Magnesium-lithium thin films for neurological applications-An in vitro investigation of glial cytocompatibility and neuroinflammatory response

Lithium (Li), a widely used drug for bipolar disorder management, is associated with many side effects due to systemic exposure. The localized delivery of lithium through implants could be an approach to overcome this challenge, for which biodegradable magnesium (Mg)-based materials are a promising choice. In this study, we focus on Mg-Li thin film alloys as potential Li-releasing implants. Therefore, we investigated the in vitro short-term corrosion behavior and cytocompatibility of two alloys, Mg-1.6wt%Li and Mg-9.5wt%Li. As glial cells are the key players of foreign body responses to implants, we used human glial cell lines for cytocompatibility studies, and a murine brain slice model for a more holistic view at the neuroinflammatory response. We found that Mg-1.6wt%Li corrodes approximately six times slower than Mg-9.5wt%Li. Microscopic analysis showed that the material surface (Mg-1.6wt%Li) is suitable for cell adhesion. The cytocompatibility test with Mg-1.6wt%Li and Mg-9.5wt%Li alloy extracts revealed that both cell types proliferated well up to 10 mM Mg concentration, irrespective of the Li concentration. In the murine brain slice model, Mg-1.6wt%Li and Mg-9.5wt%Li alloy extracts did not provoke a significant upregulation of glial inflammatory/ reactivity markers (IL-1 beta , IL-6, FN1, TNC) after 24 h of exposure. Furthermore, the gene expression of IL-1 beta (up to 3-fold) and IL-6 (up to 16-fold) were significantly downregulated after 96 h, and IL-6 downregulation showed a Li concentration dependency. Together, these results indicate the acute cytocompatibility of two Mg-Li thin film alloys and provide basis for future studies to explore promising applications of the material.