Biocompatibility of Antimicrobial Ionic Dimethacrylates

Objectives: This study assessed the cytotoxic potential of antimicrobial ionic dimethacrylates: 2-(methacryloyloxy)-N-(2-(methacryloyloxy)ethyl)-N,N-dimethylethan-1-aminium (IDMA1) and N,N'-([1,1'-biphenyl]-2,2'-diylbis(methylene))bis(2-(methacryloyloxy)-N,N-dimethylethan-1-aminium) (IDMA2), and methacrylic acid (MA), a common degradation product.
Methods: Gingival fibroblasts (HGF) and mouse subcutaneous fibroblasts (ATCC®CCL-1™) were exposed to two-fold serial dilutions of IDMA1 (≤ 1.6 μmol), IDMA2 (≤ 0.86 μmol), or methacrylic acid (≤ 12 mM). The direct contact test was performed per ISO10993-5. After 24 and 72 h exposure, cells were assessed for viability and metabolic activity.
Results: HGFs and ATCC®CCL-1™ cells exhibited different sensitivities to the methacrylates. At given concentrations, IDMA1 did not significantly affect the viability of HGF cells while reducing the viability of ATCC®CCL-1™ cells (P≤0.05) in a concentration-dependent manner. In contrast, MA did not affect either viability or the metabolic activity of these cell lines at biologically relevant concentrations. Time of IDMA1 exposure significantly affected (P≤0.05) the metabolic activity of HGFs and ATCC®CCL-1™ cells: it was reduced ≥ 15% after 72 h incubation. In the IDMA2 series, the modest (~5%) reduction in metabolic activity of ATCC®CCL-1™ cells after 72 h exposure was not statistically significant.
Conclusions: Variances in cytotoxic potential of methacrylates between different cell lines accentuate the importance of employing biologically relevant cells in biocompatibility assessments. This effort underscores the importance of bio-testing prior to comprehensive physiochemical and mechanical testing to ensure that the antimicrobial agent’s potential cytotoxicity to mammalian cells is carefully balanced.