INTRODUCTION: The treatment of severe brain related diseases, such as glioblastoma multiforme (GBM), requires innovative local therapeutic approaches. Magnesium (Mg) -based neural implants hold potential for local treatment, as they facilitate long-term, controlled drug and ion release due to their biodegradability. The present study characterizes cell-material interactions, focusing on the influence of GBM cell lines Mg degradation.
METHODS: Cell influence on Mg degradation was analyzed by semi-static immersion test. Mg discs were ground, cleaned, sterilized and pre-incubated in DMEM + 10% FBS. Subsequently, two human GBM cell lines (A172, LN229), treated or untreated with mitomycin C (MMC; proliferation inhibitor), and human astrocytes were seeded on Mg discs. Mg discs immersed in medium without cells were used as control. Immersion test was conducted for 6 days after pre-incubation. Removal of the degradation layer was carried out using chromic acid treatment. Scanning electron microscopy (SEM) and focused ion beam (FIB) cutting were employed for cross section analysis of the degradation layer.
RESULTS: MMC treatment of GBM cells led to significantly decreased degradation rates compared to Mg specimens seeded with untreated GBM cells and the control (no cells). Astrocytes exhibited no effect on the degradation rate. The mean degradation layer depth obtained from SEM/FIB analysis was revealed to be (a) lower for cell seeded Mg specimens compared to the control and (b) cell type independent.
DISCUSSION: The results suggest that cells influence Mg degradation through more complex (“active”) degradation mechanisms. Particularly, the enhanced proliferation, probably accompanied by increased excretion of metabolites (hallmarks of cancer cells), seem to majorly influence Mg degradation. Cancer cells are known to excessively excrete lactate due to their altered cellular respiration1. Further, the expression of some matrix metalloproteinases (MMPs)2 and extracellular matrix (ECM) components, such as hyaluronic acid (HYA)3, were found to be upregulated in GBM cells. The combination of locally lowered pH values, due to e.g. elevated lactate levels, altered degradation layers, due to digestion of ECM compounds by MMPs and excretion of new ECM molecules, might explain the underlaying degradation mechanisms. To verify this, analysis of lactate and MMP supernatant content, ECM composition, and composition and density of the degradation layers will be performed.