liu.seSearch for publications in DiVA
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Bisphosphonate coating on titanium screws increases mechanical fixation in rat tibia after two weeks
Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Orthopaedic Centre, Department of Orthopaedics Linköping.
Linköping University, Department of Physics, Chemistry and Biology. Linköping University, The Institute of Technology.
Linköping University, Department of Physics, Chemistry and Biology, Applied Physics. Linköping University, The Institute of Technology.
2008 (English)In: Journal of Biomedical Materials Research. Part A, ISSN 1549-3296, Vol. 86A, no 1, 220-227 p.Article in journal (Refereed) Published
Abstract [en]

Recently published data indicate that immobilized N-bisphosphonate enhances the pullout force and energy uptake of implanted stainless steel screws at 2 weeks in rat tibia. This study compares titanium screws with and without a bisphosphonate coating in the same animal model. The screws were first coated with an 100-nm thick crosslinked fibrinogen film. Pamidronate was subsequently immobilized into this film via EDC/NHS-activated carboxyl groups within the fibrinogen matrix, and finally another N-bisphosphonate, ibandronate, was physically adsorbed. The release kinetics of immobilized 14C-alendronate was measured in buffer up to 724 h and showed a 60% release within 8 h. Mechanical tests demonstrated a 32% (p = 0.04) and 48% (p = 0.02) larger pullout force and energy until failure after 2 weeks of implantation, compared to uncoated titanium screws. A control study with physically adsorbed pamidronate showed no effect on mechanical fixation, probably due to a too small adsorbed amount. We conclude that the fixation of titanium implants in bone can be improved by fibrinogen matrix-bound bisphosphonates.

Place, publisher, year, edition, pages
Hoboken, NJ, United States: John Wiley & Sons, 2008. Vol. 86A, no 1, 220-227 p.
Keyword [en]
Bisphosphonate, pull-out, titanium, drug release, gamma sterilization, stainless steel, rat, fibrinogen, coating
National Category
Surgery
Identifiers
URN: urn:nbn:se:liu:diva-15307DOI: 10.1002/jbm.a.31583ISI: 000256459500021OAI: oai:DiVA.org:liu-15307DiVA: diva2:113870
Available from: 2008-10-30 Created: 2008-10-30 Last updated: 2014-01-13Bibliographically approved
In thesis
1. Surface bound bisphosphonate for implant fixation in bone
Open this publication in new window or tab >>Surface bound bisphosphonate for implant fixation in bone
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Alternative title[sv]
Läkemedel bundet till implantatytan förbättrar implantatets förankring i ben
Abstract [en]

During the surgical preparation of bone, prior to insertion of an implant, bone will be traumatized which leads to local resorption. Consequently, early implant fixation might be reduced. Impaired early fixation, as evidenced by radiostereometry, has been associated with increased risk of late loosening. Bisphosphonates are known to inhibit bone resorption by osteoclasts and have shown to increase implant fixation when administered systemically or locally directly at the bone prior to implant insertion.

A method to bind bisphosphonates directly to the implant was developed. Stainless steel screws were coated with crosslinked fibrinogen, serving as an anchor for bisphosphonate attachment. The screws were inserted in the tibial metaphysis in rats and implant fixation was analyzed with pullout measurements. Bisphosphonate coated screws turned out to have 28 % higher pullout force at 2 weeks compared to control screws with the fibrinogen coating only. The next experiment was designed to measure at what stage in the healing process the strongest bisphosphonate effect was gained. Bisphosphonate coated screws were expected to reduce the resorption of the traumatized bone. However, no decreased fixation was found in the control group. Instead, the fixation increased with time, and so did the effect of the bisphosphonates. At 8 weeks, the pullout force was twice as high for screws with bisphosphonate compared to control screws. By histology at 8 weeks, a bone envelope was found around bisphosphonate coated screws but absent around control screws. Thus, the anti catabolic action of the bisphosphonate resulted in an increased amount of bone surrounding the bisphosphonate screws.

Titanium is generally considered to be better fixated in bone compared to stainless steel. The coating technique was found to be applicable on titanium as well, again with improved fixation.

A majority of fractures occur in osteoporotic bone. Despite the relatively low amount of bisphosphonates at the screws, the bisphosphonate coating improved implant fixation at 2 weeks also in rats made osteoporotic by ovariectomy.

