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Improved titanium and steel implants: Studies on bisphosphonate, strontium and surface treatments
Linköping University, Department of Physics, Chemistry and Biology. Linköping University, The Institute of Technology.
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: urn:nbn:se:liu:diva-71289ISBN: 978-91-7393-085-7 (print)OAI: oai:DiVA.org:liu-71289DiVA: diva2:447026
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
List of papers
1. Bisphosphonate coating on titanium screws increases mechanical fixation in rat tibia after two weeks
Open this publication in new window or tab >>Bisphosphonate coating on titanium screws increases mechanical fixation in rat tibia after two weeks
2008 (English)In: Journal of Biomedical Materials Research. Part A, ISSN 1549-3296, E-ISSN 1552-4965, 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
Keyword
Bisphosphonate, pull-out, titanium, drug release, gamma sterilization, stainless steel, rat, fibrinogen, coating
National Category
Surgery
Identifiers
urn:nbn:se:liu:diva-15307 (URN)10.1002/jbm.a.31583 (DOI)000256459500021 ()
Available from: 2008-10-30 Created: 2008-10-30 Last updated: 2017-12-14Bibliographically approved
2. Sol-gel derived titania coating with immobilized bisphosphonate enhances screw fixation in rat tibia
Open this publication in new window or tab >>Sol-gel derived titania coating with immobilized bisphosphonate enhances screw fixation in rat tibia
2010 (English)In: JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A, ISSN 1549-3296, Vol. 94A, no 2, 389-395 p.Article in journal (Refereed) Published
Abstract [en]

A variety of surface modifications have been tested for the enhancement of screw fixation in bone, and locally delivered anti-osteoporosis drugs such as bisphosphonates (BP) are then of interest. In this in vivo study, the impact of surface immobilized BP was compared with systemic BP delivery and screws with no BP. After due in vitro characterization, differently treated stainless steel (SS) screws were divided into four groups with 10 rats each. Three of the groups received screws coated with sol gel derived TiO2 and calcium phosphate (SS+TiO2+CaP). One of these had no further treatment, one had alendronate (BP) adsorbed to calcium phosphate mineral, and one received systemic BP treatment. The fourth group received uncoated SS screws and no BP (control). The screw pullout force was measured after 4 weeks of implantation in rat tibiae. The immobilized amount and release rate of alendronate could be controlled by different immersion times. The SS+TiO2+CaP coating did not increase the pullout force compared to SS alone. Surface delivered alendronate enhanced the pullout force by 93% [p = 0.000; 95% Confidence Interval (CI): 67-118%] compared to SS, and by 39% (p = 0.044; 95% CI: 7-71%) compared to systemic alendronate delivery. Both surface immobilized and systemically delivered alendronate improved implant fixation. Also, locally delivered, that is, surface immobilized alendronate showed a better fixation than systemically delivered. Using sot gel derived TiO2 as a platform, it is possible to administer controllable amounts of a variety of BPs.

Place, publisher, year, edition, pages
John Wiley and Sons, Ltd, 2010
Keyword
screw; bone; bisphosphonates; sol-gel; rat
National Category
Engineering and Technology
Identifiers
urn:nbn:se:liu:diva-58262 (URN)10.1002/jbm.a.32708 (DOI)000279482600006 ()
Available from: 2010-08-10 Created: 2010-08-09 Last updated: 2011-10-10
3. The effect of heat- or ultra violet ozone-treatment of titanium on complement deposition from human blood plasma
Open this publication in new window or tab >>The effect of heat- or ultra violet ozone-treatment of titanium on complement deposition from human blood plasma
Show others...
2010 (English)In: BIOMATERIALS, ISSN 0142-9612, Vol. 31, no 18, 4795-4801 p.Article in journal (Refereed) Published
Abstract [en]

