Abstract
Magnesium alloys have recently gained increasing attention for biomedical applications due to their unique biodegradation and biocompatibility profiles. However, investigations of the interactions between magnesium alloy degradation byproducts and host immune cells (particularly macrophages) are still relatively unexplored. Here, we study the interaction between degradation byproducts and macrophage response in vitro. An extract-based in vitro study was developed to examine macrophage response to different degradation byproducts formed at various time points of the corrosion process when a magnesium alloy is degraded in HBSS. Magnesium and non-degradable titanium alloy wires (current industry standard) were immersed in HBSS and incubated for 5 and 15 days to generate degradation byproducts. THP-1 human monocytic cells were treated with 10% extract-RPMI medium for 24 and 72 hours, followed by RNA extraction and qPCR analysis to investigate the effects of degradation byproduct formation. Macrophages that were exposed to the extract from magnesium wire and incubated for 5 days showed a transient pro-inflammatory response at early time-points, evidenced by increased expression of IL-1β at 24 hours and the switch towards an anti-inflammatory phenotype by 72 hours with elevated expression of CD206 and CD163, and decreased expression of NOS2. On the other hand, the 15-day magnesium extract generated a strong early pro-inflammatory (elevated IL-1β) response at 24 hours but induced a reparative process by 72 hours. Comparison of pro-inflammatory response associated with titanium extracts and at various degradation time points revealed consistent increases in IL-1β while anti-inflammatory IL-10 and IL-4 were minimally activated, indicating sustained pro-inflammatory activity surrounding titanium extracts. These findings highlights the transient nature of the macrophage responses to magnesium degradation byproducts, as magnesium alloy induced macrophages exhibit an initial pro-inflammatory phase with subsequent reparative activation. The distinct pro-inflammatory (M2) response from titanium contrasts with the results for magnesium which releases anti-inflammatory and anti-fibrosing agents for about 3 weeks. These results provide more evidence towards the potential benefits of using magnesium alloys as biodegradable implants.
