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.

Nanoporous (or mesoporous) silica materials have been extensively investigated as a novel biomaterial in the last few years, especially with regard to bone tissue engineering. Due to their high specific surface areas, capability for chemical modification, and their large pore volumes, nanoporous silica nanoparticles (NPSNPs) are of tremendous interest as drug delivery systems. In this study, we describe the immobilization of the bone growth factor BMP2 on NPSNPs in biologically relevant amounts, using coupling via an aminosilane linker. The amount of BMP2 loaded onto NPSNPs was determined using two different methods. The biocompatibility of NPSNPs was tested with different cell lines upon exposure to different particle concentrations. Whereas standard cell types (HepG2, NIH3T3) are relatively insensitive against NPSNPs, adMSC cells (adipose-derived human mesenchymal stem cells) show a somewhat reduced viability. adMSC cells were also used to test for the osteoinductive effect of the BMP2-carrying NPSNPs. Histological staining reveals the osteogenic differentiation of the human mesenchymal stem cells. Even BMP-free amino-modified NPSNPs show a certain osteoinductive effect, which is however significantly stronger with immobilized BMP2 and can furthermore be enhanced by supplemental dexamethasone. We therefore suggest that NPSNPs carrying BMP2 are suitable for application in bone tissue engineering, e.g. in the construction of scaffolds.

BackgroundIn orthopaedic surgery, accumulation of agents such as anti-infectives in the bone as target tissue is difficult. The use of magnetic nanoparticles (MNPs) as carriers principally enables their accumulation via an externally applied magnetic field. Magnetizable implants are principally able to increase the strength of an externally applied magnetic field to reach also deep-seated parts in the body. Therefore, the integration of bone-addressed therapeutics in MNPs and their accumulation at a magnetic orthopaedic implant could improve the treatment of implant related infections. In this study a martensitic steel platelet as implant placeholder was used to examine its accumulation and retention capacity of MNPs in an in vitro experimental set up considering different experimental frame conditions as magnet quantity and distance to each other, implant thickness and flow velocity.ResultsThe magnetic field strength increased to approximately 112% when a martensitic stainless steel platelet was located between the magnet poles. Therewith a significantly higher amount of magnetic nanoparticles could be accumulated in the area of the platelet compared to the sole magnetic field. During flushing of the tube system mimicking the in vivo blood flow, the magnetized platelet was able to retain a higher amount of MNPs without an external magnetic field compared to the set up with no mounted platelet during flushing of the system. Generally, a higher flow velocity led to lower amounts of accumulated MNPs. A higher quantity of magnets and a lower distance between magnets led to a higher magnetic field strength. Albeit not significantly the magnetic field strength tended to increase with thicker platelets.ConclusionA martensitic steel platelet significantly improved the attachment of magnetic nanoparticles in an in vitro flow system and therewith indicates the potential of magnetic implant materials in orthopaedic surgery. The use of a remanent magnetic implant material could improve the efficiency of capturing MNPs especially when the external magnetic field is turned off thus facilitating and prolonging the effect. In this way higher drug levels in the target area might be attained resulting in lower inconveniences for the patient.