In conclusion, bisphosphonates bound to titanium or stainless steel screws coated with fibrinogen increased fixation in bone, in rats. These results suggest that the bisphosphonate and fibrinogen coating might improve the fixation of screw shaped implants and possibly also arthroplasties, in humans.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2008. 49 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1059
National Category
Surgery
Identifiers
urn:nbn:se:liu:diva-15310 (URN)978-91-7393-919-5 (ISBN)
Public defence
2008-05-21, Elsa Brännströms sal, Campus US, Hälsouniversitetet, Linköpings universitet, Linköping, 13:00 (English)
Opponent
Supervisors
Available from: 2008-10-30 Created: 2008-10-30 Last updated: 2012-01-19Bibliographically approved
2. Improved titanium and steel implants: Studies on bisphosphonate, strontium and surface treatments
Open this publication in new window or tab >>Improved titanium and steel implants: Studies on bisphosphonate, strontium and surface treatments
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Purpose: The general aim of this thesis was to increase the understanding of biomaterial surface modifications and local delivery of osteoporosis drugs for bone integration. We therefore (i) characterised and investigated model surface coatings for controlled drug delivery in a rat tibia screw model (ii) elucidated the effect of surface treatment for activation of complement system in vitro.

Materials and methods: Bisphosphonate was immobilised directly to implant surfaces by two methods. In the first method, bisphosphonate was bound via a crosslinked fibrinogen layer to titanium surfaces. In the second method, stainless steel screws were first dip coated in a TiO2 solgel, and thereafter incubated in simulated body fluid (SBF). The so prepared thin calcium phosphate layer on titania bound then bisphosphonate directly with high affinity. The drug release kinetics was determined in vitro by 14C marked alendronate that was quantified with scintillation techniques. The screws were inserted in the metaphysis of rat tibia and the mechanical fixation monitored by screw pullout measurements after 2 or 4 weeks of implantation. In order to compare two different osteoporosis drugs, bisphosphonate and strontium ranelate, stainless steel and PMMA screws were inserted in the tibial metaphysis of rat for 4 and 8 weeks. Bisphosphonate was then delivered subcutaneously and strontium ranelate orally during the whole implantation period. The mechanical fixation was analysed by pullout force measurements, and bone architecture studied by micro-computed tomography (μCT). The immune complement activation on sol-gel- and smooth titanium surfaces was analysed in human blood plasma before and after annealing of titanium at 100-500ºC or upon UVO-treatment for up to 96 hours.

Results: Bisphosphonate coated screws enhanced the screw pull out force after 2 weeks of implantation by more than 30% (fibrinogen coating) and by 93% after 4 weeks (sol-gel derived TiO2 coating). Systemically administered bisphosphonate enhanced the mechanical screw fixation after 4 weeks by more than 96% and after 8 weeks by more than 55% as compared to strontium ranelate treated animals (p = 0.00). Strontium ranelate treatment did not show significant improvement of screw pullout force after 4 and 8 weeks, compared to control. The immune complement surface deposition from blood plasma vanished irreversibly after Ti heat treatment at 250-300 ºC during 30 minutes or after UVO exposure for 24 hours or longer. Tentatively, changes in surface water/hydroxyl binding upon heat- and UVO treatments were observed by XPS and infrared spectroscopy.

Conclusions: The results show that fixation at short implantation time (weeks) of orthopaedic implant can be enhanced by immobilised bisphosphonate on stainless steel or titanium implants. Systemic delivery of strontium ranelate showed no significant effect on implant fixation in rat tibia, and we hypothesise therefore that strontium ranelate will not become a power tool to increase the early implant fixation, but may be beneficial at longer times. Heat annealing or UVO-treatment of titanium surfaces change the surface hydroxylation, leading to decreased immune complement deposition from blood plasma.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2011. 75 p.
Series
Linköping Studies in Science and Technology. Dissertations, ISSN 0345-7524 ; 1391
National Category
Natural Sciences
Identifiers
urn:nbn:se:liu:diva-71289 (URN)978-91-7393-085-7 (ISBN)
Public defence
2011-10-07, Planck, Fysikhuset, Campus Valla, Linköpings universitet, Linköping, 10:15 (Swedish)
Opponent
Supervisors
Available from: 2011-10-10 Created: 2011-10-10 Last updated: 2011-10-10Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textLink to Ph.D. Thesis

Authority records BETA

Wermelin, KarinAspenberg, PerLinderbäck Stenfors, PaulaTengvall, Pentti

Search in DiVA

By author/editor
Wermelin, KarinAspenberg, PerLinderbäck Stenfors, PaulaTengvall, Pentti
By organisation
Orthopaedics and Sports MedicineFaculty of Health SciencesDepartment of Orthopaedics LinköpingDepartment of Physics, Chemistry and BiologyThe Institute of TechnologyApplied Physics
In the same journal
Journal of Biomedical Materials Research. Part A
Surgery

Search outside of DiVA

GoogleGoogle Scholar

doi
urn-nbn

Altmetric score

doi
urn-nbn
Total: 254 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf