Biocompatibility effects of indirect exposure of base-metal dental casting alloys to a human-derived three-dimensional oral mucosal model.

OBJECTIVES: The study employed a three-dimensional (3D) human-derived oral mucosal model to assess the biocompatibility of base-metal dental casting alloys ubiquitous in fixed prosthodontic and orthodontic dentistry. METHODS: Oral mucosal models were generated using primary human oral keratinocyte and gingival fibroblast cells seeded onto human de-epidermidised dermal scaffolds. Nickel-chromium (Ni-Cr) and cobalt-chromium (Co-Cr) base-metal alloy immersion solutions were exposed to oral mucosal models for increasing time periods (2-72h). Analysis methodologies (histology, viable cell counts, oxidative stress, cytokine expression and toxicity) were performed following exposure. RESULTS: Ni-based alloy immersion solutions elicited significantly decreased cell viability (P<0.0004) with increased oxidative stress (P<0.0053), inflammatory cytokine expression (P<0.0077) and cellular toxicity levels (P<0.0001) compared with the controls. However, the Ni-free Co-Cr-based alloy immersion solutions did not elicit adverse oxidative stress (P>0.4755) or cellular toxicity (P<0.2339) responses compared with controls. CONCLUSIONS: Although the multiple analyses highlighted Ni-Cr base-metal alloy immersion solutions elicited significantly detrimental effects to the oral mucosal models, it was possible to distinguish between Ni-Cr alloys using the approach employed. The study employed a 3D human-derived full-thickness differentiated oral mucosal model suitable for biocompatibility assessment of base-metal dental casting alloys through discriminatory experimental parameters. CLINICAL SIGNIFICANCE: Increasing incidences of Ni hypersensitivity in the general population warrants serious consideration from dental practitioners and patients alike where fixed prosthodontic/orthodontic dental treatments are the treatment modality involved. The novel and analytical oral mucosal model has the potential to significantly contribute to the advancement of reproducible dental medical device and dental material appraisals.

Development of a discriminatory biocompatibility testing model for non-precious dental casting alloys.

OBJECTIVES: To develop an enhanced, reproducible and discriminatory biocompatibility testing model for non-precious dental casting alloys, prepared to a clinically relevant surface finishing condition, using TR146 oral keratinocyte cells. METHODS: Comparative biocompatibility was determined following direct and indirect exposure of TR146 cells to two nickel-chromium (Ni-Cr) and a cobalt-chromium (Co-Cr) alloy-discs. The surface roughness of the discs was determined using a contact stylus profilometer and the elemental ion release by inductively coupled plasma mass spectrometry (ICP-MS). Subsequent biocompatibility analysis included cell morphology, cell density measurements with Trypan blue exclusion assay, inflammatory cytokine expression with ELISAs, cellular metabolic activity using XTT and cellular toxicity using lactate dehydrogenase (LDH) release assay. RESULTS: TR146 cell morphology was altered following direct and indirect exposure to the Ni-Cr alloys but not the Co-Cr alloy. Significant reductions (all P<0.001) in viable cell density measurements, cellular metabolic activity, significant increases inflammatory cytokine expression and cellular toxicity were observed when TR146 cells were exposed to the Ni-Cr alloys. Significant decreases in cell density measurements, cellular metabolic activity, significant increases inflammatory cytokine expression and cellular toxicity for the Ni-Cr d.Sign(®)15 alloy compared with d.Sign(®)10 alloy were identifiable (all P<0.001). Cellular toxicity was attributed to nickel ion release levels in solution detected by ICP-MS analysis. DISCUSSION: Nickel ions from the Ni-Cr alloys permeated the epithelial cells and activated a proinflammatory response, namely IL-1a, IL-8 and PGE2 expression. Further evidence of nickel ioninduced cell death was supported by the decreased biocompatibility of the highest nickel ion releasing alloy (d.Sign(®)15 compared with d.Sign(®)10) and the increased biocompatibility of the Co-Cr (d.Sign(®)30) alloy where nickel ions were absent.