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Wermelin, Karin
Publications (9 of 9) Show all publications
Linderbäck, P., Agholme, F., Wermelin, K., Närhi, T., Tengvall, P. & Aspenberg, P. (2012). Weak effect of strontium on early implant fixation in rat tibia. Bone, 50(1), 350-356
Open this publication in new window or tab >>Weak effect of strontium on early implant fixation in rat tibia
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2012 (English)In: Bone, ISSN 8756-3282, E-ISSN 1873-2763, Vol. 50, no 1, p. 350-356Article 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
Keywords
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
Wermelin, K., Tengvall, P. & Aspenberg, P. (2008). A bisphosphonate coating improves the bony fixation of stainless steel screws in ovariectomized rats.
Open this publication in new window or tab >>A bisphosphonate coating improves the bony fixation of stainless steel screws in ovariectomized rats
2008 (English)Article in journal (Refereed) Submitted
Abstract [en]

Background: Bisphosphonate coatings improve the fixation of implants in bone. Stainless steels screws inserted in the rat tibia become encapsulated by new bone if they are coated with bisphosphonates in a crosslinked fibrinogen matrix. Thereby, the coating leads to a gradual increase in pull-out force. We now investigate if this bisphosphonate coating is capable to improve the mechanical fixation also in osteoporotic bone.

Methods: Stainless steel screws were coated with a thin crosslinked fibrinogen matrix. With EDC/NHS coupling technique, pamidronate was bound to carboxylic groups and ibandronate was adsorbed in the fibrinogen matrix. Uncoated stainless steel screws and bisphosphonatecoated screws were inserted bilaterally in the proximal tibia in 10 ovariectomized and 10 sham operated rats. At 2 weeks pull-out force and energy was measured.

Results: In the ovariectomized rats, pull-out force was 53 % higher for bisphosphonate coated screws compared to control screws. Energy was 44 % higher. The sham operated rats showed a higher variation, and no effect of the coating was found.

Conclusion: The coating was sufficient to improve fixation in ovariectomized rats

National Category
Surgery
Identifiers
urn:nbn:se:liu:diva-15309 (URN)
Available from: 2008-10-30 Created: 2008-10-30 Last updated: 2009-08-21Bibliographically approved
Aspenberg, P., Wermelin, K., Tengwall, P. & Fahlgren, A. (2008). Additive effects of PTH and bisphosphonates on the bone healing response to metaphyseal implants in rats. Acta Orthopaedica, 79(1), 111-115
Open this publication in new window or tab >>Additive effects of PTH and bisphosphonates on the bone healing response to metaphyseal implants in rats
2008 (English)In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 79, no 1, p. 111-115Article in journal (Refereed) Published
Abstract [en]

 BACKGROUND: When PTH is used to increase the amount of bone in osteoporotic patients, combination with bisphosphonates is known to attenuate the response. This might be explained by the reduced number of remodeling sites after bisphosphonate treatment, which reduces the number of cells able to respond to PTH. However, in a repair situation after trauma, a large number of osteoblasts reside in the wound site. If their activity is no longer coupled to osteoclasts, decreased resorption by bisphosphonates and stimulation of osteoblastic activity by PTH should both (independently) increase bone formation. Thus, we hypothesized that in contrast to the case in osteoporosis treatment, PTH and bisphosphonates have an additive effect in situations involving bone regeneration. MATERIAL AND METHODS: Stainless steel screws, either coated with biphosphonates or uncoated, were inserted in 46 rat tibias. This normally elicits a bone repair response, leading to a gradual increase in the strength of screw fixation. Half of the rats also received daily injections of teriparatide (PTH). Thus, there were 4 groups: control, bisphosphonate, PTH, and bisphosphonate plus PTH. Pull-out force and energy were measured after 2 weeks. RESULTS: The combined treatment had the strongest effect. It doubled the pull-out force and tripled the pull-out energy, compared to untreated controls. Also, bisphosphonate or PTH alone increased the pull-out force and energy, although less. No treatment cross-dependency was observed. INTERPRETATION: Because bisphosphonates mainly influence osteoclasts, and intermittent administration of PTH mainly influences osteoblasts, our findings indicate that to a large extent these cells work without coupling in this model. It appears that bisphosphonates are unlikely to attenuate the response to PTH during the formation of new bone.

