Base-metal dental casting alloy biocompatibility assessment using a human-derived 3D oral mucosal model

Abstract

Nickel-chromium (Ni-Cr) alloys used in fixed prosthodontics have been associated with type IV nickel-induced hypersensitivity. We hypothesized the full-thickness human-derived oral mucosa model employed for biocompatibility testing of base-metal dental alloys would provide insights into mechanisms of nickel-induced toxicity. Primary oral keratinocytes and gingival fibroblasts were seeded onto Alloderm™ and maintained until full-thickness was achieved prior to Ni-Cr and cobalt-chromium (Co-Cr) alloy-disc exposure (2-72 h). Biocompatibility assessment involved histological analyses with cell viability measurements, oxidative stress responses, inflammatory cytokine expression and cellular toxicity analyses. Inductively coupled plasma mass spectrometry (ICP-MS) analysis determined elemental ion release levels. We detected adverse morphology with significant reductions in cell viability, significant increases in oxidative stress, inflammatory cytokine expression and cellular toxicity for the Ni-Cr alloy-treated oral mucosal models compared with untreated oral mucosal models and adverse effects were increased for the Ni-Cr alloy that leached the most nickel. Co-Cr demonstrated significantly enhanced biocompatibility compared with Ni-Cr alloy-treated oral mucosal models. The human-derived full-thickness oral mucosal model was discriminatory between dental alloys and mechanistically provided insights into Ni-induced toxicity, highlighting potential clinical relevance.