Titanium Activates the DNA Damage Response Pathway in Oral Epithelial Cells: A Pilot Study

Purpose: To evaluate the effect of titanium (Ti) particles on oral epithelial cell homeostasis and the potential of dental implants to release Ti debris upon insertion. Materials and Methods: Dental implants with varying surface treatments were employed to determine the feasibility of particle release during implant placement as well as the impact of free Ti debris on oral epithelial cells. Ti particles derived from implant surfaces were isolated and cultured in direct contact with normal oral epithelial cells for 48 hours. Further, cells were fixed and processed for immunofluorescence assay to detect the activation of the DNA damage response (DDR) using CHK2 and BRCA1 molecular markers. Positive cells demonstrating DNA damage were quantified and statistically analyzed. Results: Ti particles derived from implants containing phosphate-enriched titanium oxide (PETO), fluoride-modified (FM), and grit-blasted (GB) surface treatments were able to activate CHK2 and trigger the recruitment of BRCA1 in oral epithelial cells. Also, implants with GB surfaces were able to release Ti particles upon implant placement. Conclusion: The results indicate that Ti debris may be detached from the implant surface upon placement. Also, free Ti particles can trigger DDR signaling in oral epithelial cells. These findings suggest that Ti particles/debris released into a surgical wound may contribute to the disruption of epithelial homeostasis, and potentially compromise the oral epithelial barrier.