Keywords
Animals Bone Density/drug effects Bone Density Conservation Agents/*pharmacology Bone Regeneration/drug effects Bone Remodeling/*drug effects Bone Screws Coated Materials, Biocompatible/pharmacology Diphosphonates/*pharmacology Fracture Healing/drug effec
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-43151 (URN)10.1080/17453670710014851 (DOI)72086 (Local ID)72086 (Archive number)72086 (OAI)
Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2017-12-13
Wermelin, K., Aspenberg, P., Linderbäck Stenfors, P. & Tengvall, P. (2008). Bisphosphonate coating on titanium screws increases mechanical fixation in rat tibia after two weeks. Journal of Biomedical Materials Research. Part A, 86A(1), 220-227
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, p. 220-227Article 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
Keywords
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
Wermelin, K., Suska, F., Tengvall, P., Thomsen, P. & Aspenberg, P. (2008). Stainless steel screws coated with bisphosphonates gave stronger fixation and more surrounding bone. Histomorphometry in rats. Bone, 42(2), 365-371
Open this publication in new window or tab >>Stainless steel screws coated with bisphosphonates gave stronger fixation and more surrounding bone. Histomorphometry in rats
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2008 (English)In: Bone, ISSN 8756-3282, E-ISSN 1873-2763, Vol. 42, no 2, p. 365-371Article in journal (Refereed) Published
Abstract [en]

Coating of stainless steel screws with bisphosphonate in a fibrinogen matrix leads to an enhancement of the pullout strength 2 weeks after insertion in rat tibiae. This effect then increases over time until at least 8 weeks. The pullout force reflects the mechanical properties of the bone within the threads, which acts as a screw nut. The aim of the present study was to find descriptive and morphometric histological correlates to the increased pullout strength. Because the bisphosphonates are applied via the implant surface, we also measured bone to implant contact and how far away from the surface any effects could be seen.

Stainless steel screws underwent one of three treatments: uncoated control, controls coated with a layer of cross-linked fibrinogen, or screws further modified with bisphosphonates covalently linked and physically adsorbed to the fibrinogen layer. At 1 (n = 33) and 8 (n = 27) weeks, bone to implant contact and bone area density in the threads were measured, as well as bone area density at 250 and 500 μm from the outer edge of the threads. Additionally, removal torque for each screw treatment was measured at 2 weeks (n = 28).

At 8 weeks, the part of the bisphosphonate screw that was located in the marrow cavity had become surrounded with bone, whereas there was almost no bone surrounding the controls. The bone area density in the threads along the entire bisphosphonate screw was increased by 40% compared with uncoated controls, and at 250 μm distance it was more than doubled. At 1 week, coated screws had less implant–bone contact, but at 8 weeks there was no difference between uncoated and bisphosphonate-coated screws. The bisphosphonate screws had 50% increased removal torque at 2 weeks compared to uncoated screws. Howship's lacunae and osteoclasts were found near the screws with bisphosphonates at 8 weeks, suggesting that some bone remodeling took place near the implant, in spite of the presence of bisphosphonates.

Place, publisher, year, edition, pages
Elsevier/ScienceDirect, 2008
Keywords
Histomorphometry; Stainless steel; Torque removal; Bisphosphonate; Implant fixation
National Category
Surgery
Identifiers
urn:nbn:se:liu:diva-15308 (URN)10.1016/j.bone.2007.10.013 (DOI)
Available from: 2008-10-30 Created: 2008-10-30 Last updated: 2017-12-14Bibliographically approved
Wermelin, K. (2008). Surface bound bisphosphonate for implant fixation in bone. (Doctoral dissertation). Linköping: Linköping University Electronic Press
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. p. 49
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
Wermelin, K., Tengvall, P. & Aspenberg, P. (2007). Surface-bound bisphosphonates enhance screw fixation in rats—increasing effect up to 8 weeks after insertion. Acta Orthopaedica, 78(3), 385-392
Open this publication in new window or tab >>Surface-bound bisphosphonates enhance screw fixation in rats—increasing effect up to 8 weeks after insertion
2007 (English)In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 78, no 3, p. 385-392Article in journal (Refereed) Published
Abstract [en]

Background: A bisphosphonate coating improves screw fixation 2 weeks after implantation in cancellous bone. This study on rats examined further development of fixation over time for screws inserted in cancellous and cortical bone.

