titanium (Ti) plates by heating at 800 C. Afterwards, these samples were immersed in a phosphate buffer saline solution for 7 days at 37 C in order to deposit HA coatings on their surfaces. These HA coatings were then either untreated or heat treated at 600 or 800 C for 1 hr. The coatings microstructural changes were studied using X-ray diffraction (XRD), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Cross-sectional TEM samples were produced using a sample preparation method based on focused ion beam microscopy (FIB). Rutile was found to be bioactive due to HA formation on the surface. The 600 C heat treatment of the HA coating changed its morphology, increased its grain size and also increased the porosity. At 800 C the coating was completely transformed to beta-TCP according to XRD. Sample preparation using FIB and TEM analysis proved to be a useful method for high-resolution analysis of biomimetic coatings in cross-section.

  • 28.
    Frykstrand, Sara
    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.
    Cheung, Ocean
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Zhang, Peng
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Hong, Jaan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Strømme, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Ferraz, Natalia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Study of mesoporous magnesium carbonate in contact with whole human blood2016In: RSC Advances, ISSN 2046-2069, E-ISSN 2046-2069, Vol. 6, no 58, p. 52810-52816Article in journal (Refereed)
    Abstract [en]

    The interaction of mesoporours magnesium carbonate (Upsalite) particles (50-100 mm) with human whole blood was investigated using an in vitro loop model and the effect on the complement system, blood coagulation and red blood cell lysis was assessed. The removal of Ca2+ by Upsalite and the possible exchange with and/or release of Mg2+ were explored as well. Upsalite was found to present anticoagulant properties, most probably due to the uptake of Ca2+ by the particles. No hemolytic activity was detected at Upsalite concentrations up to 1 mg ml(-1). Moderate to high levels of C3a and sC5b-9 were observed for Upsalite, however such levels were statistically different from the negative control only when the particle concentrations were 0.25 mg ml(-1) and 1.0 mg ml(-1), respectively. The presented findings are promising for the future development of mesoporous magnesium carbonate-based materials for biomedical applications.

  • 29.
    Frykstrand, Sara
    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.
    Mihranyan, Albert
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Ferraz, Natalia
    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.
    Synthesis and potential of Upsalite®: a mesoporous magnesium carbonate synthesized without surfactants2015In: Fourth International Conference on Multifunctional, Hybrid and Nanomaterials: Hybrid Materials 2015, Stiges, 2015, p. P1.225-Conference paper (Refereed)
  • 30.
    Frykstrand, Sara
    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.
    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.
    On the pore forming mechanism of Upsalite, a micro- and mesoporous magnesium carbonate2014In: Microporous and Mesoporous Materials, ISSN 1387-1811, E-ISSN 1873-3093, Vol. 190, p. 99-104Article in journal (Refereed)
    Abstract [en]

    This work analyzes the pore forming mechanism and stability of Upsalite; an extraordinary moisture absorbing, high-surface area magnesium carbonate powder synthesised without the use of surfactants as pore forming agents. The pores in Upsalite were found to be created in a two-step process where the first step includes the formation of micropores by solvent evaporation and release of physically bound carbon dioxide, acting as an in-situ pore-forming template. In the second step, the micropores expand to mesopores due to partial decomposition of organic groups on the surface of the pore walls when the material is stored in air at moderate temperatures (70 °C). The resulting material has a narrow pore size distribution centered at 5 nm, and the amorphous structure is stable upon storage in a humid atmosphere.

    It was further shown that calcination at temperatures above 250 °C is required for complete removal of the organic surface groups in Upsalite. Prior to calcination, the organic groups present in the material act as barriers hindering water to induce crystallization of the bulk material. After calcination, however, Upsalite crystallizes into nesquehonite when stored at 100 % relative humidity for several days. The results presented herein are expected to be useful for the development of novel surfactant-free synthesis routes of porous materials as well as for the understanding of the long-term performance of such materials.

