| 1. |
- Kettenberger, Ulrike, et al.
(författare)
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Does locally delivered Zoledronate influence pen-implant bone formation? : Spatio-temporal monitoring of bone remodeling in vivo
- 2014
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Ingår i: Biomaterials. - : Elsevier BV. - 0142-9612 .- 1878-5905. ; 35:37, s. 9995-10006
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Tidskriftsartikel (refereegranskat)abstract
- Bisphosphonates are known for their strong inhibitory effect on bone resorption. Their influence on bone formation however is less clear. In this study we investigated the spatio-temporal effect of locally delivered Zoledronate on pen-implant bone formation and resorption in an ovariectomized rat femoral model. A cross-linked hyaluronic acid hydrogel was loaded with the drug and applied bilaterally in predrilled holes before inserting polymer screws. Static and dynamic bone parameters were analyzed based on in vivo microCT scans performed first weekly and then biweekly. The results showed that the locally released Zoledronate boosted bone formation rate up to 100% during the first 17 days after implantation and reduced the bone resorption rate up to 1000% later on. This shift in bone remodeling resulted in an increase in bone volume fraction (BV/TV) by 300% close to the screw and 100% further away. The double effect on bone formation and resorption indicates a great potential of Zoledronateloaded hydrogel for enhancement of pen-implant bone volume which is directly linked to improved implant fixation.
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| 2. |
- Kettenberger, Ulrike, et al.
(författare)
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In vitro and in vivo investigation of bisphosphonate-loaded hydroxyapatite particles for peri-implant bone augmentation
- 2017
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Ingår i: Journal of Tissue Engineering and Regenerative Medicine. - : Hindawi Limited. - 1932-6254 .- 1932-7005. ; 11:7, s. 1974-1985
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Tidskriftsartikel (refereegranskat)abstract
- Locally applied bisphosphonates, such as zoledronate, have been shown in several studies to inhibit peri-implant bone resorption and recently to enhance peri-implant bone formation. Studies have also demonstrated positive effects of hydroxyapatite (HA) particles on peri-implant bone regeneration and an enhancement of the anti-resorptive effect of bisphosphonates in the presence of calcium. In the present study, both hydroxyapatite nanoparticles (nHA) and zoledronate were combined to achieve a strong reinforcing effect on peri-implant bone. The nHA-zoledronate combination was first investigated in vitro with a pre-osteoclastic cell assay (RAW 264.7) and then in vivo in a rat model of postmenopausal osteoporosis. The in vitro study confirmed that the inhibitory effect of zoledronate on murine osteoclast precursor cells was enhanced by loading the drug on nHA. For the in vivo investigation, either zoledronate-loaded or pure nHA were integrated in hyaluronic acid hydrogel. The gels were injected in screw holes that had been predrilled in rat femoral condyles before the insertion of miniature screws. Micro-CT-based dynamic histomorphometry and histology revealed an unexpected rapid mineralization of the hydrogel in vivo through formation of granules, which served as scaffold for new bone formation. The delivery of zoledronate-loaded nHA further inhibited a degradation of the mineralized hydrogel as well as a resorption of the peri-implant bone as effectively as unbound zoledronate. Hyaluronic acid with zoledronate-loaded nHA, thanks to its dual effect on inducing a rapid mineralization and preventing resorption, is a promising versatile material for bone repair and augmentation.
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| 3. |
- Munoz, Jorge Solana, et al.
(författare)
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Non-setting, injectable biomaterials containing particulate hydroxyapatite can increase primary stability of bone screws in cancellous bone
- 2018
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Ingår i: Clinical Biomechanics. - : Elsevier BV. - 0268-0033 .- 1879-1271. ; 59, s. 174-180
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Tidskriftsartikel (refereegranskat)abstract
- Background: Fracture fixation in weak bone is still a clinical challenge. Screw augmentation was shown to successfully increase their primary stability. The currently used calcium phosphate or polymeric bone cements, however, present important drawbacks such as induced toxicity and/or impaired bone neo-formation. A new approach to enhance bone screw primary stability without affecting bone formation is the use of non-setting, calcitim phosphate loaded soft materials as the augmentation material. Methods: Two types of biomaterials (non-crosslinked hyaluronic acid as viscous fluid and agar as hydrogel) were loaded with 40 wt/vol% of hydroxyapatite particles and characterized. The screw augmentation effect of all materials was evaluated through pull-out tests in bovine cancellous bone and compared to the non-augmented situation (control). The bone mineral density of each test sample was measured with CT scans and was used to normalize the pull-out strength. Findings: Both materials loaded with hydroxyapatite increased the normalized pull-out strength of the screws compared to control samples and particle-free materials. This counter-intuitive augmentation effect increased with decreasing bone mineral density and was independent from the type of the soft materials used. Interpretation: We were able to demonstrate that non-setting, injectable biomaterials loaded with ceramic particles can significantly enhance the primary stability of bone screws. This material combination opens the unique possibility to achieve a screw augmentation effect without impairing or even potentially favoring the bone formation in proximity to the screw. This effect would be particularly advantageous for the treatment of osteoporotic bone fractures requiring a stabilization with bone screws.
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