Synergistic effects of biodegradable magnesium alloy and erythromycin on osteogenic activity

Biodegradable magnesium (Mg)-based alloys are emerging as promising alternatives to non-resorbable titanium for bone regeneration because of their favorable mechanical properties and biodegradability. However, the interaction between Mg alloys and immunomodulatory agents in promoting osteogenesis remains poorly understood. This study aimed to evaluate the osteogenic effects of an Mg alloy on pre-osteoblasts and to investigate whether erythromycin enhances Mg-induced osteogenic differentiation through regulation of developmental endothelial locus-1 (DEL-1).

WE43 Mg alloy disks were immersed in culture medium to produce Mg alloy-conditioned medium at concentrations of 25%, 50%, 75%, and 100%. MC3T3-E1 cells were treated with conditioned medium alone or combined with erythromycin (20 μg/mL). Cell viability was assessed using the MTT assay. Osteogenic differentiation was evaluated by Alizarin Red S staining (ARS), quantitative PCR analysis of osteogenic markers (Runx2, Sp7, Bglap, Edil3), and Western blot analysis of DEL-1 expression.

WE43 Mg alloy showed no cytotoxic effects on MC3T3-E1 cells. Treatment with Mg alloy-conditioned medium significantly enhanced osteogenic differentiation and extracellular matrix mineralization. The strongest osteogenic response was observed in cells receiving combined WE43 Mg alloy and erythromycin treatment. DEL-1 expression was significantly upregulated at both mRNA and protein levels in Mg alloy-treated groups, accompanied by increased expression of osteogenic markers. These effects were further amplified by erythromycin supplementation.

WE43 Mg alloy promotes osteogenic differentiation of MC3T3-E1 cells, and erythromycin synergistically enhances this effect, potentially via DEL-1 upregulation. These findings support the combined use of immunomodulatory agents and Mg-based biomaterials in regenerative dentistry.