In vivo testing of a bioabsorbable magnesium alloy serving as total ossicular replacement prostheses

Magnesium alloys have been investigated in different fields of medicine and represent a promising biomaterial for implants due to characteristics like bioabsorbability and osteoinduction. The objective of this study was to evaluate the usability of magnesium as implant material in middle ear surgery. Magnesium implants were placed into the right middle ear of eighteen New Zealand White rabbits. Nine animals were euthanized after four weeks and nine animals after three month. The petrous bones were removed and embedded in epoxy resin. The specimens were then polished, stained and evaluated with the aid of a light microscope. The histological examination revealed a good biocompatibility. After four weeks, a beginning corrosion of the implant's surface and low amount of trabecular bone formation in the area of the stapes base plate was observed. A considerable degradation of implants and obvious bone formation was found three month after implantation. The magnesium alloy used in the present study partly corroded too fast, so that a complete bone reconstruction could not be established in time. The increased osteoinduction on the stapes base plate resulted in a tight bone-implant bonding. Thus, a promising application of magnesium could be a coating of biomaterials in order to improve the bony integration of implants. © The Author(s) 2012 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav

Mesoporous silica films as a novel biomaterial: Applications in the middle ear

In this tutorial review we present the process of the development of functional implants using mesoporous silica. The different steps from chemical synthesis and physicochemical characterization followed by in vitro testing in cell culture assays to clinically relevant in vivo animal studies are examined. Since the end of the 1990s, mesoporous silicas have been considered as biomaterials. Numerous investigations have demonstrated their non-toxic and biocompatible properties. These qualities in combination with the unique properties of high surface area and pore volume, uniform and tunable pore sizes and chemical modifiability are the reasons for the great scientific interest in this field. Here we show that besides bulk materials or mesoporous silica nanoparticles, mesoporous silica films are highly promising as coatings on medical prostheses or implants. We report on the development of functionalized mesoporous silica materials specifically for middle ear applications. Middle ear prostheses are used to restore the sound transmission through this air-filled cavity when the small bones of the middle air (the ossicular chain) have been destroyed by disease or by accidents. In addition to optimal restoration of sound transmission, this technique bears several challenges, e.g. an ongoing bacterial infection or the displacement of the prosthesis due to insufficient fixation. To improve the healing process, a mesoporous silica coating was established on ceramic middle ear prostheses, which then served as a base for further functionalizations. For example, the bone growth factor BMP2 was locally attached to the coating in order to improve the fixation of the prosthesis by forming a bony connection to the remainder of the ear bones. Further, an implant-based local drug delivery system for the antibiotic ciprofloxacin was developed with the aim of fighting bacterial infections. Further possibilities using mesoporous silica nanoparticles as part of a composite on an implant are briefly discussed. © The Royal Society of Chemistry 2013

Nanoporous Silica Films as Novel Biomaterial: Applications in the Middle Ear

We have introduced nanoporous silica as a novel biomaterial. Nanoporous silica is non-toxic and biocompatible. It provides a high surface area and pore volume, uniform and tunable pore sizes and the possibility for chemical modification. We have shown that nanoporous silica coatings on middle ear prostheses provide a suitable basis for installing various functionalizations which can improve the healing after the insertion of the implant.DF

Different cell populations are inducible by BMP-2 covalently covered Bioverit® II implants in rabbit subcutis and middle ear

To optimize the function of implants the formation of surrounding connective tissue should be adapted in dependence to the mechanical conditions. Therefore, with nanostructured silica coated Bioverit® II implants were only partly reacted with recombinant BMP-2. The histology was compared 28, 84 and 301 days after implantation in the rabbit middle ear and subcutis, respectively. The whole tissue blocks were embedded in Epon, sequentially grinded, stained with Toluidine Blue O and Eosin G. The granulation tissue covering the implants varies related to cell types, cell amounts, extracellular matrix and vessels. Whereas the high cell density and the angiogenesis predominated in the subcutis, the formation of new bone could only be recognized in the scar around the implants in the middle ear.SFB/599/project D1

Nanoporous silica coatings on implant surfaces: characterization, stability, biocompatibility and drug release properties

Nanoporous silica coatings for drug release purposes were prepared on medical implants. As substrate, we chose Bioverit® II, which is a commercial available glass-mica ceramic implant material. The coating was prepared by a dip-coating technique in which long-chain organic molecules act as placeholders for the pores. Characterization of the coatings by scanning transmission electron microscopy and X-ray diffraction showed a disordered nanoporous system with a layer thickness of 30–150 nm. The nanoporous structure was stable for about 12 h in a typical cell culture medium and rearranged to a packing of silica nanoparticles. The coating allowed cell attachment and showed excellent biocompatibility in cell culture tests independently of the particular cell type examined. In vivo, implant-tissue interactions were examined in the middle ear in a novel mouse model. Whole genome expression profiling showed no persisting inflammatory response in the presence of the implants. Release profiles of the antibiotic ciprofloxacin demonstrated that the coating is suitable for a local drug delivery. The drug loading capacity could be drastically increased after sulfonic acid modification of the Bioverit® II surface

Mesoporous silica coatings for controlled release of the antibiotic ciprofloxacin from implants

