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In vitro characterization of bioactive titanium dioxide/hydroxyapatite surfaces functionalized with BMP-2
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Materials Chemistry, Polymer Chemistry. (polymerkemi)
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, Nanotechnology and Functional Materials.
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
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2009 (English)In: Journal of biomedical materials research. Part B, Applied biomaterials, ISSN 1552-4981, Vol. 91B, no 2, 780-787 p.Article 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.

Place, publisher, year, edition, pages
2009. Vol. 91B, no 2, 780-787 p.
Keyword [en]
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: urn:nbn:se:uu:diva-108680DOI: 10.1002/jbm.b.31456ISI: 000270868600034PubMedID: 19582842OAI: oai:DiVA.org:uu-108680DiVA: diva2:240265
Available from: 2009-09-26 Created: 2009-09-26 Last updated: 2016-11-30Bibliographically approved
In thesis
1. Functional Ceramics in Biomedical Applications: On the Use of Ceramics for Controlled Drug Release and Targeted Cell Stimulation
Open this publication in new window or tab >>Functional Ceramics in Biomedical Applications: On the Use of Ceramics for Controlled Drug Release and Targeted Cell Stimulation
2010 (English)Doctoral 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.

 

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2010. 99 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 780
Keyword
Controlled release, geopolymer, sol-gel, opioid, oral administration, oral dosage form, implant, titanium, hydroxyapatite, infection, strontium carbonate, strontium
National Category
Other Materials Engineering Materials Engineering Other Engineering and Technologies not elsewhere specified
Research subject
Engineering Science with specialization in Nanotechnology and Functional Materials
Identifiers
urn:nbn:se:uu:diva-132377 (URN)978-91-554-7930-5 (ISBN)
Public defence
2010-12-10, Polhelmsalen, Ångströmslaboratoriet, Lägerhyddsvägen 1, Uppsala, 13:00 (Swedish)
Opponent
Supervisors
Note

Felaktigt tryckt som Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology 710

Available from: 2010-11-18 Created: 2010-10-19 Last updated: 2014-01-21Bibliographically approved
2. Biomaterials for Promoting Self-Healing of Bone Tissue
Open this publication in new window or tab >>Biomaterials for Promoting Self-Healing of Bone Tissue
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The present work addresses poor bone/implant integration and severe bone defects. In both conditions external stimuli is required for new bone to form. A multilayered functional implant coating, comprised of an inner layer of crystalline titanium dioxide (TiO2) and an outer layer of hydroxyapatite (HAP), loaded with bone morphogenetic protein-2 (BMP-2), was proposed as a tool for providing both improved initial bone formation and long-term osseointegration. The in vitro characterization of the implant coatings showed that TiO2 and HAP were more favorable for cell viability, cell morphology and initial cell differentiation, compared to native titanium oxide. Furthermore, significantly higher cell differentiation was observed on surfaces with BMP-2, indicating that a simple soaking process can be used for incorporating bioactive molecules. Moreover, the results suggest that there could be a direct interaction between BMP-2 and HAP, which prolongs the retention of the growth factor, improving its therapeutic effect.

For treating severe bone defects a strategy involving BMP-2 delivery from hyaluronan hydrogels was explored. The hydrogels were prepared from two reactive polymers – an aldehyde-modified hyaluronan and a hydrazide-modified poly(vinyl alcohol). Upon mixing, the two components formed a chemically crosslinked hydrogel. In this work the mixing of the hydrogel components was optimized by rheological measurements. Furthermore, an appropriate buffer was selected for in vitro experiments by studying the swelling of hydrogels in PBS and in cell culture medium. A detection method, based on radioactive labeling of BMP-2 with 125I was used to monitor growth factor release both in vitro and in vivo. The results showed a biphasic release profile of BMP-2, where approximately 16 %  and 3 % of the growth factor remained inside the hydrogel after 4 weeks in vitro and in vivo, respectively. The initial fast release phase corresponded to the early ectopic bone formation observed 8 d after injection of the hydrogel formulation in the thigh muscle of rats. The hydrogel formulation could be improved by incorporation of HAP powder into the hydrogel formulation. Furthermore, bone formation could be increased by pre-incubation of the premixed hydrogel components inside the syringe prior to injection. Crushed hydrogels were also observed to induce more bone formation compared to solid hydrogels, when implanted subcutaneously in rats. This was thought to be due to increased surface area of the hydrogel, which allowed for improved cell infiltration.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2011. 70 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 857
Keyword
Osseointegration, implant coating, hyaluronan hydrogel, bone morphogenetic protein-2, hydroxyapatite, bone, delivery system, injectable, mixing, radioactive labeling
National Category
Biomaterials Science Polymer Chemistry
Research subject
Chemistry with specialization in Polymer Chemistry
Identifiers
urn:nbn:se:uu:diva-158939 (URN)978-91-554-8168-1 (ISBN)
Public defence
2011-11-11, Häggsalen, Ångströmlaboratoriet, Lägerhyddsvägen 1, Uppsala, 13:00 (English)
Opponent
Supervisors
Available from: 2011-10-21 Created: 2011-09-19 Last updated: 2011-11-04Bibliographically approved

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Forsgren, JohanBrohede, UlrikaEngqvist, HåkanStrømme, Maria

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