Cell-related influences on the degradation of magnesium-based materials for neural applications
The use of magnesium (Mg)-based materials for medical devices has been promoted over the past years, owing to their excellent biocompatibility and degradability under physiological conditions. Apart from the widely discussed applications in orthopedics, Mg and its alloys are also promising materials to be applied in local strategies for the treatment of severe neurological disorders. Considering the functional importance and sensitivity of the human brain, the evaluation of Mg-based materials for neural applications requires careful in vitro assessment. Such an analysis includes cytocompatibility tests, as well as the elucidation of cell-induced degradation mechanisms to predict the in vivo material performance. In the present thesis, the impact of different neural cell types (tumor cells, astrocytes and microglial cells) and densities on the degradation of Mg discs and magnetron sputtered Mg-based thin films was investigated in a direct contact in vitro model (i.e., cells directly cultured onto the material surface). In the first part of the thesis, the specific cell-induced degradation mechanisms were analyzed for the cell contact on pure Mg discs. The cell impact on Mg degradation was quantified using immersion tests for weight loss measurement, scanning electron microscopy (SEM) and infrared (IR) spectroscopy methods. Cell distribution, cell metabolic activity, extracellular matrix (ECM) composition and distribution, and the chemical interaction of selected ECM molecules with Mg were investigated to shed light on the underlying cell-related degradation mechanisms. The degradation analysis revealed cell type- as well as cell-density dependent degradation behavior. Degradation inhibition was observed for none-proliferating neural cells and was related to the presence of a passivating layer of cells and ECM and to the formation of stable carbonate-rich degradation layers. Cell metabolic activity, and as a consequence thereof the local pH decrease, was identified to play a crucial role in degradation promotion. Moreover, the ECM glycosaminoglycan (GAG) compounds chondroitin sulfate (CS) and hyaluronic acid (HA) were shown to affect degradation by the complexation of either Mg2+ or Ca2+ and PO43-. Finally, the results obtained in this thesis indicated a cell-induced time dependence of the degradation outcome for Mg materials in contact with neural cells. In the second part of the thesis, Mg-based thin films were analyzed regarding their stability under in vitro testing conditions and hence suitability for neural applications. Thin film stability was assessed in immersion tests. A preliminary thin film cytotoxicity analysis was conducted employing a cell viability and cytoskeleton staining in contact with Mg-6Ag thin films with different degradation rates. Pure Mg as well as Mg-6Ag thin films proved to be sufficiently stable under in vitro conditions for a time span of four days and therefore qualified for further in-depth in vitro analysis. The preliminary cytotoxicity screening showed that degradation rate tailoring of Mg-based thin films may be a promising tool for customized approaches to the treatment of different neurological disorders.
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