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Impact of Biomechanical Forces on Antibiotics Release Kinetics from Hydroxyapatite Coated Surgical Fixation Pins

Journal of Biomaterials and Nanobiotechnology 2013年第4期4卷 343-350页

作者： Mirjam Lilja Jan H.Sorensen Torben C.Sorensen Maria Astrand philip procter Hartwig Steckel Maria Stromme Division for Nanotechnology and Functional Materials Department of Engineering SciencesThe Angstrom LaboratoryUppsala UniversityUppsalaSweden Sandvik Coromant AB StockholmSweden Department of Pharmaceutics and Biopharmaceutics Christian Albrecht University KielKielGermany Stryker Trauma GmbH SchonkirchenGermany Stryker Trauma AG SelzachSwitzerland School of Engineering and Design Brunel UniversityUxbridgeUK

This work investigates the impact of biomechanical wear and abrasion on the antibiotic release profiles of hydroxyapatite (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 containing 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 expected to eliminate bacteria growth directly at the pin interface but as well at some distance from the implant. Furthermore, 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.

关键词： Hydroxyapatite Fixation Pin Tobramycin Coating Wear Drug Release Gamma Sterilization

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Biomimetic Hydroxyapatite Coated Titanium Screws Demonstrate Rapid Implant Stabilization and Safe Removal In-Vivo

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Journal of Biomaterials and Nanobiotechnology 2015年第1期6卷 20-35页

作者： Jan Henrik Sorensen Lutz Durselen Ken Welch Torben Christian Sorensen philip procter Hakan Engqvist Maria Stromme Anita Ignatius Hartwig Steckel Department of Pharmaceutics and Biopharmaceutics Christian-Albrechts UniversityKielGermany Institute of Orthopaedic Research and Biomechanics Centre of Musculoskeletal ResearchUlmGermany Division for Nanotechnology and Functional Materials The Angstrom LaboratoryUppsala UniversityUppsalaSweden Stryker Trauma GmbH SchonkirchenGermany Stryker Trauma AG SelzachSwitzerland Division for Applied Materials Sciences The Angstrom LaboratoryUppsala UniversityUppsalaSweden

The early fixation of bone screws after surgical implantation still remains a challenge in the field of 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 developed to demonstrate that both implant fixation and safe removal are feasible in the same design. Accordingly the aim of this study was to compare the In-Vivo performance of thin biomimetic HA coated titanium screws to uncoated counterparts used as control after bilateral implantation in the femoral condyle of 36 New Zealand White Rabbits. The screws were analysed macroscopically, by histology, micro-CT and biomechanically at both two and six weeks post-implantation. The HA coated screws demonstrated excellent biocompatibility. At two weeks the HA coated screws demonstrated a significant increase in removal torque values as well as a strong trend towards higher pull-out forces. In addition histology confirmed a higher degree of osseointegration and direct bone to implant contact. At six weeks no difference in pull-out force and removal torque could be detected. SEM images confirmed the absence of any residual HA coating indicating a fast coating degradation In-Vivo. The low level of removal torque after full osseointegration at 6 weeks supports the feasibility of safe and easy removal of the implant. The HA coating under study appears to offer a unique characteristic of enhanced fixation with a minimal increase in removal torque after full osseointegration. This may be of value in clinical applications where it is necessary to assure both screw fixation and later removal.

关键词： Biomimetic Hydroxyapatite In-Vivo Screw Implant Removal Pull-Out Force Removal Torque

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Histamine_2-receptor antagonists: Rapid development of tachyphylaxis with repeat dosing

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World Journal of Gastrointestinal Pharmacology and Therapeutics 2014年第2期5卷 57-62页

作者： Johnson W McRorie James A Kirby philip B Miner Quantitative Sciences Procter and GambleMasonOH 45040United States Corporate Pharmacy The Kroger CompanyCincinnatiOH 45246United States Oklahoma Foundation for Digestive Research Oklahoma CityOK 73104United StatesPresident

Histamine_2-receptor antagonists(H_2RAs) are availableover-the-counter (OTC) for the treatment and prevention of heartburn, but more than occasional, singledose use can lead to rapid development of tachyphylaxis. The aim of this review is to assess the publishedevidence regarding the development of tachyphylaxiswith repeat usage of H_2RAs. PubMed and SCOPUS were searched across all years to identify clinical studies thatexamined the development of tachyphylaxis with repeated dosing of H_2RAs. Although a single (first) doseof an H_2RA can be effective for controlling gastric acidand preventing or relieving food-related heartburn, numerous studies confirm that tachyphylaxis, also knownas tolerance, is consistently detected at the first timepoint assessed after the first dose, including the second day and/or second dose. Even if symptom relief isachieved with an H_2RA, it may be due to desensitizationof the esophagus to acid exposure, potentially providingsymptom relief without significantly decreasing esophageal acid exposure. When recommending OTC drugsfor treatment of frequent heartburn, clinicians shouldbe aware of the potential for rapid development oftachyphylaxis in patients who use H_2RAs for 2 or more consecutive days. Even if symptom relief is achieved, it may be due to desensitization of the esophagus to acid by the H_2RA, potentially providing symptom relief without significantly decreasing esophageal acid exposure. Other strategies, such as an OTC proton pump inhibitor, may be needed to optimize management of frequent heartburn.

关键词： Histamine2-receptor antagonist Tachyphylaxis Tolerance Gastric pH

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