  • 31.
    Frykstrand, Sara
    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.
    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.
    On the use of gas as a pore forming agent in mesoporous materials2014Conference paper (Other academic)
  • 32.
    Frykstrand, Sara
    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.
    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.
    The formation of UpsaliteTM: A template-free micro- and mesoporous amorphous magnesium carbonate2013Conference paper (Refereed)
  • 33.
    Frykstrand, Sara
    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.
    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.
    Upsalite®: A template-free micro- and  mesoporous amorphous magnesium carbonate2014Conference paper (Refereed)
  • 34.
    Frykstrand, Sara
    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.
    Strømme, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Ferraz, Natalia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Cytotoxicity and in vivo irritation of Upsalite®, a mesoporous magnesium carbonate 2014Conference paper (Refereed)
  • 35.
    Frykstrand, Sara
    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.
    Zhang, Peng
    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.
    Upsaliteᵀᴹ - A Novel Magnesium Carbonate With A Mesoporous Structure Promising For Biomedical Applications2014Conference paper (Refereed)
  • 36.
    Frykstrand, Sara
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Strietzel, Christian
    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.
    Ångström, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström.
    Potin, Valerie
    Strømme, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Synthesis, electron microscopy and X-ray characterization of oxymagnesite, MgO∙2MgCO3, formed from amorphous magnesium carbonate2014In: CrystEngComm, ISSN 1466-8033, E-ISSN 1466-8033, Vol. 16, no 47, p. 10837-10844Article in journal (Refereed)
    Abstract [en]

    At present, the peculiar compound called oxymagnesite, MgO center dot 2MgCO(3), an intermediate formed during thermal decomposition of hydrated magnesium carbonates, has only been described a handful of times without a distinct description of its formation or morphology. In the current work we present the first scanning and transmission electron microscopy images of an oxymagnesite crystal together with its crystallographic data. Oxymagnesite was synthesized in a controlled manner via decomposition of amorphous magnesium carbonates (AMCs) subjected to varying relative humidity. We show that oxymagnesite is formed only when AMC is hydrated above a certain level, which we attribute to structural inequivalence between CO3 groups induced by water in AMC subjected to high humidity resulting in a weakening of some of the Mg-CO3 bonds. The study provides an understanding of the conditions needed for oxymagnesite formation and shows how hydrated AMCs can be used as precursors of different types of magnesium carbonates.

  • 37.
    Frykstrand, Sara
    et al.
    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.
    Forsgren, Johan
    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.
    The Formation and Characterization of A New Type Of Carbonate Structure2013In: , 2013, p. 1-Conference paper (Other academic)
  • 38.
    Frykstrand, Sara
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Zhang, Peng
    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.
    Mihranyan, Albert
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Ferraz, Natalia
    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.
    The surfactant-free synthesis of Upsalite®, a mesoporous magnesium carbonate and its use as a solubility enhancer for poorly soluble drugs: -2014Conference paper (Refereed)
  • 39.
    Gómez de la Torre, Johan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Embrace Chaos, Be Observant & Expect the Unexpected2013In: Lost and Found, TedX, Munchen September 2013 / [ed] TedX, Munchen: TedX , 2013, p. 10068-Conference paper (Refereed)
  • 40.
    Jämstorp, Erik
    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.
    Bredenberg, Susanne
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    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.
    Mechanically strong geopolymers offer new possibilities in treatment of chronic pain2010In: Journal of Controlled Release, ISSN 0168-3659, E-ISSN 1873-4995, Vol. 146, no 3, p. 370-377Article in journal (Refereed)
    Abstract [en]

    We propose that a clay derived class of materials, known as geopolymers, may solve the problem of finding materials for controlled release with the right combination of properties necessary for a safe and sustained oral delivery of highly potent opioids. We show that the opioid Fentanyl, and its structurally similar sedative Zolpidem, can be embedded into metakaolin based geopolymer pellets to provide prolonged release dosage forms with mechanical strengths of the same order of magnitude as that of human teeth. The results presented in the current work may open up new opportunities for future development of drug delivery for high potency drugs employing high-strength and variable-pore-structure geopolymers and materials alike.

  • 41.
    Lilja, Mirjam
    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.
    Welch, Ken
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Åstrand, Maria
    Sandvik AB.
    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.
    Photocatalytic and antimicrobial properties of surgical implant coatings of titanium dioxide deposited though cathodic arc evaporation2012In: Biotechnology letters, ISSN 0141-5492, E-ISSN 1573-6776, Vol. 41, no 6, p. 740-746Article in journal (Refereed)
    Abstract [en]

    Nanostructured crystalline titaniumdioxide coatings deposited by cathodic arc evaporated on titanium grade five medical implant substrates were demonstrated to exhibit UV-induced photocatalytic activity that can be utilized to provide bactericidal effects against Staphylococcus epidermidis. The photocatalytic activity of the coatings was confirmedvia degradation of Rhodamine B under UV illumination.A 90 %reduction of viable bacteria was achieved in a clinically suitable time of only 2 min with a UVdose of 2.4 J delivered at 365 nm. These results areencouraging for the development of antimicrobialsurfaces in orthopedics and dentistry in order to prevent or treat post-surgical infections.

