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- Lilja, Mirjam, 1981-, et al.
(författare)
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Drug loading and release of Tobramycin from Hydroxyapatite coated fixation pins
- 2013
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Ingår i: Journal of materials science. Materials in medicine. - : Springer Science and Business Media LLC. - 0957-4530 .- 1573-4838. ; 24:9, s. 2265-2274
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Tidskriftsartikel (refereegranskat)abstract
- This paper evaluates the loading and release properties of Tobramycin incorporated by adsorptive loading from a solution into plasma sprayed and biomimetically coated Hydroxyapatite (HA) fixation pins. The aim of this study is to contribute towards designing a functional implant surface offering local release of the antibiotic agent to prevent post-surgical infections. Cathodic arc deposition is used to coat stainless steel fixation pins with a bioactive, anatase phase dominated, TiO2 coating onto which a HA layer is grown biomimetically. The loading and release properties are evaluated by studying the subsequent release of Tobramycin using high performance liquid chromatography and correlated to the differences in HA coating microstructure and the physical conditions under loading. The results from these studies show that a dual loading strategy consisting of a solution temperature of 90 °C and a pressure of 6 bar during a loading time of 5 min release a sufficient amount of Tobramycin to guarantee the inhibition of Staphylococcus aureus up to 2 days for plasma sprayed HA coatings and for 8 days for biomimetic coatings. The present study emphasizes the advantages of the nanoporous structure of biomimetically deposited HA over the more dense structure of plasma sprayed HA coatings in terms of antibiotic incorporation and subsequent sustained release and provides a valuable outline for the design of implant surfaces aiming for a fast-loading and controlled, local drug administration.
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- Lilja, Mirjam, 1981-, et al.
(författare)
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Impact of Biomechanical Forces on Antibiotics Release Kinetics from Hydroxyapatite Coated Surgical Fixation Pins
- 2013
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Ingår i: Journal of Biomaterials and Nanobiotechnology. - : Scientific Research Publishing, Inc.. - 2158-7027 .- 2158-7043. ; 4:4, s. 343-350
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Tidskriftsartikel (refereegranskat)abstract
- This work investigates the impact of biomechanical wear and abrasion on the antibiotic release profiles of hydroxyapa-tite (HA) coated fixation pins during their insertion into synthetic bone. Stainless steel fixation pins are coated with crystalline TiO2 by cathodic arc evaporation forming the bioactive layer for biomimetic deposition of Tobramycin con-taining HA. Tobramycin is either introduced by co-precipitation during HA formation or by adsorption-loading after HA deposition. The samples containing antibiotics are inserted into bone mimicking polyethylene foam after which the drug release is monitored using high performance liquid chromatography. This analysis shows that HA coating wear and delamination significantly decrease the amount of drug released during initial burst, but only marginally influence the sustained release period. Spalled coating fragments are found to remain within the synthetic bone material structure. The presence of HA within this structure supports the assumption that the local release of Tobramycin is not only ex-pected to eliminate bacteria growth directly at the pin interface but as well at some distance from the implant. Further-more, no negative effect of gamma sterilization could be observed on the drug release profile. Overall, the observed results demonstrate the feasibility of a multifunctional implant coating that is simultaneously able to locally deliver clinically relevant doses of antibiotics and an HA coating capable of promoting osteoconduction. This is a potentially promising step toward orthopaedic devices that combine good fixation with the ability to treat and prevent post-surgical infections.
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- Sörensen, Jan Henrik, et al.
(författare)
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Biomechanical and Antibacterial Properties of Tobramycin Loaded Hydroxyapatite Coated Fixation Pins
- 2014
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Ingår i: Journal of Biomedical Materials Research. Part B - Applied biomaterials. - : Wiley. - 1552-4973 .- 1552-4981. ; 102:7, s. 1381-1392
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Tidskriftsartikel (refereegranskat)abstract
- The present study investigates the use of nanoporous, biomimetic hydroxyapatite (HA) coatings deposited on TiO2 coated fixation pins as functional implant surfaces for the local release of Tobramycin in order to prevent bacterial colonization. The impact of HA-coating thickness, coating morphology and biomechanical forces during insertion into synthetic bone on the drug loading and release properties are analyzed. The coatings are shown to exhibit bactericidal effects against Staphylococcus aureus in agar medium for a duration of 6 days after loading by adsorption with Tobramycin for only 5 min at elevated temperature and pressure. Furthermore, high performance liquid chromatography analysis shows a drug release in phosphate buffered saline for 8 days with antibiotic concentration remaining above the minimal inhibitory concentration for S. aureus during the entire release period. Biomechanical insertion tests into synthetic bone and conventional scratch testing demonstrate adhesive strength at the HA/TiO2 interface. Biocompatibility is verified by cell viability tests. Outgrowth endothelial cells, as well as primary osteoblasts, are viable and firmly attached to both HA and TiO2 surfaces. The results presented are encouraging and support the concept of functional HA coatings as local drug delivery vehicles for biomedical applications to treat as well as to prevent post-surgical infections.
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- Sörensen, Jan Henrik, et al.
