To stimulate bone regeneration, the design of bioactive implants is a great challenge in current orthopedic research. We reasoned that implants should be suitable both to stimulate osteogenic differentiation of mesenchymal stem cells and prevent infections at the site of implantation. Therefore, we focus on copper ions, which are known to exert antimicrobial effects. On the other hand, copper is essential for the cell physiology, including the formation of the extracellular matrix. We studied the influence of copper ions on mesenchymal stem cells at various concentrations and identified the limits of copper concentrations for cell survival. Below the critical concentration for cell survival we analysed proliferation and osteogenic differentiation of the cells in the presence of copper ions. We found that copper stimulated the proliferation of the mesemchymal stem cells at 0.1 mM. Osteogenic differentiation decreased after 14 days at a concentration of 0.05 - 0.1 mM copper ions in osteogenic medium measured by the expression of osteogenic proteins, like alkaline phosphatase (ALP), bone sialoprotein (BSP) and collagen I (COL). We argue that at the implant surface a higher concentration of copper could prevent biofilm formation of bacteria and physiological concentrations in the vicinity of the implant would stimulate stem cell expansion. Together, copper is an interesting agent to control both bacteria and stem cells in the field of implant technology.

Studies on bone cell ingrowth into synthetic, porous three-dimensional (3D) implants showed difficulties arising from impaired cellular proliferation and differentiation in the core region of these scaffolds with increasing scaffold volumein vitro. Therefore, we developed anin vitroperfusion cell culture module, which allows the analysis of cells in the interior of scaffolds under different medium flow rates. For each flow rate the cell viability was measured and compared with results from computer simulations that predict the local oxygen supply and shear stress inside the scaffold based on the finite element method. We found that the local cell viability correlates with the local oxygen concentration and the local shear stress. On the one hand the oxygen supply of the cells in the core becomes optimal with a higher perfusion flow. On the other hand shear stress caused by high flow rates impedes cell vitality, especially at the surface of the scaffold. Our results demonstrate that both parameters must be considered to derive an optimal nutrient flow rate.

Promising investigations on the selective killing of tumor cells were reported using cold atmospheric pressure plasma (CAP) in vitro. Pyruvate, a supplement in cell culture media, could protect cells against the action of reactive oxygen species. Here, we provide an overview of the in vitro studies concerning the selective killing of tumor cells by CAP with special emphasis on pyruvate concentration in the cell culture media. Several former studies were performed in media with different pyruvate content. Our cell experiments confirmed that pyruvate mitigates the action of the plasma‐activated medium on cells. Therefore, future in vitro studies should be done in media with similar pyruvate content.

Poly(L-lactide-co-D/L-lactide)-based fiber meshes resembling structural features of the native extracellular matrix have been prepared by electrospinning. Subsequent coating of the electrospun fibers with an ultrathin plasma-polymerized allylamine (PPAAm) layer after appropriate preactivation with continuous O₂/Ar plasma changed the hydrophobic nature of the polylactide surface into a hydrophilic polymer network and provided positively charged amino groups on the fiber surface able to interact with negatively charged pericellular matrix components. In vitro cell experiments using different human cell types (epithelial origin: gingiva and uroepithelium; bone cells: osteoblasts) revealed that the PPAAm-activated surfaces promoted the occupancy of the meshes by cells accompanied by improved initial cell spreading. This nanolayer is stable in its cell adhesive characteristics also afterγ-sterilization. An in vivo study in a rat intramuscular implantation model demonstrated that the local inflammatory tissue response did not differ between PPAAm-coated and untreated polylactide meshes.

Plasma-polymerized allylamine (PPAAm) coatings of titanium enhance the cell behavior of osteoblasts. The purpose of the present study was to evaluate a PPAAm nanolayer on zirconia after a storage period of 5 years. Zirconia specimens were directly coated with PPAAm (ZA0) or stored in aseptic packages at room temperature for 5 years (ZA5). Uncoated zirconia specimens (Zmt) and the micro-structured endosseous surface of a zirconia implant (Z14) served as controls. The elemental compositions of the PPAAm coatings were characterized and the viability, spreading and gene expression of human osteoblastic cells (MG-63) were assessed. The presence of amino groups in the PPAAm layer was significantly decreased after 5 years due to oxidation processes. Cell viability after 24 h was significantly higher on uncoated specimens (Zmt) than on all other surfaces. Cell spreading after 20 min was significantly higher for Zmt = ZA0 > ZA5 > Z14, while, after 24 h, spreading also varied significantly between Zmt > ZA0 > ZA5 > Z14. The expression of the mRNA differentiation markers collagen I and osteocalcin was upregulated on untreated surfaces Z14 and Zmt when compared to the PPAAm specimens. Due to the high biocompatibility of zirconia itself, a PPAAm coating may not additionally improve cell behavior.