Evaluation of the immunomodulatory effects of cobalt, copper and magnesium ions in a pro inflammatory environment

Biomaterials and scaffolds for Tissue Engineering are widely used for an effective healing and regeneration. However, the implantation of these scaffolds causes an innate immune response in which the macrophage polarization from M1 (pro-inflammatory) to M2 (anti-inflammatory) phenotype is crucial to avoid chronic inflammation. Recent studies have showed that the use of bioactive ions such as cobalt (Co(2+)), copper (Cu(2+)) and magnesium (Mg(2+)) could improve tissue regeneration, although there is limited evidence on their effect on the macrophage response. Therefore, we investigated the immunomodulatory potential of Co(2+), Cu(2+) and Mg(2+) in macrophage polarization. Our results indicate that Mg(2+) and concentrations of Cu(2+) lower than 10 μM promoted the expression of M2 related genes. However, higher concentrations of Cu(2+) and Co(2+) (100 μM) stimulated pro-inflammatory marker expression, indicating a concentration dependent effect of these ions. Furthermore, Mg(2+) were able to decrease M1 marker expression in presence of a mild pro-inflammatory stimulus, showing that Mg(2+) can be used to modulate the inflammatory response, even though their application can be limited in a strong pro-inflammatory environment.