Methods: SS screws were coated with a multiple layer of fibrinogen. Half of the screws were coated further with bisphosphonates, which were linked to the fibrinogen. The screws were inserted in cancellous and cortical bone in rats. The rats were killed after 5 h, 4 days, 1, 2, 4, 8, and 24 weeks, and fixation was evaluated by pullout test.

Results: There was a gradual increase in pull-out force over time in both cancellous and cortical bone. The bisphosphonate coating improved fixation. Moreover, the difference between the bisphosphonate and control groups increased with time. The pull-out force was almost twice that of the controls for screws inserted in cancellous bone at 8 weeks. Energy uptake was increased more than 3-fold.

Discussion: The energy uptake and pull-out force of a screw depends on the bone engaged with the threads. Thus, the presence of bisphosphonates increased the amount or quality of this bone by affecting the resorp-tion/formation in a positive way. The increased effect of the bisphosphonates with time thus suggests that bisphosphonate is retained within the remodeling bone, with a positive effect on its gradual adaptation to the implant.

Place, publisher, year, edition, pages
Talyor & Francis, 2007
National Category
Surgery
Identifiers
urn:nbn:se:liu:diva-15306 (URN)10.1080/17453670710013979 (DOI)
Available from: 2008-10-30 Created: 2008-10-30 Last updated: 2017-12-14Bibliographically approved
Wermelin, K., Tengvall, P. & Aspenberg, P. (2006). Surface Bound Bisphosphonate Enhances Screw Fixation up to 8 Weeks after Insertion. In: 52nd Annual Meeting of Orthopaedic Research Society,2006.
Open this publication in new window or tab >>Surface Bound Bisphosphonate Enhances Screw Fixation up to 8 Weeks after Insertion
2006 (English)In: 52nd Annual Meeting of Orthopaedic Research Society,2006, 2006Conference paper, Published paper (Other academic)
Abstract [en]

  

National Category
Natural Sciences
Identifiers
urn:nbn:se:liu:diva-39529 (URN)49425 (Local ID)49425 (Archive number)49425 (OAI)
Available from: 2009-10-10 Created: 2009-10-10
Petoral, R. J., Wermelin, K., Dahlstedt, E., Hellberg, J. & Uvdal, K. (2005). Adsorption of n-butyl-substituted tetrathiafulvalene dodecanethiol on gold. Journal of Colloid and Interface Science, 287(2), 388-393
Open this publication in new window or tab >>Adsorption of n-butyl-substituted tetrathiafulvalene dodecanethiol on gold
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2005 (English)In: Journal of Colloid and Interface Science, ISSN 0021-9797, E-ISSN 1095-7103, Vol. 287, no 2, p. 388-393Article in journal (Refereed) Published
Abstract [en]

Tetrathiafulvalene (TTF) derivative substituted with two butyl- and two dodecylthiol chains is adsorbed on polycrystalline gold. The TTF-derived thiol adsorbates were characterized by ellipsometry, contact angle goniometry, infrared and X-ray photoelectron spectroscopy and cyclic voltammetry. The molecule is strongly anchored on the gold surface through the sulfur terminating the alkylthiol chains. On the average, the TTF moiety is oriented extended away from the gold surface. The topmost layer of the film containing the dibutyl chains is disordered with gauche defects. The molecule was organized with majority of the alkylthiol chains bound to the gold surface. There are indications of pinholes in the monolayer due to steric hindrance of the bulky TTF rings. The molecular systems consisting of an electroactive π-system such as TTF, are promising for thin-film field effect transistor application. © 2005 Elsevier Inc. All rights reserved.

National Category
Natural Sciences
Identifiers
urn:nbn:se:liu:diva-44576 (URN)10.1016/j.jcis.2005.02.046 (DOI)77120 (Local ID)77120 (Archive number)77120 (OAI)
Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2017-12-13
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