Co-precipitation of tobramycin into biomimetically coated orthopedic fixation pins employing submicron-thin seed layers of hydroxyapatite.

The migration, loosening and cut-out of implants and nosocomial infections are current problems associated with implant surgery. New innovative strategies to overcome these issues are emphasized in today's research. The current work presents a novel strategy involving co-precipitation of tobramycin with biomimetic hydroxyapatite (HA) formation to produce implant coatings that control local drug delivery to prevent early bacterial colonization of the implant. A submicron- 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 for a thin tobramycin- delivering HA coating on discs and orthopedic fixation pins. The morphology and thickness of the coating and the drug-release profile were evaluated via scanning electron microscopy and high performance liquid chromatography. The coatings delivered pharmaceutically relevant amounts of tobramycin over a period of 12 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 could form the foundation for development of combination device/antibiotic delivery vehicles tailored to meet well-defined clinical needs while combating infections and ensuring fast implant in-growth.

Biomechanical and antibacterial properties of Tobramycin loaded hydroxyapatite coated fixation pins.

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.

Drug loading and release of Tobramycin from hydroxyapatite coated fixation pins.

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.

Bone response to physical-vapour-deposited titanium dioxide coatings on titanium implants.

OBJECTIVES: The aim of this study was to investigate the correlation between coating thickness and the crystal structure of physical-vapour-deposited (PVD) titanium dioxide coatings, and to evaluate their in vivo biocompatibility. MATERIALS AND METHODS: The PVD TiO 2 coatings of different thickness were deposited on machined titanium grade 2 screw-shaped implants. Non-coated titanium implants were used as controls. Coating properties such as thickness, crystal structure, coating morphology and roughness were characterized. Forty-eight implants were placed randomly into both tibias of 16 rats. The animals were euthanized 7 and 28 days postsurgery and block biopsies were prepared for histology, histomorphometry and SEM analysis. RESULTS: The thicknesses of the PVDTiO 2 coatings were 120 and 1430 nm respectively. Histologically, new bone formed on all implant surfaces. The mean percentage of newly formed bone in contact with the implant (BIC) was significantly higher at early healing time (7 days) for the 120 nm thick PVD coating (39 ± 14%) than for both the 1430 nm thick PVD coating (22 ± 10%) (P = 0.043) and the machined surface (22 ± 9%) (P = 0.028). This difference was no longer evident after 28 days (P = 0.867). CONCLUSION: Bone formation and bone-to-implant contact are achieved to the same degree for TiO 2 surface modifications prepared by a PVD process as clinically used, machined titanium. Furthermore, a relatively thinner PVD coating promotes a higher degree of bone apposition shortly after implantation, thereby providing rationales for exploring the potential clinical use of these modifications.

Photocatalytic and antimicrobial properties of surgical implant coatings of titanium dioxide deposited though cathodic arc evaporation.

Nanostructured crystalline titanium dioxide coatings deposited by cathodic arc evaporated on titanium grade five medical implant substrates were demonstrated to exhibit UV-induced photocatalytic activity that can be utilized to provide bactericidal effects against Staphylococcus epidermidis. The photocatalytic activity of the coatings was confirmed via degradation of Rhodamine B under UV illumination. A 90 % reduction of viable bacteria was achieved in a clinically suitable time of only 2 min with a UV dose of 2.4 J delivered at 365 nm. These results are encouraging for the development of antimicrobial surfaces in orthopedics and dentistry in order to prevent or treat post-surgical infections. PURPOSE OF WORK: To assess the possibility of employing photocatalysis for elimination of S. epidermidis, known to cause medical device related infections, under short enough times to be clinically useful on an implant surface produced with a technique that is suitable for mass production.

Effect of deposition parameters on the photocatalytic activity and bioactivity of TiO2 thin films deposited by vacuum arc on Ti-6Al-4V substrates.

This article evaluates the influence of the main parameters in a cathodic arc deposition process on the microstructure of titanium dioxide thin coatings and correlates these to the photocatalytic activity (PCA) and in vitro bioactivity of the coatings. Bioactivity of all as deposited coatings was confirmed by the growth of uniform layers of hydroxyapatite (HA) after 7 days in phosphate buffered saline at 37°C. Comparison of the HA growth after 24 h indicated enhanced HA formation on coatings with small titanium dioxide grains of rutile and anatase phase. The results from the PCA studies showed that coatings containing a mixed microstructure of both anatase and rutile phases, with small grain sizes in the range of 26-30 nm and with a coating thickness of about 250 nm, exhibited enhanced activity as compared with other microstructures and higher coating thickness. The results of this study should be valuable for the development of new bioactive implant coatings with photocatalytically induced on-demand antibacterial properties.

Influence of microstructure and chemical composition of sputter deposited TiO2 thin films on in vitro bioactivity.

Functionalisation of biomedical implants via surface modifications for tailored tissue response is a growing field of research. Crystalline TiO(2) has been proven to be a bone bioactive, non-resorbable material. In contact with body fluids a hydroxyapaptite (HA) layer forms on its surface facilitating the bone contact. Thus, the path of improving biomedical implants via deposition of crystalline TiO(2) on the surface is interesting to follow. In this study we have evaluated the influence of microstructure and chemical composition of sputter deposited titanium oxide thin films on the in vitro bioactivity. We find that both substrate bias, topography and the flow ratio of the gases used during sputtering affect the HA layer formed on the films after immersion in simulated body fluid at 37°C. A random distribution of anatase and rutile crystals, formed at negative substrate bias and low Ar to O(2) gas flow ratios, are shown to favor the growth of flat HA crystal structures whereas higher flow ratios and positive substrate bias induced growth of more spherical HA structures. These findings should provide valuable information when optimizing the bioactivity of titanium oxide coatings as well as for tailoring process parameters for sputtered-based production of bioactive titanium oxide implant surfaces.