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 mg cm À2 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.

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. Key learning pointsThe way from clinical problems to improved implant materials: materials development, in vitro and in vivo testing. Establishment of mesoporous thin silica films on ceramic surfaces. Degradation of mesoporous silica films in physiological medium. Implant-carried mesoporous silica films as drug delivery systems. Implant-based delivery of biomolecules using mesoporous silica coatings.

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