(författare)
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Biomimetic Hydroxyapatite Coated Titanium Screws Demonstrate Rapid Implant Stabilization and Safe Removal In-Vivo
- 2015
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Ingår i: Journal of Biomaterials and Nanobiotechnology. - : Scientific Research Publishing, Inc.. - 2158-7027 .- 2158-7043. ; 6, s. 20-35
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Tidskriftsartikel (refereegranskat)abstract
- The early fixation of bone screws after surgical implantation still remains a challenge in the fieldof traumatology. Whilst hydroxyapatite (HA) coatings are known to enhance the fixation of implants;their removal at a later time-point may be problematic. An HA coating has been developedto demonstrate that both implant fixation and safe removal are feasible in the same design. Accordinglythe aim of this study was to compare the in-vivo performance of thin biomimetic HA coatedtitanium screws to uncoated counterparts used as control after bilateral implantation in the femoralcondyle of 36 New Zealand White Rabbits. The screws were analysed macroscopically, byhistology, micro-CT and biomechanically at both two and six weeks post-implantation. The HAcoated screws demonstrated excellent biocompatibility. At two weeks the HA coated screws demonstrateda significant increase in removal torque values as well as a strong trend towards higherpull-out forces. In addition histology confirmed a higher degree of osseointegration and directbone to implant contact. At six weeks no difference in pull-out force and removal torque could bedetected. SEM images confirmed the absence of any residual HA coating indicating a fast coatingdegradation in-vivo. The low level of removal torque after full osseointegration at 6 weeks supportsthe feasibility of safe and easy removal of the implant. The HA coating under study appearsto offer a unique characteristic of enhanced fixation with a minimal increase in removal torqueafter full osseointegration. This may be of value in clinical applications where it is necessary toassure both screw fixation and later removal.
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- Sörensen, Jan H, et al.
(författare)
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Co-precipitation of Tobramycin into Biomimetically Coated Orthopedic Fixation Pins Employing Submicron-Thin Seed Layers of Hydroxyapatite
- 2014
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Ingår i: Current Drug Delivery. - : Bentham Science Publishers Ltd.. - 1567-2018 .- 1875-5704. ; 11:4, s. 501-510
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Tidskriftsartikel (refereegranskat)abstract
- Implant migration, loosening and cut-out as well as nosocomial infections are current problems during surgery. New innovative strategies to overcome these issues are emphasized in today's research. The currentwork presents a novel strategy involving co-precipitation ofTobramycin with biomimetic hydroxyapatite (HA) formation to produce implant coatings that may ensure controlled local drug delivery to prevent early bacterial colonization of the implant. A sub-micron thin HA layer served as seed layer for the co-precipitation process and allowed for incorporation of Tobramycin in the coating from a stock solution of antibiotic concentrations as high as 20 mg/ml. Concentrations from 0.5 to 20 mg/ml Tobramycin and process temperatures of 37 °C and 60 °C were tested to assess the optimal parameters resulting in a thin Tobramycin delivering HA coating on discs and orthopedic fixation pins. The coating morphology and thickness as well as drugrelease profile were evaluated via scanning electron microscopy and high performanceliquid chromatography. The coatings were found to deliver pharmaceutically relevant amounts of Tobramycinover a period as of12 days. To the best of our knowledge, this is the longest release period ever observed for a fast-loaded biomimetic implant coating. The presented approach may form thefoundation for development of combination device/antibiotic delivery vehicles tailored to meet well-defined clinical needs combatting infections and ensuring fast implant in-growth.
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- Sörensen, Torben C, et al.
(författare)
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Bone substitute materials delivering zoledronic acid: Physicochemical characterization, drug load, and release properties.
- 2013
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Ingår i: Journal of biomaterials applications. - : SAGE Publications. - 1530-8022 .- 0885-3282. ; 27:6, s. 727-38
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Tidskriftsartikel (refereegranskat)abstract
- Calcium phosphate-like bone substitute materials have a long history of successful orthopedic applications such as bone void filling and augmentation. Based on the clinical indications, these materials may be loaded with active agents by adsorption offering a perspective for providing innovative drug-delivery systems. The highly effective bisphosphonate zoledronic acid (ZOL) demonstrated a strong affinity to biominerals and is known to significantly reduce osteoclastic activity. Support of early bone formation and reduction of bone resorption can be promoted after implantation of bioceramics releasing ZOL. The aim of this study was to develop an easy to handle approach to combine ZOL with bone substitutes by use of a dipping technique. The properties of three different materials were investigated by using a number of physicochemical methods such as light microscopy, scanning electron microscopy (SEM), dynamic vapor sorption (DVS), true density, and surface area measurement to evaluate the feasibility of being potential drug carriers. Besides physicochemical characterization, the bone substitutes were evaluated by their ZOL-loading capacity in a time- and concentration-dependent manner. Additionally, the materials were assessed as release systems in an in vitro study. Acontrolled ZOL load in a range of 0.04-1.86 µg/mg material and a release of 0.02-0.18 µg/mg within 30min is demonstrated. The findings support using the investigated bioceramics as carrier systems to release ZOL. Overall, the results create the base for further development of drug-delivery systems with controlled drug loading and prolonged release and need to be further analyzed in an in vivo study.
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