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In Vivo Evaluation of Functionalized Biomimetic Hydroxyapatite for Local Delivery of Active Agents
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.
Sandvik AB, Stockholm.
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Materials Chemistry, Polymer Chemistry.
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
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2011 (English)In: Journal of Biomaterials and Nanobiotechnology, ISSN 2158-7027, 2158-7043, Vol. 2, no 2, 149-154 p.Article 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.

Place, publisher, year, edition, pages
2011. Vol. 2, no 2, 149-154 p.
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: urn:nbn:se:uu:diva-156129DOI: 10.4236/jbnb.2011.22019OAI: oai:DiVA.org:uu-156129DiVA: diva2:430527
Funder
Swedish Research Council
Available from: 2011-07-11 Created: 2011-07-11 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)
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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

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Forsgren, JohanBrohede, UlrikaPiskounova, SonyaMihranyan, AlbertMaria, StrømmeEngqvist, Håkan

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