Base-metal dental casting alloy biocompatibility assessment using a human-derived three-dimensional oral mucosal model

Nickel–chromium (Ni–Cr) alloys used in fixed prosthodontics have been associated with type IV Ni-induced hypersensitivity. We hypothesised that the full-thickness human-derived oral mucosa model employed for biocompatibility testing of base-metal dental alloys would provide insights into the mechanisms of Ni-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 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 Ni. Co–Cr demonstrated significantly enhanced biocompatibility compared with Ni–Cr alloy-treated oral mucosal models. The human-derived full-thickness oral mucosal model discriminated between dental alloys and provided insights into the mechanisms of Ni-induced toxicity, highlighting potential clinical relevance.