Assessment of ion release, cytotoxicity, and potential systemic toxicity of titanium dental alloy

Titanium (Ti-6Al-4 V) alloys are widely utilized in dental and orthopedic implants for their strength, corrosion resistance, and biocompatibility. However, the oral environment's corrosive conditions can promote ion release, raising concerns regarding potential long-term public health risks. In this investigation, samples of titanium alloy were submerged in artificial saliva for six months to simulate long-term oral exposure. The concentrations of corrosion derived metal ions were subsequently determined using Inductively Coupled Plasma Mass Spectrometry. Cytotoxicity, inflammatory, and apoptotic responses were assessed in fibroblast cell lines. Additionally, an in vivo study in male mice assessed systemic oxidative stress, antioxidant defense mechanisms, and liver and kidney function. Titanium alloy released ions treated cells showed a marked decline in fibroblast viability and a significant elevation (p < 0.05) in pro-apoptotic and inflammatory markers, including Bax, TNF-α, and IL-6, compared with untreated cells. In vivo findings demonstrated significant increases in TBARS and DNA fragmentation, accompanied by a depletion of antioxidant enzymes, particularly in renal tissues. Biochemical evaluation of serum samples demonstrated significant changes in lipid profiles and marked impairments in liver and kidney function. Histopathological assessments confirmed these findings, showing inflammatory infiltration and degenerative changes in hepatic and renal tissues. Overall, ions released from the titanium alloy induced pronounced cytotoxicity accompanied by increased oxidative imbalance and inflammatory reactions, emphasizing the need for developing safer biomaterials and implementing long-term patient monitoring to mitigate chronic complications.