Titanium (Ti) is a well known metallic biomaterial extensively used in dental, orthopaedic-, and occasionally also in blood contacting applications. It integrates well to bone and soft tissues, and is shown upon blood plasma contact to activate the intrinsic pathway of coagulation and bind complement factor 3b. The material properties depend largely on those of the nm-thick dense layer of TiO2 that becomes rapidly formed upon contact with air and water. The spontaneously formed amorphous Ti-oxide has a pzc similar to 5-6 and its water solubility is at the order of 1-2 micromolar. It is often subjected to chemical- and heat treatments in order to increase the anatase- and ruble crystallinity, to modify the surface topography and to decrease the water solubility. In this work, we prepared sol gel derived titanium and smooth PVD titanium surfaces, and analysed their oxide and protein deposition properties in human blood plasma before and after annealing at 100-500 degrees C or upon UVO-treatment for up to 96 hours. The blood plasma results show that complement deposition vanished irreversibly after heat treatment at 250-300 degrees C for 30 minutes or after UVO exposure for 24 hours or longer. XPS and infrared spectroscopy indicated change of surface water/hydroxyl binding upon the heat- and UVO treatments, and increased Ti oxidation. XRD analysis confirmed an increased crystallinity and both control (untreated) and annealed smooth titanium displayed low XRD-signals indicating some nanocrystallinity, with predominantly anatase phase. The current results show that the behaviour of titanium dioxide in blood contact can be controlled through relatively simple means, such as mild heating and illumination in UV-light, which both likely irreversibly change the stoichiometry and structure of the outmost layers of titanium dioxide and its OH/H2O binding characteristics.

Place, publisher, year, edition, pages
Elsevier Science B.V., Amsterdam., 2010
Keyword
Titanium, Titanium oxide, Sol-gel, Blood plasma, Protein adsorption, Complement
National Category
Engineering and Technology
Identifiers
urn:nbn:se:liu:diva-56807 (URN)10.1016/j.biomaterials.2010.02.060 (DOI)000277783100002 ()
Available from: 2010-06-04 Created: 2010-06-04 Last updated: 2011-10-10
4. Weak effect of strontium on early implant fixation in rat tibia
Open this publication in new window or tab >>Weak effect of strontium on early implant fixation in rat tibia
Show others...
2012 (English)In: Bone, ISSN 8756-3282, E-ISSN 1873-2763, Vol. 50, no 1, 350-356 p.Article in journal (Refereed) Published
Abstract [en]

Strontium ranelate increases bone mass and is used in the treatment of osteoporosis. Its effects in metaphyseal bone repair are largely unknown. We inserted a stainless steel and a PMMA screw into each tibia of male Sprague-Dawley rats. The animals were fed with ordinary feed (n =40) or with addition of strontium ranelate (800mg/kg/day; n = 20). As a positive control, half of the animals on control feed received alendronate subcutaneously. The pullout force of the stainless steel screws was measured after 4 and 8 weeks, and μCT was used to assess bone formation around the PMMA screws. No significant effects of strontium treatment on pullout force were observed, but animals treated with bisphosphonate showed a doubled pullout force. Strontium improved the microarchitecture of the cancellous bone below the primary spongiosa at the growth plate, but no significant effects were found around the implants. Strontium is known to improve bone density, but it appears that this effect is weak in conjunction with metaphyseal bone repair and early implant fixation.

Place, publisher, year, edition, pages
Elsevier, 2012
Keyword
Bisphosphonate; bone; implant; rat; screw; Strontium ranelate
National Category
Natural Sciences
Identifiers
urn:nbn:se:liu:diva-71288 (URN)10.1016/j.bone.2011.10.034 (DOI)000299064200045 ()
Note
funding agencies|Swedish Research Council| VR-2009-6725 |local strategic research project Materials in Medicine||County Council of Ostergotland||Linkopings Universitet, Sweden||Available from: 2011-10-10 Created: 2011-10-10 Last updated: 2017-12-08Bibliographically approved

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