Functional implants between complex tissues are still an unsolved medical problem. Gradients along the implant could improve the situation at the tissue transition region. Besides gradients in the mechanical properties of the implant, the release of signaling proteins with spatial gradients would be a significant progress towards more functional implants. To generate such a gradient we use a combination of a nanoparticular drug release system and the Layer-by-Layer technology for immobilization. Biopolymers like chitosan or alginate can be used to prepare such nanoparticles for drug delivery applications. Our approach focusses on the incorporation of proteins, such as bone morphogenetic protein 2 (BMP-2) or transforming growth factor beta 3 (TGF-β 3) into the nanoparticles and the combination with polyelectrolytes such as alginate, chondroitin sulfate or hyaluronic acid in the LbL-technique to generate spatial gradients on a surface of an implant.
Nanoparticles were prepared by ionotropic gelation of chitosan and tripolyphosphate or alginate and Poly-l-lysine. The resulting particles were characterized via dynamic light scattering (DLS). Nanoparticle coatings were prepared by LbL using a dip-robot and alginate, chondroitin sulfate or hyaluronic acid as a polyanions. The resulting films were investigated by ellipsometry, atomic force microscopy (AFM) and scanning electron microscopy (SEM). Enzymatic degradation of the coatings was carried out at 37 °C in buffered solution and observed by ellipsometry.
Nanoparticles with a well-defined particle size and zetapotential have been obtained. The cationic nanoparticles were coated on silicon as a model surface by the LbL-method with different polyanions. A linear increase in layer thickness with the number dipping cycles is observed. Varying the dipping depth during the coating process resulted in a spatial concentration gradient on the silicon substrate. The degradation of the multilayer system has been proven by the decrease of the layer film thickness in lysozyme solution. BMP-2 was incorporated with high efficiency. Adapting the nanoparticle immobilization to electrospun fiber mats yields to promising results.