  • 42.
    Mellgren, Torbjörn
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Forsgren, Johan
    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.
    Persson, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    A self-hardening biodegradable cement as a drug delivery vehicle2012In: European Cells and Materials, ISSN 1473-2262, E-ISSN 1473-2262, Vol. 23, no S5, p. 51-51Article in journal (Refereed)
  • 43.
    Mihranyan, Albert
    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.
    Maria, Strømme
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Influence of regioselective TEMPO oxidation of highly crystalline nanocellulose fibers on drug release and stability2012In: 47th AAPS Arden Conference, West Point, 2012Conference paper (Refereed)
  • 44.
    Mihranyan, Albert
    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.
    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.
    Assessing Surface Area Evolution during Biomimetic Growth of Hydroxyapatite Coatings2009In: Langmuir, ISSN 0743-7463, E-ISSN 1520-5827, Vol. 25, no 3, p. 1292-1295Article in journal (Refereed)
    Abstract [en]

    The surface area of biomimetically deposited hydroxyapatite (HA) coatings on metallic implants is important for the biological performance of the implant. Thus, a nondestructive method of assessing this quantity directly on the solid substrate would be highly valuable. The objective of this study was to develop such a method and for the first time assess the evolution of surface area of HA during biomimetic growth. The surface area of a TiO2-covered titanium substrate was measured prior to and following the biomimetic coating deposition using Ar gas adsorption at 77 K. The presence of HA on the surface was verified with scanning electron microscopy and X-ray diffraction. The specific surface area of the coating was found to increase linearly during 1 week of deposition at a rate of ∼100 cm2 day−1 (g substrate)−1. The presented method may be used as a tool for studying the evolution in surface area of coatings on solid substrates during biomimetic deposition or other growth processes.

  • 45.
    Muelhopt, Sonja
    et al.
    Karlsruhe Inst Technol, Inst Tech Chem, D-76131 Karlsruhe, Germany.
    Diabate, Silvia
    Karlsruhe Inst Technol, Inst Toxicol & Genet, D-76131 Karlsruhe, Germany.
    Dilger, Marco
    Karlsruhe Inst Technol, Inst Toxicol & Genet, D-76131 Karlsruhe, Germany.
    Adelhelm, Christel
    Karlsruhe Inst Technol, Inst Appl Mat, D-76131 Karlsruhe, Germany.
    Anderlohr, Christopher
    Karlsruhe Inst Technol, Inst Tech Thermodynam & Refrigerat ITTK, D-76131 Karlsruhe, Germany.
    Bergfeldt, Thomas
    Karlsruhe Inst Technol, Inst Appl Mat, D-76131 Karlsruhe, Germany.
    Gómez de la Torre, Johan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Jiang, Yunhong
    Univ Bath, Dept Architecture & Civil Engn, Claverton Down, Bath BA2 7AY, Avon, England.
    Valsami-Jones, Eugenia
    Univ Birmingham, Sch Geog Earth & Environm Sci, Birmingham B15 2TT, W Midlands, England.
    Langevin, Dominique
    Univ Paris Saclay, Univ Paris Sud 11, CNRS UMR 8502, Lab Phys Solides, F-91190 St Aubin, France.
    Lynch, Iseult
    Univ Birmingham, Sch Geog Earth & Environm Sci, Birmingham B15 2TT, W Midlands, England.
    Mahon, Eugene
    Univ Coll Dublin, Sch Chem & Chem Biol, Ctr BioNano Interact, Dublin 4, Ireland.
    Nelissen, Inge
    Flemish Inst Technol Res VITO, Dept Hlth, B-2400 Mol, Belgium.
    Piella, Jordi
    CSIC, Catalan Inst Nanosci & Nanotechnol ICN2, Barcelona 08036, Spain;Barcelona Inst Sci & Technol, Barcelona 08036, Spain.
    Puntes, Victor
    CSIC, Catalan Inst Nanosci & Nanotechnol ICN2, Barcelona 08036, Spain;Barcelona Inst Sci & Technol, Barcelona 08036, Spain.
    Ray, Sikha
    Karlsruhe Inst Technol, STN, D-76131 Karlsruhe, Germany.
    Schneider, Reinhard
    Karlsruhe Inst Technol, LEM, D-76131 Karlsruhe, Germany.
    Wilkins, Terry
    Univ Leeds, Sch Chem & Proc Engn, Fac Engn, Leeds LS2 9JT, W Yorkshire, England.
    Weiss, Carsten
    Karlsruhe Inst Technol, Inst Toxicol & Genet, D-76131 Karlsruhe, Germany.
    Paur, Hanns-Rudolf
    Karlsruhe Inst Technol, Inst Tech Chem, D-76131 Karlsruhe, Germany.
    Characterization of Nanoparticle Batch-To-Batch Variability2018In: NANOMATERIALS, ISSN 2079-4991, Vol. 8, no 5, article id 311Article in journal (Refereed)
    Abstract [en]