To generate bioactive coatings for medical implants, a novel procedure has been developed using a coating of mesoporous silica for controlled drug delivery. Plain glass slides were used as substrates. The mesoporous coatings were then loaded with the antibacterial drug ciprofloxacin. The drug release kinetics were investigated in a physiological buffered solution. The drug loading capacity of the unmodified mesoporous coatings was low but could be increased nearly ten-fold (to about 2 g cm-2 of the macroscopic surface) by functionalizing the mesoporous surface with sulfonic acid groups. To achieve a controlled drug release over an extended time period, further coatings were added. Covering the surface of the drug loaded mesoporous silica layer by dip-coating with bis(trimethoxysilyl)hexane resulted in an organosiloxane layer which retarded the release for up to 30 days. By an additional evaporation coating with dioctyltetramethyldisilazane, the release of ciprofloxacin was prolonged for up to 60 days. The biocompatibility of the different coatings was tested in cell culture assays. The presence of the additional silane-derived hydrophobic coatings somewhat reduced the biocompatibility. The antibacterial efficacy of the materials was demonstrated by using clinically relevant biofilm-forming pathogenic bacteria. A test where the sequential release of ciprofloxacin (in 2 days intervals) and the bacterial viability were tested in parallel showed good concordance in the results. The material where a sulfonate-functionalized mesoporous silica layer is loaded with ciprofloxacin and then coated by an organosiloxane layer derived from bis(trimethoxysilyl)hexane showed the best results with regard to antibacterial efficacy and will further be tested in animal experiments

Evaluation of Madurahydroxylactone as a Slow Release Antibacterial Implant Coating

Madurahydroxylactone (MHL), a secondary metabolite with antibacterial activity was evaluated for its suitability to generate controlled drug release coatings on medical implant materials. A smooth and firmly attached layer could be produced from a precursor solution on various metallic implant materials. In physiological salt solutions these coatings dissolved within a time period up to one week. A combination of MHL with a broad spectrum fluoroquinolone antibiotic was used to create a coating that was active against all bacterial strains tested. The time period during which the coating remained active against Pseudomonas aeruginosa was investigated. The results indicated a delayed drug release from single layer coatings in the course of seven days. MHL was biocompatible in cell culture assays and could after a delay even serve as a cell adhesion substrate for human or murine cells. The findings indicate a potential for MHL for the generation of delayed release antimicrobial implant coatings

Dose optimisation in paediatric radiography - using regression models to investigate the relative impact of acquisition factors on image quality and radiation dose

Objective: To investigate the optimum pelvis X-ray acquisition factors for a 10-year-old child. Secondly, to evaluate the impact of each acquisition factor on image quality (IQ) and radiation dose. Method: Images were acquired using a pelvis phantom and a range of acquisition parameters; e.g. tube potential, additional filtration and source-to-image distance (SID). Automatic exposure control (AEC) was used with two orientations (head towards/away from two outer chambers) and three different chamber selections. Visual IQ was evaluated using relative and absolute-VGA methods. Radiation doses were measured by placing a dosimeter on the anterior surface of the phantom. Regression analysis was used to determine optimum parameters. Results: The optimised technique (178.8 µGy), with diagnostic IQ, was with 89kVp, 130 cm SID and with 1 mm Al + 0.1 mm Cu filtration. This technique was with the head towards the two outer AEC chambers. Regression analysis showed that SID had the lowest impact on IQ (β = 0.002 95% CI −0.001 to 0.005) and dose (β = −0.96 95% CI −0.40 to −1.53). The impact of filtration on dose (β = −76.24 95% CI −86.76 to −85.72) was higher than tube potential (β = −13.44 95% CI −14.34 to −12.53). The following impact ratios were higher on IQ than radiation dose: filtration/kVp; 11.28 times, filtration/SID; 7.01 times and kVp/SID; 0.62 times. Conclusion: Optimised parameters were identified as 89 kVp, 130 cm SID and with 1 mm Al + 0.1 mm Cu additional filtration. Regression analysis demonstrated that filtration and tube potential had the greatest effect on radiation dose and IQ, respectively

Normative data of multifrequency tympanometry in rabbits

In an experimental study, we evaluated acoustic immittance in rabbits in order to use these data as normative values for further experimental investigations. This study is the first experimental evaluation of both conventional 226 Hz and multifrequency tympanometry (MFT) in rabbits. For the investigation, we used 33 female New Zealand rabbits weighing 3.2 - 4.4 kg and aged six months. Bilateral measurements using conventional 226 Hz and MFT were performed under general anaesthetic. A 226 Hz tympanogram was recorded for all animals by conducting an air pressure sweep from +200 to -400 daPa at a rate of 50 daPa/s. Subsequent tympanograms were recorded over a wide frequency range from 250 to 2000 Hz. The acoustic impedance device used in this study provided reproducible and evaluable tympanograms. The applied tone frequency of 226 Hz proved to be especially suitable for determining compliance. Normative data obtained from our study reveal the resonance frequency to be 1368±205 standard deviation (SD) for the right side and 1413±216 SD for the left side. The values for physiological acoustic immittance of the middle ear in the rabbit obtained here can serve as normative data in subsequent experimental animal studies. © Laboratory Animals Ltd