    A central challenge for the safe design of nanomaterials (NMs) is the inherent variability of NM properties, both as produced and as they interact with and evolve in, their surroundings. This has led to uncertainty in the literature regarding whether the biological and toxicological effects reported for NMs are related to specific NM properties themselves, or rather to the presence of impurities or physical effects such as agglomeration of particles. Thus, there is a strong need for systematic evaluation of the synthesis and processing parameters that lead to potential variability of different NM batches and the reproducible production of commonly utilized NMs. The work described here represents over three years of effort across 14 European laboratories to assess the reproducibility of nanoparticle properties produced by the same and modified synthesis routes for four of the OECD priority NMs (silica dioxide, zinc oxide, cerium dioxide and titanium dioxide) as well as amine-modified polystyrene NMs, which are frequently employed as positive controls for nanotoxicity studies. For 46 different batches of the selected NMs, all physicochemical descriptors as prioritized by the OECD have been fully characterized. The study represents the most complete assessment of NMs batch-to-batch variability performed to date and provides numerous important insights into the potential sources of variability of NMs and how these might be reduced.

  • 46. 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)
  • 47. 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)
  • 48.
    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.

  • 49.
    Pochard, Isabelle
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials. Univ Bourgogne, CNRS, Lab Interdisciplinaire Carnot Bourgogne ICB, UMR 6303, Dijon, France.
    Frykstrand, Sara
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Ahlström, Olle
    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.
    Strømme, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Water and ion transport in ultra-adsorbing porous magnesium carbonate studied by dielectric spectroscopy2014In: Journal of Applied Physics, ISSN 0021-8979, E-ISSN 1089-7550, Vol. 115, no 4, article id 044306Article in journal (Refereed)
    Abstract [en]

    Porous materials are used in application areas ranging from drug and vaccine delivery, medical implants, molecular sieves and cosmetics to catalysis and humidity control. In the present work, we employed an alternative approach to gain in-depth understanding about water interaction properties in such materials by the use of dielectric spectroscopy and thereby show that it is possible to obtain information that is not accessible from the more commonly employed water interaction analysis techniques. Specifically, the complex dielectric response of Upsalite, a novel, super-hydroscopic, high-surface area, porous magnesium carbonate material was measured in isothermal frequency scans between 10−3 and 106 Hz at controlled relative humidity (RH). We found the dielectric constant of the dry material to be 1.82. The ratio of bound to free water present in Upsalite after adsorption at room temperature was found to be high irrespective of the surrounding humidity with values ranging from ∼67% to ∼90%. We further found that OH ions are the charge carriers responsible for the electrode polarization observed in the dielectric response and that the amount of these ions that are free to move in the material corresponds to a concentration of the order of 1–10 μmol l−1 independent of RH. Finally, the OH diffusion coefficient displayed a drastic decrease with decreasing RH, typical of transport in unsaturated conditions. The presented results provide detailed insight about water interactions in the novel water adsorbing material under study and it is foreseen that the employed analysis methods can be used to evaluate other types of moisture adsorbing materials as well as the movement of functional species in the pores of inorganic drug delivery materials and materials tailored for adsorption of harmful charged species.

  • 50.
    Strömme, Maria
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Frykstrand, Sara
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Zhang, Peng
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Lindh, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Ferraz, Natalia
    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.
    Sjödin, Martin
    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.
    From porous nanocellulose composites in life science and energy storage to mesoporous magnesium carbonate as drug solubility enhancer 2015In: Fourth International Conference on Multifunctional, Hybrid and Nanomaterials: Hybrid Materials 2015 / [ed] Elsevier, 2015, Vol. 4, p. OPC.07.07-Conference paper (Refereed)
12 1 - 50 of 55
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